[ { "id": "authors:z4z2h-01p79", "collection": "authors", "collection_id": "z4z2h-01p79", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191022-104814157", "type": "article", "title": "Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures", "author": [ { "family_name": "Martinez-Camarillo", "given_name": "Juan-Carlos", "clpid": "Martinez-Camarillo-J-C" }, { "family_name": "Spee", "given_name": "Christine K.", "clpid": "Spee-C-K" }, { "family_name": "Chen", "given_name": "Michael", "clpid": "Chen-Michael" }, { "family_name": "Rodriguez", "given_name": "Anthony", "clpid": "Rodriguez-A" }, { "family_name": "Nimmagadda", "given_name": "Kiran", "clpid": "Nimmagadda-K" }, { "family_name": "Trujillo-Sanchez", "given_name": "Gloria Paulina", "clpid": "Trujillo-Sanchez-G-P" }, { "family_name": "Hinton", "given_name": "David R.", "clpid": "Hinton-D-R" }, { "family_name": "Giarola", "given_name": "Alessandra", "clpid": "Giarola-A" }, { "family_name": "Pikov", "given_name": "Victor", "clpid": "Pikov-V" }, { "family_name": "Sridhar", "given_name": "Arun", "clpid": "Sridhar-A" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Weitz", "given_name": "Andrew C.", "clpid": "Weitz-A-C" } ], "abstract": "Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina. \n\nMethods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation. \n\nResults: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-\u03b1 levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency. \n\nConclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye.", "doi": "10.1167/iovs.18-25613", "issn": "1552-5783", "publisher": "Association for Research in Vision and Ophthalmology", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2019-10", "series_number": "13", "volume": "60", "issue": "13", "pages": "4303-4309" }, { "id": "authors:n26nc-v4f73", "collection": "authors", "collection_id": "n26nc-v4f73", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191031-114840016", "type": "article", "title": "Recovery of retinal oxygenation after MEMS implant activation", "author": [ { "family_name": "Martinez", "given_name": "Juan Carlos", "clpid": "Martinez-J-C" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N-E" }, { "family_name": "Cook", "given_name": "Colin A.", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C-A" }, { "family_name": "Gonzalez-Calle", "given_name": "Alejandra", "clpid": "Gonzalez-Calle-A" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Purpose: Retinal ischemia due to diabetic retinopathy or retinal vascular occlusions is the leading cause of blindness worldwide. Although, the underlying pathophysiology from each condition is different, the common end results are: inner retinal hypoxia and ischemia. Changes associated with retinal hypoxia include the simultaneous activation of different pathways including inflammatory, aerobic and anaerobic metabolic response. Supplementing intravitreal oxygen has been demonstrated as a novel option in preliminary reports. Our implantable MEMS oxygenator drivesoxygen from the sub-conjunctival space to the proximity of the inner retina. The main objective of this study is to determine the efficacy of the oxygenation therapy in an ischemic animal model.\nMethods: Nine eyes from six pigmented rabbits were included, split evenly between either healthy, implant-treated or non-treated groups. Retinal vein occlusion (RVO) was created in all animals from treated and non-treated groups 3 days prior to surgical implantation and activation of the oxygenator. Continuous measurements of pO2 levels were performed next to the diffuser and retinal vessels using an oxygen probe controlled by a micromanipulator and monitored under indirect ophthalmoscopy. Eyes were then enucleated and the retina was peeled off and cryogenically preserved in liquid nitrogen for subsequent analysis of protein expression.\nResults: RVO was confirmed in all animals immediately after the procedure and remained occluded over the experiment. Oxygenator devices were successfully implanted without complications. In the treated group, oxygen levels increased progressively after a couple of minutes of activation and remained over 15 mmHg and 100 mmHg respectively (Figure 1A). For the non-treated group, pO\u2082 levels did not increase at the retina or nearby the device (below 5mmHg). Changes among protein expression and ratio (upregulation on NFkB and PDH; down-regulation of HIF1a, NFkB/IKKa ratio and P-PDH/PDH ratio) were observed in the treated group (Figure 1B-C).\nConclusions: The MEMS oxygenator device can be safely implanted into the eye. This study supports the feasibility of intravitreal oxygen delivery for treatment of ischemic retinal diseases through inflammatory response modulation. Future experiments will evaluate long-term efficacy.", "issn": "0146-0404", "publisher": "Lippincott, Williams & Wilkins", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2019-07", "series_number": "9", "volume": "60", "issue": "9", "pages": "Art. No. 3344" }, { "id": "authors:z1kb7-m8q52", "collection": "authors", "collection_id": "z1kb7-m8q52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191031-140439364", "type": "article", "title": "Toxicity of Transition Metal Complex-based Nanophotoswitches in Retina", "author": [ { "family_name": "Yue", "given_name": "Lan", "clpid": "Yue-Lan" }, { "family_name": "Shi", "given_name": "Yi", "orcid": "0000-0002-1981-8350", "clpid": "Shi-Yi" }, { "family_name": "Lin", "given_name": "Tai-Chi", "clpid": "Lin-Tai-Chi" }, { "family_name": "Pribisko", "given_name": "Melanie", "clpid": "Pribisko-M-A" }, { "family_name": "Grubbs", "given_name": "Robert", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Gray", "given_name": "Harry", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Chow", "given_name": "Robert", "clpid": "Chow-Robert" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Purpose: Nanophotoswitches (NPSs) based on transition metal complexes offer a new tool for optical stimulation of neural activity in photoreceptor degenerated retina. We previously reported robust light-elicited neural activity in degenerate retinae exposed to ruthenium bipyridine based NPSs (Rubpy-C17) and its iridium analog (Irbpy-C17). Irbpy-C17 was developed as an alternative to Rubpy-C17 for the biosafety properties of the iridium complexes. Here we present a study of the toxicity of both NPSs in rodent retinae.\nMethods: Toxicity of Rubpy-C17 was tested in wildtype C57BL/6J mice and Irbpy-C17 in wildtype Long Evans rats. Animals were intravitreally injected with the test molecules (up to 50 \u00b5M) and sacrificed at different time points post injection: 3, 7, 14 and 28 days, respectively. Retinae were obtained, fixed and sliced for histological analysis immediately after animal euthanization. H&E staining was performed to examine morphological integrity of retina and TUNEL staining performed to detect apoptosis of retinal cells. For comparison, Ru(bpy)3]Cl2 injection and sham surgery were included for control.\nResults: H&E staining revealed no detectable sign of morphological or structural changes in the retinae after prolonged exposure to either Rubpy-C17 or Irbpy-C17 versus the control. There was no significant reduction in the thickness of different nuclear and plexiform retinal layers or the density of retinal neurons (p<0.05), nor was there evidence of significant aggregation of immune cells. TUNEL staining showed minimal occurrence of cell apoptosis in the NPS treated retinae, similar to the control (p<0.05). No longitudinal changes in either the morphology or the cell apoptosis was observed with the post injection time.\nConclusions: Overall our data did not find ocular toxicity associated with either the ruthenium or the iridium based NPSs within the concentration range tested. The results obtained with both complexes are similar to that obtained with the control molecule [Ru(bpy)3]Cl2, which lacks a membrane-anchoring 17 carbon chain attached to the bipyridine group, indicating that the inclusion of the carbon chain did not enable NPSs entry into the cells, nor did it cause apoptotic response. The present study provides new evidence of biosafety of our NPSs in rodent retinae, further encouraging developing NPS-based molecular retinal prosthesis to potentially restore high-acuity prosthetic vision in the blind.", "issn": "0146-0404", "publisher": "Lippincott, Williams & Wilkins", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2019-07", "series_number": "9", "volume": "60", "issue": "9", "pages": "Art. No. 4987" }, { "id": "authors:qkhw3-00p28", "collection": "authors", "collection_id": "qkhw3-00p28", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191025-124827181", "type": "book_section", "title": "Wireless Implantable Intraocular Pressure Sensor with Parylene-Oil-Encapsulation and Forward-Angled RF Coil", "book_title": "2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems (MEMS)", "author": [ { "family_name": "Shapero", "given_name": "Aubrey", "clpid": "Shapero-A-M" }, { "family_name": "Agarwal", "given_name": "Abhinav", "clpid": "Agarwal-A" }, { "family_name": "Martinez", "given_name": "Juan Carlos", "clpid": "Martinez-J-C" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents a wireless and implantable intraocular pressure (IOP) sensor with parylene-oil-encapsulation packaging using a novel folded PCB architecture accomplishing practical RF coupling for power and data in a rabbit. The sensor is operated with an air gap of 5 mm between the primary coil and the animal, coupling to an on-chip coil at an input power of 32 dBm at 915 MHz, and can also be operated when the eyelid covers the sensor. Additionally, two novel results for parylene-on-oil deposition in general are presented. First, we show that the thickness of the porous layer of parylene-C (PA-C) and parylene-HT (PA-HT) deposited on silicone oils have a logarithmic decrease in porous layer thickness (PLT) versus silicone oil molecular weight (MW) over a range of 2\u2013139 kDa. Second, we directly verify that parylene-oil-encapsulated pressure sensors retain sensitivity despite material buildup for the first time.", "doi": "10.1109/memsys.2019.8870787", "isbn": "9781728116105", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2019-01", "pages": "21-24" }, { "id": "authors:vb52y-wxr39", "collection": "authors", "collection_id": "vb52y-wxr39", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180926-125050352", "type": "article", "title": "Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina", "author": [ { "family_name": "Pribisko", "given_name": "Melanie", "clpid": "Pribisko-M-A" }, { "family_name": "Herget", "given_name": "Uli", "orcid": "0000-0002-4419-1414", "clpid": "Herget-U" }, { "family_name": "Yue", "given_name": "Lan", "clpid": "Yue-Lan" }, { "family_name": "Lin", "given_name": "Ming-yi", "clpid": "Lin-Ming-Yi" }, { "family_name": "Chow", "given_name": "Robert H.", "clpid": "Chow-Robert-H" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Gray", "given_name": "Harry", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "abstract": "Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine (Rubpy)-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light illumination. We wish to optimize delivery, efficacy and biosafety of the NPSs; our preliminary experiments examining the Rubpy complexes in vivo suggest low acute toxicity. Intravitreal delivery of the Rubpy-C17 complexes has been shown to restore light response recorded from the superior colliculus of the photoreceptor degenerate RCS rats 1 day after the injection. The restored light response was largely preserved 3 days after the injection, suggesting that the Rubpy-C17 complexes are well tolerated by the retinal neurons during the test period.\n\nMethods : Promising NPSs molecules absorb and can be visualized by their luminescence upon visible wavelength illumination. This enables us to evaluate the toxicity of the NPSs using an array of in vitro, in vivo and ex vivo tests, including in vitro electrochemical and spectroscopic studies to determine DNA binding and DNA intercalation. In addition, the NPSs were embedded in polymer matrices and the emission monitored to determine the rate of release upon injection into the eye.\n\nResults : Preliminary data show that young zebrafish tolerate injection of up to 100 uM Rubpy-C17 into the eye, with complete disappearance of the Rubpy-C17 emission from the eye within a day. Interestingly, blue-green emission appears in the liver region as the orange-red emission of Rubpy-C17 decreases. As this may be a result of metabolism of the Rubpy-C17, we extracted the blue-green emitting molecule for characterization. Initial studies of slow-release drug delivery system and conditions indicate some success with polyethyleneglycol-poly(lactic-co-glycolic acid)-poly-L-lysine (PEG-PLGA-PEG) and polycaprolactone (PCL) polymers.\n\nConclusions : Our data suggest that NPSs dissolved in a DMSO solution and intravitreally administered remain stable and active in the ocular environment up to at least one day post injection, which can be extended when coadministered with certain polymer mixtures. The DNA binding and DNA intercalation studies, in combination with the extended release polymers, address toxicity concerns of the NPSs in the eye.", "issn": "0146-0404", "publisher": "Association for Research in Vision and Ophthalmology (ARVO)", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2018-07", "series_number": "9", "volume": "59", "issue": "9", "pages": "Art. No. 232" }, { "id": "authors:jac3d-ay287", "collection": "authors", "collection_id": "jac3d-ay287", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181010-142930931", "type": "article", "title": "Activity of iridium pyridine-based nanophotoswitches in retina", "author": [ { "family_name": "Yue", "given_name": "Lan", "clpid": "Yue-Lan" }, { "family_name": "Pribisko", "given_name": "Melanie", "clpid": "Pribisko-M-A" }, { "family_name": "Lin", "given_name": "Ming-yi", "clpid": "Lin-Ming-Yi" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Gray", "given_name": "Harry", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Chow", "given_name": "Robert H.", "clpid": "Chow-Robert-H" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light exposure. Compared with the ruthenium complexes, the family of iridium complexes has been more widely used in clinics, owing to its biosafety profile. We have thus synthesized and tested Irbpy-C17, an analog of Rubpy-C17 with the ruthenium core replaced by iridium.\n\nMethods : Rubpy molecules can be visualized by their luminescence upon visible wavelength illumination. To examine membrane incorporation, fluorescence imaging of HEK cells was obtained after incubation with Irbpy-C17. Activity of Irbpy-C17 was studied by MEA recording from wholemount retina after intravitreal injection. The test molecules were administered into the vitreous of blind RCS rats at the concentration of 200 \u00b5M. Animals were kept in dark after injection until the surgical dissection of retina. Acutely isolated retina was mounted on the MEA with the ganglion cell layer facing down to capture the spiking activity in response to light stimuli.\n\nResults : Irbpy-C17 exhibited good membrane incorporation similar to that of Rubpy-C17. Interestingly, despite that Irbpy-C17 elicited minimal light response initially, subsequent application of synaptic blocker cocktail that pharmacologically isolated RGCs substantially enhanced the light activation of RGCs (1.8 \u00b1 0.3 fold increase in spike frequency). In comparison with the 3-hour incubation between injection and dissection, prolonged 24-hour incubation led to a more pronounced 2.5 \u00b1 0.5 fold increase in spike frequency.\n\nConclusions : Our data suggest that Irbpy-C17 may act on multiple components of the retinal neural circuitry that could suppress its direct action on RGCs via synaptic transmission. These molecules intravitreally administered remain stable and active in the ocular environment up to at least one day post injection. These data will prompt us to further study the iridium complexes in parallel with the ruthenium counterparts, particularly for the underlying mechanism of their differential behavior. The NPSs obviates the need for gene manipulation or toxic UV illumination, highlighting its potential in generating high-acuity prosthetic vision in the blind.", "issn": "0146-0404", "publisher": "Association for Research in Vision and Ophthalmology", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2018-07", "series_number": "9", "volume": "59", "issue": "9", "pages": "Art. No. 3976" }, { "id": "authors:1mnx1-d0p02", "collection": "authors", "collection_id": "1mnx1-d0p02", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180926-123802831", "type": "article", "title": "Precision Wireless Implantable Continuous Intraocular Pressure Sensors Utilizing Parylene-on-oil Encapsulation", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Shapero", "given_name": "Aubrey", "clpid": "Shapero-A-M" }, { "family_name": "Agarwal", "given_name": "Abhinav", "clpid": "Agarwal-A" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Purpose : To demonstrate the precision of a first of its kind fully implantable continuous wireless pressure sensor that measures true intraocular pressure (IOP) and leverages commercially fabricated microelectromechanical (MEMS) components with embedded temperature compensation to ensure superb reliability.\nMethods : The continuous IOP sensor, with a form factor similar to an aqueous shunt, is designed to be implanted with the electronics in the superotemporal or inferotemporal subtenon's space with a flexible 23-gauge silicone tube permanently inserted into the anterior chamber or the pars plana. It consists of a parylene-on-oil packaged LPS25H MEMS barometer with temperature compensation (STMicroelectronics, Geneva, Switzerland), capacitors, and a custom designed integrated circuit, all assembled on a flexible polyimide substrate. Devices were tested on the benchtop. Ex vivo porcine eyes were vitrectomized, and the IOP sensor tube placed into the pars plana through one of the sclerotomies. The IOP was varied using the pressure setting on the vitrector, and resultant pressure readings from the sensor were analyzed.\nResults : Photographs of the fabricated device are shown in Fig. 1(a-b).1 In air, the wireless device has demonstrated 0.17 mmHg pressure sensitivity. Accelerated-lifetime saline soak testing of the packaged barometer itself has demonstrated stability for an extrapolated 20 months to date. A photograph of the ex vivo wireless porcine eye setup is shown in Fig. 1c. In addition to excellent precision during IOP sweeps, a step from 5 to 75 resulted in a 69.92 mmHg change as measured by the sensor (Fig. 2). A slow ramp down after changing the setting on the vitrector back to 5 mmHg is seen because the eye is essentially a closed system.\nConclusions : A breakthrough wireless IOP sensor has been realized utilizing a commercially fabricated barometer and a custom integrated circuit as its backbone. All testing to date, including ex vivo porcine data, demonstrates superior reliability and precision.", "issn": "0146-0404", "publisher": "Association for Research in Vision and Ophthalmology (ARVO)", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2018-07", "series_number": "9", "volume": "59", "issue": "9", "pages": "Art. No. 1997" }, { "id": "authors:razj3-9g325", "collection": "authors", "collection_id": "razj3-9g325", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181010-144747080", "type": "article", "title": "Effectiveness and Safety of a phototherapeutic contact lens for Diabetic Retinopathy", "author": [ { "family_name": "Yang", "given_name": "Qianhui", "clpid": "Yang-Qianhui" }, { "family_name": "Martinez-Camarillo", "given_name": "Juan Carlos", "clpid": "Martinez-Camarillo-J-C" }, { "family_name": "Cook", "given_name": "Colin A.", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C-A" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Kashani", "given_name": "Amir H.", "clpid": "Kashani-A-H" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Purpose : Diabetic retinopathy (DR) is a leading complication of diabetes. It is thought that increased rod metabolism under dark adaptation exacerbates hypoxia in diabetic retina. Nowadays most treatments for DR are invasive and need multiple clinic visits. Recently a phototherapeutic contact lens has been designed to provide illumination to retina as a means to supress dark adaptation. It may be possible to delay the progression of DR. The purpose of this study is to explore the bioactivity and safety of this device.\nMethods : Six eyes from three healthy mature white New Zealand rabbits were used. The phototherapeutic contact lens was placed on treated eye. An non-phototherapeutic contact lens was used on the fellow eye as a control. To determine bioactivity of photoreceptors, an ERG was performed. Flash response, including amplitude and implicit time on scotopic condition were analyzed at different flash intensities (100, 300, 1000, 3000, 10000, 25000 mcd.s/m^2, respectively). Animals were under a 20-minutes period of dark adaption before any ERG. Then the contact lens were swapped on the eyes and the ERG were repeated. The whole process was performed in a dark room under dim red light. Once ERG were completed, the phototherapeutic contac lens was sutured to the eye for a long\u2013term period (28 days) to verify safety. There will be a statistical analysis using Graph Pad Prism 7.0, determining the degree of correlation between the groups. Histological analysis will be performed to determine safety.\nResults : The ERG showed that both the amplitude and implicit time of b-wave in the treated eye were significantly shorter than the untreated eye under scotopic conditions (Figure 1). No significant difference in the amplitude and implicit time of a-wave was observed. A representative plot (Figure 2) shows significant depression of b-wave, both in the amplitude and implicit time (amplitude: p=0.01; implicit time: p<0.001).\nConclusions : The phototherapeutic contact lens can effectively reduce the bioactivity of the retina, without ocular side effects in an acute follow-up. Further studies should be performed for a long-term placement in both healthy and retinal ischemic animal models to determine whether this device can reduce oxygen consumption in retina and delay disease progression. Long-term histology from contact lens safety is on going and will be presented.", "issn": "0146-0404", "publisher": "Association for Research in Vision and Ophthalmology", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2018-07", "series_number": "9", "volume": "59", "issue": "9", "pages": "Art. No. 5814" }, { "id": "authors:3y8mp-w1v83", "collection": "authors", "collection_id": "3y8mp-w1v83", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181010-160848449", "type": "article", "title": "Wireless Oxygen Generator to Treat Retinal Ischemia", "author": [ { "family_name": "Martinez", "given_name": "Juan Carlos", "clpid": "Martinez-J-C" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Cook", "given_name": "Colin A.", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C-A" }, { "family_name": "Murali", "given_name": "Karthik", "clpid": "Murali-K" }, { "family_name": "Yang", "given_name": "Qianhui", "clpid": "Yang-Qianhui" }, { "family_name": "Kashani", "given_name": "Amir H.", "clpid": "Kashani-A-H" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Purpose : It is well known that retinal hypoxia plays an important role in the diabetic retinopathy (DR) pathophysiology. Current treatments of DR are focused on reducing retinal oxygen demand and controlling angiogenesis through intravitreal injections. Previous publications suggest that supplementing intravitreal oxygen might improve outcomes for retinal ischemia. A microelectronic and bio micro-electro-mechanical system oxygenator implant has been designed to transport oxygen from the sub-conjunctival space to the proximity of the inner retina. The main objective of this study is to determine safety, efficacy and therapeutic levels of vitreous cavity oxygenation needed to support the retina by electrolysis-based oxygen generation implant.\nMethods : The study was performed with local IACUC approval and in accordance with the ARVO guidelines on animal use. Three eyes of healthy pigmented rabbits (2-3kgs) were included in the study. With the animal anesthetized, the oxygenator was implanted and affixed onto the sclera. Electrolysis and intraocular measurements of partial pressure of oxygen (pO_2) were performed prior to suturing the conjunctiva back to the limbus. An oxygen probe (Oxford Optronix, London, UK) was placed intravitreal via pars plana and positioned next to the diffuser without touching adjacent structures. Baseline pO2 measurements were recorded with the device off and no electrolysis. The device was then turned on for at least 3 minutes and electrolysis was confirmed by direct visualization of bubbles. Continuous measurement of pO_2 levels next to the device were performed during electrolysis. The relationship between electrolysis and pO_2 was analyzed.\nResults : Oxygenator devices were successfully implanted. Intraocular pO_2 levels increased progressively to 79.1mmHg +5.52mmHg, 121.7mmHg +8.91mmHg and over 200mmHg after 2, 5 and 15 minutes of electrolysis, respectively (see Figure 1). Oxygen levels decreased exponentially as the probe was moved away from the device as predicted by computational models thereby minimizing oxygen toxicity to surrounding tissues. The Oxygenator implantation procedure was followed up for 7 days without presence of ocular complications.\nConclusions : Our study demonstrates that intraocular oxygen levels can be elevated following implantation and activation of the oxygenator device. Further experiments will be conducted in a long-term period.", "issn": "0146-0404", "publisher": "Association for Research in Vision and Ophthalmology", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2018-07", "series_number": "9", "volume": "59", "issue": "9", "pages": "Art. No. 5669" }, { "id": "authors:r1xy3-cfd74", "collection": "authors", "collection_id": "r1xy3-cfd74", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180518-135417850", "type": "book_section", "title": "A wireless, low-drift, implantable intraocular pressure sensor with parylene-on-oil encapsulation", "book_title": "2018 IEEE Custom Integrated Circuits Conference (CICC)", "author": [ { "family_name": "Agarwal", "given_name": "Abhinav", "clpid": "Agarwal-A" }, { "family_name": "Shapero", "given_name": "Aubrey", "clpid": "Shapero-A-M" }, { "family_name": "Rodger", "given_name": "Damien", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" } ], "abstract": "This paper presents a wireless, implantable continuous intraocular pressure (IOP) monitoring system that features a parylene-on-oil sensor encapsulation method for achieving long-term low-drift in vivo. The system is implanted in the superotemporal quadrant of the eye between the sclera and conjunctiva. It consists of a commercial pressure sensor (STMicroelectronics LPS25H) with digital readout, a 65nm CMOS chip that supports wireless power/data telemetry and the I2C serial communication interface with the pressure sensor. The chip and pressure sensor are assembled on a flexible polyimide PCB, and then the sensor is submerged in biocompatible silicone oil and coated with parylene in situ. The implant uses an on-chip integrated RF coil to receive power from near-field RF coupling at 915 MHz and transmit measurement bits via RF-backscattering to an external reader. A 2 mm \u00d7 1.2 mm chip is fabricated in TSMC 65nm CMOS process. The IOP implant achieves a pressure sensitivity of 0.17 mm Hg with a total power consumption of 9.7\u03bcW. We demonstrate pressure offset drift of less than 0.5 mmHg for more than 4 months over a temperature range of 27\u201338 \u00b0C. The implant successfully tracks induced IOP variations in a porcine eye ex vivo, validating the system functionality and surgical implantation.", "doi": "10.1109/CICC.2018.8357049", "isbn": "978-1-5386-2483-8", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2018-04", "pages": "1-4" }, { "id": "authors:k010j-zw395", "collection": "authors", "collection_id": "k010j-zw395", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180503-104340333", "type": "book_section", "title": "Phototherapeutic contact lens for diabetic retinopathy", "book_title": "2018 IEEE Micro Electro Mechanical Systems (MEMS)", "author": [ { "family_name": "Cook", "given_name": "Colin A.", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C-A" }, { "family_name": "Martinez-Camarillo", "given_name": "Juan C.", "clpid": "Martinez-Camarillo-J-C" }, { "family_name": "Yang", "given_name": "Qianhui", "clpid": "Yang-Qianhui" }, { "family_name": "Scianmarello", "given_name": "Nicholas E.", "clpid": "Scianmarello-N-E" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper reports on the first phototherapeutic \"contact lens\" to manage diabetic retinopathy by reducing retinal metabolism via suppression of rod cell dark current. The contact lens is composed of PDMS embedded with a ring of gaseous tritium light sources providing continuous illumination over the lifetime of the lens. Electroretinogram responses from rabbits demonstrate bioactivity of the lens, which is further explored in 1D simulations of retinal oxygenation. Tests in human eyes validate comfort, fit, and the Troxler neural adaptation effect. With oxygen transmissibility, DK/t, of 130 Fatt, the lens meets FDA guidelines for overnight wear and offers advantages of comfort and reliability.", "doi": "10.1109/MEMSYS.2018.8346482", "isbn": "978-1-5386-4782-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2018-01", "pages": "62-65" }, { "id": "authors:ff9f6-re677", "collection": "authors", "collection_id": "ff9f6-re677", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171108-141114924", "type": "article", "title": "Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium", "author": [ { "family_name": "Fernandes", "given_name": "Rodrigo A. Brant", "clpid": "Fernandes-R-A-B" }, { "family_name": "Stefanini", "given_name": "Francisco R.", "clpid": "Stefanini-F-R" }, { "family_name": "Falabella", "given_name": "Paulo", "clpid": "Falabella-P" }, { "family_name": "Koss", "given_name": "Michael J.", "orcid": "0000-0002-7998-9581", "clpid": "Koss-M-J" }, { "family_name": "Wells", "given_name": "Trent", "clpid": "Wells-T" }, { "family_name": "Diniz", "given_name": "Bruno", "clpid": "Diniz-B" }, { "family_name": "Ribeiro", "given_name": "Ramiro", "clpid": "Ribeiro-R" }, { "family_name": "Schor", "given_name": "Paulo", "clpid": "Schor-P" }, { "family_name": "Maia", "given_name": "Mauricio", "clpid": "Maia-M" }, { "family_name": "Penha", "given_name": "Fernando M.", "clpid": "Penha-F-M" }, { "family_name": "Hinton", "given_name": "David R.", "clpid": "Hinton-D-R" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Background:\nSubretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE).\n\nMethods:\nUltrathin Parylene-C substrates measuring 3.5 mm \u00d7 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques.\n\nResults:\nThe tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0\u20131.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure.\n\nConclusion:\nThis innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.", "doi": "10.1186/s40942-017-0095-6", "pmcid": "PMC5662097", "issn": "2056-9920", "publisher": "BioMed Central", "publication": "International Journal of Retina and Vitreous", "publication_date": "2017-10-30", "series_number": "1", "volume": "3", "issue": "1", "pages": "Art. No. 341" }, { "id": "authors:159ex-xwe75", "collection": "authors", "collection_id": "159ex-xwe75", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180322-102107647", "type": "book_section", "title": "Implantable phototherapy device to treat diabetic retinopathy", "book_title": "2017 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS)", "author": [ { "family_name": "Cook", "given_name": "Colin A.", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C-A" }, { "family_name": "Martinez-Camarillo", "given_name": "Juan C.", "clpid": "Martinez-Camarillo-J-C" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper reports on the first implantable phototherapy device to treat diabetic retinopathy by modulating rod cell metabolism through reduction of dark current. Utilizing a tritium-based radioluminescent light source capable of emitting around 505nm, the device achieves phototherapeutic activity for up to a 12-year service lifetime and <30mm^3 size. The unique scleral anchoring system facilitates simple, rapid, and robust implantation into the eye. Implantation into a rabbit model demonstrated safety over a 4-week period with no adverse effects observed.", "doi": "10.1109/TRANSDUCERS.2017.7994070", "isbn": "978-1-5386-2732-7", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2017-06", "pages": "393-396" }, { "id": "authors:vh3hs-52627", "collection": "authors", "collection_id": "vh3hs-52627", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160624-130219973", "type": "article", "title": "Biomimetic Accommodating Intraocular Lens Using a Valved Deformable Liquid Balloon", "author": [ { "family_name": "DeBoer", "given_name": "Charles M. T.", "clpid": "DeBoer-C-M-T" }, { "family_name": "Lee", "given_name": "Jonathan K.", "clpid": "Lee-Jonathan-K" }, { "family_name": "Wheelan", "given_name": "Brooks P.", "clpid": "Wheelan-B-P" }, { "family_name": "Cable", "given_name": "Craig", "clpid": "Cable-C" }, { "family_name": "Shi", "given_name": "Wendian", "clpid": "Shi-Wendian" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Objective: Presbyopia is a common age-related condition that prevents people from focusing on near objects. The etiology of presbyopia continues to be debated, but the end effect of all postulated mechanisms is the lack of deformation of the human lens. Using our understanding of the biomechanical properties of the natural human lens, we created a unique accommodating intraocular lens. Although this lens can be used for lenticular disease such as myopia and hyperoperopia, this study addresses the needs of cataract patients with presbyopia. Methods: The lens was implanted into presbyopic human cadaver eyes. Focal length of the lens was measured with simulated muscle contraction. Lens dimensions were measured using artificial tissue and a finite-element analysis (FEA) to simulate accommodation. Lens power was measured at various fill volumes. Accelerated soak testing for an equivalent of 7.4 years was performed and lens weight and optical transmittance were measured. Results: Previously presbyopic human eyes were able to accommodate between 2.0 and 7.4 diopters after lens implantation. FEA and lens measurements demonstrated a change in curvature of the anterior and posterior portions of the lens during accommodation. After accelerated aging, lens weight remained unchanged and optical transmission was 96%. Lens power increased with fill volume. Conclusion: A deformable liquid lens reversed presbyopia, can be individualized by optically adjusting for each patient, is stable for long periods of time, and is compatible with minimally invasive surgical techniques. Significance: A deformable liquid-filled lens can significantly improve accommodation over the presbyopic natural lens.", "doi": "10.1109/TBME.2015.2484379", "issn": "0018-9294", "publisher": "IEEE", "publication": "IEEE Transactions on Biomedical Engineering", "publication_date": "2016-06", "series_number": "6", "volume": "63", "issue": "6", "pages": "1129-1135" }, { "id": "authors:mwt9g-aa144", "collection": "authors", "collection_id": "mwt9g-aa144", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160307-094844172", "type": "article", "title": "Spatial Variations in Vitreous Oxygen Consumption", "author": [ { "family_name": "Murali", "given_name": "Karthik", "clpid": "Murali-K" }, { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Nazari", "given_name": "Hossein", "clpid": "Nazari-H" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Cadenas", "given_name": "Enrique", "clpid": "Cadenas-E" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Kashani", "given_name": "Amir", "clpid": "Kashani-A-H" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "We investigated the spatial variation of vitreous oxygen consumption in enucleated porcine eyes. A custom made oxygen source was fabricated that could be localized to either the mid or posterior vitreous cavity and steady state vitreous oxygen tension was measured as a function of distance from the source using a commercially available probe. The reaction rate constant of ascorbate oxidation was estimated ex vivo by measuring the change in oxygen tension over time using vitreous harvested from porcine eyes. Vitreous ascorbate from mid and posterior vitreous was measured spectrophotometrically. When the oxygen source was placed in either the mid-vitreous (N = 6) or the posterior vitreous (N = 6), we measured a statistically significant decrease in vitreous oxygen tension as a function of distance from the oxygen source when compared to control experiments without an oxygen source; (p<0.005 for mid-vitreous and p<0.018 for posterior vitreous at all distances). The mid-vitreous oxygen tension change was significantly different from the posterior vitreous oxygen tension change at 2 and 3mm distances from the respective oxygen source (p<0.001). We also found a statistically significant lower concentration of ascorbate in the mid-vitreous as compared to posterior vitreous (p = 0.02). We determined the reaction rate constant, k = 1.61 M^(-1)s^(-1) \u00b1 0.708 M^(-1)s^(-1) (SE), of the oxidation of ascorbate which was modeled following a second order rate equation. Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid-vitreous. We also show spatial variations in vitreous ascorbate concentration.", "doi": "10.1371/journal.pone.0149961", "pmcid": "PMC4773158", "issn": "1932-6203", "publisher": "Public Library of Science", "publication": "PLoS ONE", "publication_date": "2016-03-01", "series_number": "3", "volume": "11", "issue": "3", "pages": "Art. No. e0149961" }, { "id": "authors:csea5-5s512", "collection": "authors", "collection_id": "csea5-5s512", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161013-103650860", "type": "book_section", "title": "Oxygen generation by electrolysis to treat retinal ischemia", "book_title": "29th International Conference on Micro Electro Mechanical Systems (MEMS), 2016", "author": [ { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Murali", "given_name": "Karthik", "clpid": "Murali-K" }, { "family_name": "Cook", "given_name": "Colin", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C" }, { "family_name": "Han", "given_name": "Jeff", "clpid": "Han-Jeff" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper reports the first electrolysis-based oxygen generation and transportation device for the treatment of retinal ischemia; containing an isolated biocompatible electrolyte and inductive power transfer for on-demand oxygen. A finite element model of the retina along with oxygen delivery data demonstrates the feasibility of the device. The estimated therapeutic window for the device was found to be 210 minutes for the light adapted retina, and 55 minutes for the dark adapted retina.", "doi": "10.1109/MEMSYS.2016.7421645", "isbn": "978-1-5090-1973-1", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2016-01", "pages": "399-402" }, { "id": "authors:k6ttg-wep72", "collection": "authors", "collection_id": "k6ttg-wep72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141111-093651164", "type": "article", "title": "Ion Implants as Matrix-Appropriate Calibrators for Geochemical Ion Probe Analyses", "author": [ { "family_name": "Burnett", "given_name": "Donald S.", "orcid": "0000-0001-9521-8675", "clpid": "Burnett-D-S" }, { "family_name": "Jurewicz", "given_name": "Amy J. G.", "orcid": "0000-0002-3282-5782", "clpid": "Jurewicz-A-J-G" }, { "family_name": "Woolum", "given_name": "Dorothy S.", "clpid": "Woolum-D-S" }, { "family_name": "Wang", "given_name": "Jianhua", "orcid": "0000-0002-7671-2413", "clpid": "Wang-Jianhua" }, { "family_name": "Paque", "given_name": "Julie M.", "orcid": "0000-0003-0554-7876", "clpid": "Paque-J-M" }, { "family_name": "Nittler", "given_name": "Larry R.", "orcid": "0000-0002-5292-6089", "clpid": "Nittler-L-R" }, { "family_name": "McKeegan", "given_name": "Kevin D.", "clpid": "McKeegan-K-D" }, { "family_name": "Humayun", "given_name": "Munir", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Hervig", "given_name": "Richard", "clpid": "Hervig-R-L" }, { "family_name": "Heber", "given_name": "Veronika S.", "clpid": "Heber-V-S" }, { "family_name": "Guan", "given_name": "Yunbin", "orcid": "0000-0002-7636-3735", "clpid": "Guan-Yunbin" } ], "abstract": "Ion microprobe elemental and isotopic determinations can be precise but difficult to quantify. Error is introduced when the reference material and the sample to be analysed have different compositions. Mitigation of such \"matrix effects\" is possible using ion implants. If a compositionally homogeneous reference material is available which is \"matrix-appropriate,\" i.e., close in major element composition to the sample to be analysed, but having an unknown concentration of the element, E, to be determined, ion implantation can be used to introduce a known amount of an E isotope, calibrating the E concentration and producing a matrix-appropriate calibrator. Nominal implant fluences (ions cm^(\u22122)) are inaccurate by amounts up to approximately 30%. However, ion implantation gives uniform fluences over large areas, thus it is possible to \"co-implant\" an additional reference material of any bulk composition having known amounts of E, independently calibrating the implant fluence. Isotope-ratio measurement standards can be produced by implanting two different isotopes, but permil level precision requires post-implant calibration of the implant isotopic ratio. Examples discussed include: (1) standardising Li in melilite; (2) calibrating a ^(25)Mg implant fluence using NIST SRM 617 glass; and (3) using Si co-implanted with ^(25)Mg alongside NIST SRM 617 to produce a calibrated measurement of Mg in Si.", "doi": "10.1111/j.1751-908X.2014.00318.x", "issn": "1639-4488", "publisher": "Wiley", "publication": "Geostandards and Geoanalytical Research", "publication_date": "2015-09", "series_number": "3", "volume": "39", "issue": "3", "pages": "265-276" }, { "id": "authors:4b1jb-57f24", "collection": "authors", "collection_id": "4b1jb-57f24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151119-105156530", "type": "article", "title": "Retinal Vascular Oxygen Saturation in Diabetic Rats: A Study using Hyperspectral Computed Tomographic Imaging Spectroscopy", "author": [ { "family_name": "Zhang", "given_name": "Ray", "clpid": "Zhang-Ray" }, { "family_name": "You", "given_name": "Qianhaozhe", "clpid": "You-Qianhaozhe" }, { "family_name": "Martin", "given_name": "Gabriel", "clpid": "Martin-G" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Kashani", "given_name": "Amir H.", "clpid": "Kashani-A-H" } ], "abstract": "Purpose: To assess changes in retinal vascular oxygen concentration in a diabetic rat model using hyperspectral computed tomographic imaging spectroscopy (HCTIS). \n \nMethods: Nine brown Norway rats were anesthetized and dilated for retinal imaging. Six rats were injected with 65 mg/kg of Streptozotocin (STZ) to induce hyperglycemia, and 3 rats with 0.9% saline control. Blood glucose levels were measured after a 12 hour fast using Accu-Chek Aviva Plus glucometer (Roche Inc). Baseline oximetry measurements and fundus photographs were taken in both eyes of each rat. HCTIS oximetry measurements were taken every 2 weeks after STZ injection for up to 2 months. The same vessel areas were selected for analysis at each time point. Fundus photos and FA were repeated at 2 months. Comparison of retinal arterial (A_(ox)) and venous (V_(ox)) oxygen saturation levels were made at each time point using the Student T-test. \n \nResults: All experimental rats developed and maintained hyperglycemia (mean 410\u00b141 mg/dl), and all control rats remained normoglycemic (mean 124\u00b124 mg/dl) over the 2 months of the study. For control rats (n=3) mean A_(ox) was 95\u00b11%, 100\u00b14%, 97\u00b16%, 102\u00b15%, and 100\u00b17% and mean V_(ox) was 90\u00b14%, 88\u00b13%, 86\u00b13%, 87\u00b12%, and 87\u00b15% at baseline, 2, 4, 6, and 8 weeks. For experimental rats (n=6) mean A_(ox) was 91\u00b12%, 94\u00b14%, 91\u00b14%, 94\u00b13%, 94\u00b15% and mean V_(ox) was 89\u00b13%, 90\u00b14%, 88\u00b12%, 86\u00b13%, 85\u00b13% at baseline, 2, 4, 6, and 8 weeks. There were no significant differences between control and experimental A_(ox) and V_(ox) for each time point. The arteriovenous difference at each time point also showed no clear trends. V_(ox) measurements in the diabetic rats showed a decreasing V_(ox) trend over time when compared with baseline (p=0.76, 0.57, 0.17, 0.07). \n \nConclusions: There was a trend towards decreasing V_(ox) over 2 months time in experimentally induced diabetic rats but this was not statistically significant. There were no significant differences in A_(ox) and V_(ox) in rats with experimentally induced diabetes versus controls. HCTIS is a useful method for measuring retinal vascular oxygen content in the rat model.", "issn": "0146-0404", "publisher": "Lippincott, Williams & Wilkins", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2015-06", "series_number": "7", "volume": "56", "issue": "7", "pages": "Art. No. 4427" }, { "id": "authors:64kdg-89c97", "collection": "authors", "collection_id": "64kdg-89c97", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151119-105828360", "type": "article", "title": "Spatial Variation in Vitreous Oxygen Consumption", "author": [ { "family_name": "Murali", "given_name": "Karthik", "clpid": "Murali-K" }, { "family_name": "Nazari", "given_name": "Hossein", "clpid": "Nazari-H" }, { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Kashani", "given_name": "Amir H.", "clpid": "Kashani-A-H" } ], "abstract": "Purpose: The vitreous consumes oxygen via an ascorbic acid reaction with molecular oxygen. The spatiotemporal characteristics of this reaction, specifically within the eye, are not fully understood. We investigated the spatiotemporal variation of vitreous oxygen consumption in porcine cadaver eyes.\n\nMethods: Whole porcine eyes were obtained from a local slaughterhouse within 48 hours of enucleation. The native cornea and the lens were removed and replaced with a keratoprosthesis. Using a standard sclerotomy, a custom-made, semi-permeable oxygen delivery source was placed in two separate intravitreal locations (1 location per eye); the mid-vitreous (vitreous core) and posterior vitreous. A commercially made oxygen probe (Oxford Optronics) was used to measure the oxygen tension in various locations with respect to the oxygen delivery probe. For control experiments, the oxygen source was removed after the probe was positioned. After an hour in the dark, oxygen tension (pO_2) recordings were performed using a micromanipulator to retract the probe to desired distances (0, 1, 2, 3, 4mm) away from the oxygen source. A two-sided, two sample t-test was conducted to statistically compare pO_2 recordings.\n\nResults: In the presence of an oxygen source, mid-vitreous pO_2 and posterior vitreous pO_2 measurements are higher across all distances as compared to the control pO_2 measurements (N=4 for all groups). In the mid-vitreous experiments, there was a statistically significant difference between the oxygen source and control; (p<0.005) at all distances (0, 1, 2, 3, 4mm). In the posterior vitreous experiments, there was a statistically significant difference between oxygen source and control at all distances as well; 0mm (p<0.01), 1mm (p=0.01), 2mm (p<0.01), and 3mm (p=0.018) distances. Oxygen tension recordings are higher in the mid-vitreous compared to the posterior vitreous at all distances. The mid-vitreous oxygen tension is significantly different from the posterior vitreous oxygen tension at 2 and 3mm (p<0.001). \n \nConclusions: Our data demonstrates that vitreous oxygen consumption is higher in the posterior vitreous compared to the mid vitreous. This may be important in understanding the role of vitreous cortex and vitreous core in oxygen homeostasis. These findings also have important implications in the modeling of oxygen consumption in the vitreous and eye.", "issn": "0146-0404", "publisher": "Lippincott, Williams & Wilkins", "publication": "Investigative Ophthalmology and Visual Science", "publication_date": "2015-06", "series_number": "7", "volume": "56", "issue": "7", "pages": "Art. No. 4416" }, { "id": "authors:98fqx-r9m10", "collection": "authors", "collection_id": "98fqx-r9m10", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151113-113545991", "type": "article", "title": "Imaging Novel Ruthenium bipyridine-based Nanophotoswitches in Retina", "author": [ { "family_name": "Yue", "given_name": "Lan", "clpid": "Yue-Lan" }, { "family_name": "Walston", "given_name": "Sean", "clpid": "Walston-S" }, { "family_name": "Lin", "given_name": "Mingyi S.", "clpid": "Lin-Mingyi-S" }, { "family_name": "Pribisko", "given_name": "Melanie", "clpid": "Pribisko-M-A" }, { "family_name": "Dougherty", "given_name": "Dennis", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Grubbs", "given_name": "R.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Gray", "given_name": "Harry", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Chow", "given_name": "Robert", "clpid": "Chow-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "Nanophotoswitches (NPSs) offer a new tool for optical\nstimulation of neuronal activity, in vitro and also potentially in vivo. Our group previously reported a ruthenium bipyridine (Rubpy)-based NPS that inserts into the plasma membrane and upon visible illumination generates an electrical dipole, triggering action potentials in adrenal chromaffin cells. We have recently demonstrated\nthat after intravitreal injection of this NPS into the eyes of blind rats, illumination of the eye elicited electrical activity in the contralateral superior colliculus. To better understand the site of action of the NPS in retina, we examined the distribution of the molecules in different\nretinal layers after intravitreal injection.\n\nMethods: Rubpy molecules can be visualized by their luminescence (610 nm) upon visible wavelength illumination (460 nm). To resolve the luminescence from different retinal layers, a rapid-scan twophoton imaging system (LaVison) was used (Ti:Sapphire laser tuned to 900 nm). Intravitreal injection (1 mM, 4 \u03bcL Rubpy-based NPSs\nin BSS), followed by eye removal and retina isolation 2-5 hrs after, was performed on young RCS rats. Luminescence images of the wholemount retina were captured by an EM-CCD camera (Andor). \n\nResults: At 2 hrs after intravitreal injection and with continuous superfusion of Ames medium, luminescence was confined near the injection site. Luminescence was observed localized to surface membranes of axons and somata of retinal ganglion cells (RGC), demonstrating the impermeability of the cell membrane to the NPS molecules. The outer retina did not show significant luminescence.\nAfter 3 additional hours, luminescence was more diffused within the RGC layer and still did not extend to the outer retina. \n\nConclusions: This study shows marked staining of RGC layer by intravitreally injected Rubpy-based NPS molecules, consistent with the hypothesis that the photoactivated NPS molecules induce electrical activity in the superior colliculus by acting on the RGCs that deliver electrical signals to the visual pathway outside the eyes. Distinct from other nano-scale optical cellular modulating approaches using optogenetics or azobenzene-based photoswitches, the NPS approach obviates the need for gene manipulation or toxic UV illumination, highlighting its potential in generating high-acuity prosthetic vision in patients blinded by retinal degenerative diseases.", "issn": "0146-0404", "publisher": "ARVO", "publication": "Investigative ophthalmology & visual science", "publication_date": "2015-06", "series_number": "7", "volume": "56", "issue": "7", "pages": "1676-1676" }, { "id": "authors:4xdw3-vgx22", "collection": "authors", "collection_id": "4xdw3-vgx22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150605-135556686", "type": "book_section", "title": "Simulation and measurement of transcranial near infrared light penetration", "book_title": "Optical Interactions with Tissue and Cells XXVI", "author": [ { "family_name": "Yue", "given_name": "Lan", "clpid": "Yue-Lan" }, { "family_name": "Monge", "given_name": "Manuel", "orcid": "0000-0001-9799-0693", "clpid": "Monge-Manuel" }, { "family_name": "Ozgur", "given_name": "Mehmet H.", "clpid": "Ozgur-M-H" }, { "family_name": "Murphy", "given_name": "Kevin", "clpid": "Murphy-K" }, { "family_name": "Louie", "given_name": "Stan", "clpid": "Louie-S" }, { "family_name": "Miller", "given_name": "Carol A.", "clpid": "Miller-C-A" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "contributor": [ { "family_name": "Jansen", "given_name": "E. Duco" } ], "abstract": "We are studying the transmission of LED array-emitted near-infrared (NIR) light through human tissues. Herein, we simulated and measured transcranial NIR penetration in highly scattering human head tissues. Using finite element analysis, we simulated photon diffusion in a multilayered 3D human head model that consists of scalp, skull, cerebral spinal fluid, gray matter and white matter. The optical properties of each layer, namely scattering and absorption coefficient, correspond to the 850 nm NIR light. The geometry of the model is minimally modified from the IEEE standard and the multiple LED emitters in an array were evenly distributed on the scalp. Our results show that photon distribution produced by the array exhibits little variation at similar brain depth, suggesting that due to strong scattering effects of the tissues, discrete spatial arrangements of LED emitters in an array has the potential to create a quasi-radially symmetrical illumination field. Measurements on cadaveric human head tissues excised from occipital, parietal, frontal and temporal regions show that illumination with an 850 nm LED emitter rendered a photon flux that closely follows simulation results. In addition, prolonged illumination of LED emitted NIR showed minimal thermal effects on the brain.", "doi": "10.1117/12.2077019", "isbn": "978-1-62841-411-0", "publisher": "SPIE", "place_of_publication": "Bellingham, Washington", "publication_date": "2015-03-05", "pages": "Art. No. 93210S" }, { "id": "authors:792jg-d9b91", "collection": "authors", "collection_id": "792jg-d9b91", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160317-142016193", "type": "book_section", "title": "MEMS oxygen transporter to treat retinal ischemia", "book_title": "28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2015)", "author": [ { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Murali", "given_name": "Karthik", "clpid": "Murali-K" }, { "family_name": "Scianmarello", "given_name": "Nicholas", "clpid": "Scianmarello-N" }, { "family_name": "Park", "given_name": "Jungwook", "clpid": "Park-Jungwook" }, { "family_name": "Chang", "given_name": "Jay Han-Chieh", "clpid": "Chang-Jay-Han-Chieh" }, { "family_name": "Liu", "given_name": "Yang", "orcid": "0000-0002-8155-9134", "clpid": "Liu-Yang" }, { "family_name": "Chang", "given_name": "Kai-Tang", "clpid": "Chang-Kai-Tang" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "For the first time, a paradigm shift in the treatment of retinal ischemia is proposed: providing localized supplemental oxygen to the ischemic tissue via an implanted MEMS device. A passive MEMS oxygen transporter is designed, built and tested in both artificial eye models and porcine cadaver eyes to confirm various hypotheses. The finite element modeling results predict that the proposed approach can treat complete retinal ischemia.", "doi": "10.1109/MEMSYS.2015.7050909", "isbn": "978-1-4799-7955-4", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2015-01", "pages": "154-157" }, { "id": "authors:k5kgc-jwy54", "collection": "authors", "collection_id": "k5kgc-jwy54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140225-114331568", "type": "article", "title": "A Fully Intraocular High-Density Self-Calibrating Epiretinal Prosthesis", "author": [ { "family_name": "Monge", "given_name": "Manuel", "orcid": "0000-0001-9799-0693", "clpid": "Monge-Manuel" }, { "family_name": "Raj", "given_name": "Mayank", "clpid": "Raj-M" }, { "family_name": "Nazari", "given_name": "Meisam Honarvar", "clpid": "Nazari-M-H" }, { "family_name": "Chang", "given_name": "Han-Chieh", "clpid": "Chang-Han-Chieh" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" } ], "abstract": "This paper presents a fully intraocular self-calibrating epiretinal prosthesis with 512 independent channels in 65 nm CMOS. A novel digital calibration technique matches the biphasic currents of each channel independently while the calibration circuitry is shared among every 4 channels. Dual-band telemetry for power and data with on-chip rectifier and clock recovery reduces the number of off-chip components. The rectifier utilizes unidirectional switches to prevent reverse conduction loss in the power transistors and achieves an efficiency > 80%. The data telemetry implements a phase-shift keying (PSK) modulation scheme and supports data rates up to 20 Mb/s. The system occupies an area of 4.5 \u00d73.1 mm^2. It features a pixel size of 0.0169 mm^2 and arbitrary waveform generation per channel. In vitro measurements performed on a Pt/Ir concentric bipolar electrode in phosphate buffered saline (PBS) are presented. A statistical measurement over 40 channels from 5 different chips shows a current mismatch with \u03bc = 1.12 \u03bcA and \u03c3 = 0.53 \u03bcA. The chip is integrated with flexible MEMS origami coils and parylene substrate to provide a fully intraocular implant.", "doi": "10.1109/TBCAS.2014.2298334", "issn": "1932-4545", "publisher": "IEEE", "publication": "IEEE Transactions on Biomedical Circuits and Systems", "publication_date": "2013-12", "series_number": "6", "volume": "7", "issue": "6", "pages": "747-760" }, { "id": "authors:emdt5-kcg02", "collection": "authors", "collection_id": "emdt5-kcg02", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140520-140334969", "type": "book_section", "title": "Parylene origami structure for intraocular implantation", "book_title": "2013 Transducers & Eurosensors XXVII", "author": [ { "family_name": "Liu", "given_name": "Yang", "orcid": "0000-0002-8155-9134", "clpid": "Liu-Yang" }, { "family_name": "Park", "given_name": "Jungwook", "clpid": "Park-Jungwook" }, { "family_name": "Lang", "given_name": "Robert J.", "clpid": "Lang-R-J" }, { "family_name": "Emami-Neyestanak", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Pellegrino", "given_name": "Sergio", "orcid": "0000-0001-9373-3278", "clpid": "Pellegrino-S" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the use of origami technique to construct a 3D spherical structure from a 2D parylene-C (PA-C) film with designed folding crease patterns. This origami technique is developed or intended for intraocular epiretinal implant application, which requires a \"curved\" electrode array to match the curvature of the macula. The folding method and process are described here using silicone oil as a temporary glue to hold the folded structures through meniscus force. The temporary origami is then thermally set into permanent 3D shapes at 100 \u00b0C for 30 minutes in vacuum utilizing parylene-C's viscoelastic properties. The reported origami technique enables the possibility of first making an extended device in 2D format and, after a possible minimal surgical cut and insertion, then folding it into a 3D device inside the eye for necessary geometric matching with host tissues.", "doi": "10.1109/Transducers.2013.6627077", "isbn": "9781467359818", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2013-06", "pages": "1549-1552" }, { "id": "authors:ay50a-hpk89", "collection": "authors", "collection_id": "ay50a-hpk89", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170125-164509091", "type": "book_section", "title": "A fully intraocular 0.0169 mm^2/pixel 512-channel self-calibrating epiretinal prosthesis in 65nm CMOS", "book_title": "2013 IEEE International Solid-State Circuits Conference Digest of Technical Papers", "author": [ { "family_name": "Monge", "given_name": "Manuel", "orcid": "0000-0001-9799-0693", "clpid": "Monge-Manuel" }, { "family_name": "Raj", "given_name": "Mayank", "clpid": "Raj-M" }, { "family_name": "Honarvar-Nazari", "given_name": "Meisam", "clpid": "Honarvar-Nazari-M" }, { "family_name": "Chang", "given_name": "Han-Chieh", "clpid": "Chang-Han-Chieh" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Weiland", "given_name": "James", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Emami-Neyestanak", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" } ], "abstract": "Since their conception and success in human trials, the flexibility and spatial resolution of retinal prostheses have been of major interest. Clinical studies have revealed that hundreds of channels are needed to restore functional visual perception, and more sophisticated waveforms present advantages over biphasic pulses. Initial designs targeted stimulation current levels up to 1mA to ensure functionality. For such designs, an output compliance of >10V was required, and HV technologies were used at the expense of area and power consumption. Human clinical trials have recently shown that implanted electrodes present a stimulus threshold as low as 50\u03bcA. In addition, advances in implant technology promise close placement of electrode array and retinal tissue, which can further decrease the required current. Thus, highly scaled LV technologies can provide alternative means to reduce area and power, and to support hundreds of flexible independent channels for fully intraocular implants. In this paper, a self-calibrating 512-channel epiretinal prosthesis in 65nm CMOS is presented. It features dual-band telemetry for power and data, clock recovery, a 2-step calibration technique to match biphasic stimulation currents, and an independent arbitrary output waveform per channel. The implant integrates coils (power and data), IC, external capacitors and electrode array using a biocompatible parylene substrate, providing a fully intraocular solution.", "doi": "10.1109/ISSCC.2013.6487742", "isbn": "978-1-4673-4516-3", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2013-02", "pages": "296-297" }, { "id": "authors:ymwfe-01248", "collection": "authors", "collection_id": "ymwfe-01248", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130729-090047591", "type": "book_section", "title": "Packaging study for a 512-channel intraocular epiretinal implant", "book_title": "IEEE 26th International Conference on Micro Electro Mechanical Systems (MEMS)", "author": [ { "family_name": "Chang", "given_name": "Jay Han-Chieh", "clpid": "Chang-Jay-Han-Chieh" }, { "family_name": "Liu", "given_name": "Yang", "orcid": "0000-0002-8155-9134", "clpid": "Liu-Yang" }, { "family_name": "Kang", "given_name": "Dongyang", "clpid": "Kang-Dongyang" }, { "family_name": "Monge", "given_name": "Manuel", "orcid": "0000-0001-9799-0693", "clpid": "Monge-Manuel" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Yu" }, { "family_name": "Yu", "given_name": "Chia-Chen", "clpid": "Yu-Chia-Chen" }, { "family_name": "Emami-Neyestanak", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Weiland", "given_name": "James", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Much effort has been put into developing multi-channel retinal prosthetic devices. Currently, even the most advanced prostheses do not have enough channels to provide vision to a desirable level. In this paper, we present a system design and a packaging scheme for a 512-channel intraocular epiretinal implant. Both a wireless power coil (with high transfer efficiency) and a data coil are included for this intraocular system. Simulation of the interference between coils is investigated and the results show that the two coils can be put in a co-planar fashion using two notch filters to minimize interference. The complete package is demonstrated with a mechanical model with a parylene-C flexible circuit board, i.e., parylene flex, to show the placement of the IC chips, discrete components, and coils. It also shows the final folded device after surgical insertion into an eye to save space. The feasibility of the proposed structure has been successfully tested in vivo. Experimentally, the maximum allowable pulling force is measured by a dynamic mechanical analysis (DMA) machine to be 8N, which provides a large safety margin for surgery.", "doi": "10.1109/MEMSYS.2013.6474428", "isbn": "978-1-4673-5654-1", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2013-01", "pages": "1045-1048" }, { "id": "authors:0sr11-twf73", "collection": "authors", "collection_id": "0sr11-twf73", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120828-133907808", "type": "article", "title": "Feeling the Pressure: A Parylene-Based Intraocular Pressure Sensor", "author": [ { "family_name": "Lin", "given_name": "Chun-Hui J.", "clpid": "Lin-C-H-J" }, { "family_name": "Zhao", "given_name": "Yu", "clpid": "Zhao-Y" }, { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-P-J" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Intraocular pressure (IOP) is important for the prevention and treatment of certain human eye diseases. For example, glaucoma is the second leading cause of blindness in the world according to the World Health Organization [1]. The majority of glaucoma patients have an IOP > 20 mmHg (compared with a normal IOP of 10 mmHg), which could damage patients optic nerves in the backside of the eye and cause irreversible blindness. Currently, there is no cure for glaucoma, but with early diagnosis and proper treatment, the visual loss can be slowed or eliminated. Due to the lack of other symptoms or pain, and the eye's ability to compensate for loss of peripheral vision, many glaucoma patients are unaware of the disease's development until it is severe. In fact, only half of the patients in the United States are aware of having glaucoma. Therefore, early diagnosis and treatment are important to prevent blindness. Thus, a device to diagnose early-stage glaucoma is in demand.", "doi": "10.1109/MNANO.2012.2203876", "issn": "1932-4510", "publisher": "IEEE", "publication": "IEEE Nanotechnology Magazine", "publication_date": "2012-09", "series_number": "3", "volume": "6", "issue": "3", "pages": "8-16" }, { "id": "authors:c0qnq-5s905", "collection": "authors", "collection_id": "c0qnq-5s905", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120730-114002078", "type": "article", "title": "Mesh-supported submicron parylene-C membranes for culturing retinal pigment epithelial cells", "author": [ { "family_name": "Lu", "given_name": "Bo", "clpid": "Lu-B" }, { "family_name": "Zhu", "given_name": "Danhong", "clpid": "Zhu-D" }, { "family_name": "Hinton", "given_name": "David", "clpid": "Hinton-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "In this work, a mesh-supported submicron parylene-\nC membrane (MSPM) is proposed as an artificial Bruch's\nmembrane for the therapy of age-related macular degeneration\n(AMD). Any artificial Bruch's membrane must first satisfy two important requirements. First, it should be as permeable as healthy human Bruch's membrane to support nutrients transportation. Secondly, it should be able to support the adherence and proliferation of retinal pigment epithelial (RPE) cells with in vivo-like morphologies and functions. Although parylene-C is widely used as a barrier layer in many biomedical applications, it is found that parylene-C membranes with submicron thickness are semipermeable to macromolecules.We first measure the permeability of submicron parylene-C and find that\n0.15\u20130.30 \u03bcm parylene-C has similar permeability to healthy\nhuman Bruch's membranes. Blind-well perfusion cell viability\nexperiments further demonstrate that nutrients and macromolecules\ncan diffuse across 0.30 \u03bcm parylene-C to nourish the\ncells. A mesh-supported submicron parylene-C membrane\n(MSPM) structure is design to enhance the mechanical strength of the substrate. In vitro cells culture on the MSPM (with 0.30 \u03bcm ultrathin parylene-C) shows that H9-RPE cells are able to adhere, proliferate, form epithelial monolayer with tight intracellular junctions, and become well-polarized with microvilli, which exhibit similar characteristics to RPE cells in vivo. These studies have demonstrated the potential of the MSPM as an artificial Bruch's membrane for RPE cell transplantation.", "doi": "10.1007/s10544-012-9645-8", "issn": "1387-2176", "publisher": "Springer", "publication": "Biomedical Microdevices", "publication_date": "2012-08", "series_number": "4", "volume": "14", "issue": "4", "pages": "659-667" }, { "id": "authors:xejs7-q5w71", "collection": "authors", "collection_id": "xejs7-q5w71", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20121002-155323510", "type": "article", "title": "Evidence for Unfractionated Magnesium Isotopes in Genesis SOS Wafers", "author": [ { "family_name": "Humayun", "given_name": "M.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Jurewicz", "given_name": "A. J. G.", "orcid": "0000-0002-3282-5782", "clpid": "Jurewicz-A-J-G" }, { "family_name": "Olinger", "given_name": "C.", "clpid": "Olinger-C" }, { "family_name": "Burnett", "given_name": "D. S.", "orcid": "0000-0001-9521-8675", "clpid": "Burnett-D-S" } ], "abstract": "Oxygen isotopes measured by MegaSIMS on\nGenesis Concentrator samples indicate a solar wind (SW) oxygen isotope composition that is related to the ^(16)O-enriched CAI composition by a large mass dependent fractionation [I]. Isotope fractionation during acceleration of the solar wind is expected to create\nsuch a large mass fractionation, but a direct test of the presence of mass fractionation in the solar wind has not been possible with sufficient precision. Unlike O and Ne, Mg isotopes are sufficiently uniform in chondrites, terrestrial samples, and other meteoritic and planetary materials from the inner solar system [2], and so offer the best opportunity for a precise (\u00b11\u2030) test of the Coulomb Drag mechanism for solar wind isotope fractionation.", "doi": "10.1111/j.1945-5100.2012.01401_2.x", "issn": "1086-9379", "publisher": "Meteoritical Society", "publication": "Meteoritics and Planetary Science", "publication_date": "2012-07", "series_number": "S1", "volume": "47", "issue": "S1", "pages": "A202-A202" }, { "id": "authors:4bdbx-gxt80", "collection": "authors", "collection_id": "4bdbx-gxt80", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130201-100453140", "type": "book_section", "title": "A 3D parylene scaffold cage for culturing retinal pigment epithelial cells", "book_title": "2012 IEEE 25th International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Lu", "given_name": "Bo", "clpid": "Lu-B" }, { "family_name": "Zhu", "given_name": "Danhong", "clpid": "Zhu-D" }, { "family_name": "Hinton", "given_name": "David", "clpid": "Hinton-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This work reports a 3D parylene scaffold cage for culturing stem-cell-differentiated retinal pigment epithelial (RPE) cells for the therapy of age-related macular degeneration, which is caused by degenerated permeability of the Bruch's membrane first and then the loss of RPE cells. This reported cage can support sufficient nutrient permeation to nourish the RPE cells inside with in vivo like morphology. Compared to previous single layer scaffold substrates, this cage can effectively prevent the undesirable cell migration away from the scaffold.", "doi": "10.1109/MEMSYS.2012.6170292", "isbn": "978-1-4673-0325-5", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2012-01", "pages": "741-744" }, { "id": "authors:bz9dh-qsf10", "collection": "authors", "collection_id": "bz9dh-qsf10", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170213-164318264", "type": "book_section", "title": "Semipermeable parylene membrane as an artificial Bruch's membrane", "book_title": "16th International Solid-State Sensors, Actuators and Microsystems Conference", "author": [ { "family_name": "Lu", "given_name": "Bo", "clpid": "Lu-Bo" }, { "family_name": "Liu", "given_name": "Zhao", "orcid": "0000-0003-0370-2406", "clpid": "Liu-Zhao" }, { "family_name": "Liu", "given_name": "Laura", "clpid": "Liu-Laura" }, { "family_name": "Zhu", "given_name": "Danhong", "clpid": "Zhu-Danhong" }, { "family_name": "Hinton", "given_name": "David", "clpid": "Hinton-D" }, { "family_name": "Thomas", "given_name": "Biju", "clpid": "Thomas-B-B" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper investigates the feasibility of a mesh-supported submicron-thick semipermeable parylene-C membrane as an artificial Bruch's membrane for the treatment of age-related macular degeneration (AMD). First, the permeabilities of parylene-C membranes with different thickness were measured and the results showed that as-deposited 0.30\u03bcm-thick parylene-C, which has a similar permeability to biological Bruch's membrane, is a good candidate to replace the diseased Bruch's membrane. This was further validated by perfusion cell culture experiments, in which nutrients were supplied to the cultured cells only by permeation through the submicron membrane. It was also found that retinal pigment epithelial (RPE) cells could grow and well-polarize with normal morphology on the membrane Finally, the implantation of the submicron-thick membrane (with in vitro cultured RPE cells) into rat's retina was successfully done with the help of a parylene-C/SU-8 microsurgical tool, and the following histological study of the retina showed that the reported thin parylene-C membrane could be a promissing RPE substrate candidate for further study.", "doi": "10.1109/TRANSDUCERS.2011.5969376", "isbn": "978-1-4577-0156-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2011-06", "pages": "950-953" }, { "id": "authors:p49d0-rnz71", "collection": "authors", "collection_id": "p49d0-rnz71", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110506-112304271", "type": "article", "title": "Parylene-based integrated wireless single-channel neurostimulator", "author": [ { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Pinto", "given_name": "Anderson", "clpid": "Pinto-A" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-Ellis-M" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the design, fabrication, and functional testing of a fully implantable, flexible, Parylene-enable neurostimulator that features single-channel wireless stimulation capability [1]. This system comprises a fold-and-bond microelectromechanical systems (MEMS) coil for wireless power and data transmission, a BION 1-3 CMOS stimulator chip, discrete capacitors, as well as a carrier substrate with two platinum stimulating electrodes and interconnections for system assembly. The physical geometries of the devices are designed for use in retinal implantation with the specifications determined from the implantation results in canine eyes. The coil and carrier substrate are separately fabricated using a Parylene\u2013metal skin technology. The unique properties of Parylene C allow these MEMS devices to be flexible and biocompatible, facilitating surgical procedure. The system assembly is achieved by interconnecting individual components together on the carrier substrate with a biocompatible silver epoxy. A 10 \u03bcm layer of Parylene C is selectively deposited on the integrated system to protect it from corrosive eye environment. The system functionality is verified using a telemetry link setup, and single-phase pulses with amplitudes ranging from 7 to 8.5 V are detected.", "doi": "10.1016/j.sna.2010.03.003", "issn": "0924-4247", "publisher": "Elsevier", "publication": "Sensors and Actuators A", "publication_date": "2011-04", "series_number": "2", "volume": "166", "issue": "2", "pages": "193-200" }, { "id": "authors:jjqjr-sqe25", "collection": "authors", "collection_id": "jjqjr-sqe25", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101117-094431583", "type": "article", "title": "Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-P-J" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Varma", "given_name": "Rohit", "clpid": "Varma-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents an implant-based wireless pressure\nsensing paradigm for long-range continuous intraocular\npressure (IOP) monitoring of glaucoma patients. An implantable\nparylene-based pressure sensor has been developed, featuring an\nelectrical LC-tank resonant circuit for passive wireless sensing\nwithout power consumption on the implanted site. The sensor\nis microfabricated with the use of parylene C (poly-chlorop-\nxylylene) to create a flexible coil substrate that can be folded\nfor smaller physical form factor so as to achieve minimally invasive\nimplantation, while stretched back without damage for\nenhanced inductive sensor\u2013reader coil coupling so as to achieve\nstrong sensing signal. A data-processed external readout method\nhas also been developed to support pressure measurements. By\nincorporating the LC sensor and the readout method, wireless\npressure sensing with 1-mmHg resolution in longer than 2-cm distance\nis successfully demonstrated. Other than extensive on-bench\ncharacterization, device testing through six-month chronic in vivo\nand acute ex vivo animal studies has verified the feasibility and\nefficacy of the sensor implant in the surgical aspect, including\nrobust fixation and long-term biocompatibility in the intraocular\nenvironment. With meeting specifications of practical wireless\npressure sensing and further reader development, this sensing\nmethodology is promising for continuous, convenient, direct, and\nfaithful IOP monitoring.", "doi": "10.1109/JMEMS.2010.2049825", "issn": "1057-7157", "publisher": "IEEE", "publication": "Journal of Microelectromechanical Systems", "publication_date": "2010-08", "series_number": "4", "volume": "19", "issue": "4", "pages": "721-734" }, { "id": "authors:25brc-8p520", "collection": "authors", "collection_id": "25brc-8p520", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101118-134541510", "type": "article", "title": "Wafer-Level Parylene Packaging With Integrated RF Electronics for Wireless Retinal Prostheses", "author": [ { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-Ellis-M" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents an embedded chip integration\ntechnology that incorporates silicon housings and flexible\nParylene-based microelectromechanical systems (MEMS) devices.\nAccelerated-lifetime soak testing is performed in saline at elevated\ntemperatures to study the packaging performance of Parylene C\nthin films. Experimental results show that the silicon chip under\ntest is well protected by Parylene, and the lifetime of Parylenecoated\nmetal at body temperature (37\u00b0C) is more than 60 years,\nindicating that Parylene C is an excellent structural and packaging\nmaterial for biomedical applications. To demonstrate the proposed\npackaging technology, a flexible MEMS radio-frequency (RF) coil\nhas been integrated with an RF identification (RFID) circuit die.\nThe coil has an inductance of 16 \u03bcH with two layers of metal\ncompletely encapsulated in Parylene C, which is microfabricated\nusing a Parylene\u2013metal\u2013Parylene thin-film technology. The chip\nis a commercially available read-only RFID chip with a typical\noperating frequency of 125 kHz. The functionality of the embedded\nchip has been tested using an RFID reader module in both air\nand saline, demonstrating successful power and data transmission\nthrough the MEMS coil.", "doi": "10.1109/JMEMS.2010.2049985", "issn": "1057-7157", "publisher": "IEEE", "publication": "Journal of Microelectromechanical Systems", "publication_date": "2010-08", "series_number": "4", "volume": "19", "issue": "4", "pages": "735-742" }, { "id": "authors:mh96f-k1052", "collection": "authors", "collection_id": "mh96f-k1052", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170314-161916848", "type": "book_section", "title": "Ex Vivo implantation study of minimally invasive glaucoma drainage device", "book_title": "IEEE 5th International Conference on Nano/Micro Engineered and Molecular Systems", "author": [ { "family_name": "Lin", "given_name": "Jeffrey Chun-Hui", "clpid": "Lin-Jeffrey-Chun-Hui" }, { "family_name": "Yu", "given_name": "Feiqiao", "clpid": "Yu-Feiqiao" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Varma", "given_name": "Rohit", "clpid": "Varma-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "We present in this paper the first ex vivo implantation results of our minimally invasive glaucoma drainage device (GDD.) The GDD is designed to treat glaucoma patients by draining out their extraneous aqueous humor out of the anterior chamber utilizing a MEMS micro-fluidic normally closed (NC) check valve. The NC check valve is encapsulated in protective tubing made from parylene C, which has been proved to be biocompatible in implantation. A new packaging and a bench-top testing procedure is established to characterize the integrated GDD prior to its implantation into enucleated porcine eyes. Pre-implanted characterization curve demonstrates a cracking pressure of 10\u201320 mmHg of the NC check valve, which agrees with our theoretical design. Ex vivo implantation results show that cracking pressure is measured as 24 mmHg by unloading the eye pressure. The little offset of the cracking pressure comes from the differences between the in vitro and ex vivo testing environments. The hysteresis behavior of the NC check valve is also examined during implantation and is presented here.", "doi": "10.1109/NEMS.2010.5592223", "isbn": "978-1-4244-6545-3", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2010-01", "pages": "321-324" }, { "id": "authors:fd1gb-nen47", "collection": "authors", "collection_id": "fd1gb-nen47", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170327-174424552", "type": "book_section", "title": "Implantable Flexible-Coiled Wireless Intraocular Pressure Sensor", "book_title": "IEEE 22nd International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Varma", "given_name": "Rohit", "clpid": "Varma-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This work presents an implantable wireless passive pressure sensor for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. The sensor is microfabricated with use of parylene C (poly-chloro-p-xylylene) to create a flexible coil substrate that can be folded during implantation for suture-less minimally invasive surgery, while stretched back without damage for enhanced inductive sensor-reader coil coupling and the corresponding sensing signal. Extensive device characterizations including on-bench testing and in vivo and ex vivo animal studies verify the device feasibility in both engineering (1 mmHg pressure sensing accuracy and 2 cm sensing distance) and surgical (robust fixation to the iris and long-term biocompatibility in the intraocular environment) aspects, all meeting specifications for future practical implementation of such IOP sensing technology.", "doi": "10.1109/MEMSYS.2009.4805364", "isbn": "978-1-4244-2977-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2009-01", "pages": "244-247" }, { "id": "authors:vs1at-tkv29", "collection": "authors", "collection_id": "vs1at-tkv29", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170323-135102342", "type": "book_section", "title": "Minimally Invasive Parylene Dual-Valved Flow Drainage Shunt for Glaucoma Implant", "book_title": "IEEE 22nd International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Lin", "given_name": "Jeffrey Chun-Hui", "clpid": "Lin-Jeffrey-Chun-Hui" }, { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Yu", "given_name": "Brian", "clpid": "Yu-Brian" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "A parylene-enabled microvalved shunt implant for glaucoma drainage is presented in this paper. Enabled by the dual-checkvalve operation, this device can physically drain the extra intraocular fluid and regulate the intraocular pressure (IOP) within the normal range (15-20 mmHg). Improved surgical features, in addition to the functional/microfluidic components, such as parylene-tube carrier and anchors, are also incorporated in such device to realize minimally invasive suture-less implantation, suitable for practical in vivo use. With the optimized micromachining and post-fabrication process procedures, the developed implant is the first checkvalved glaucoma drainage device (GDD), which is passive, consumes no additional power, and functions without any circuit involved to pursue its medical application.", "doi": "10.1109/MEMSYS.2009.4805352", "isbn": "978-1-4244-2977-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2009-01", "pages": "196-199" }, { "id": "authors:swnwa-h7e83", "collection": "authors", "collection_id": "swnwa-h7e83", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190322-120334812", "type": "book_section", "title": "Systems design of a high resolution retinal prosthesis", "book_title": "2008 IEEE International Electron Devices Meeting", "author": [ { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Fink", "given_name": "Wolfgang", "clpid": "Fink-W" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Liu", "given_name": "Wentai", "clpid": "Liu-Wentai" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Sivaprakasam", "given_name": "Mohanasankar", "clpid": "Sivaprakasam-M" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Tarbell", "given_name": "Mark A.", "clpid": "Tarbell-M-A" } ], "abstract": "Simulations of artificial vision suggest that 1000 electrodes may be required to restore vision to individuals with diseases of the outer retina. In order to achieve such an implant, new technology is needed, since the state-of-the-art implantable neural stimulator has at most 22 contacts with neural tissue. Considerable progress has been made towards that goal with the development of image processing, microelectronics, and polymer based MEMS. An image processing system has been realized that is capable of real-time implementation of image decimation and filtering (for example, edge detection). Application specific integrated circuits (ASICs) have been designed and tested to demonstrate closed loop power control and efficient microstimulation. A novel packaging process has been developed that is capable of simultaneously forming communication coils, interconnects, and stimulating electrodes.", "doi": "10.1109/iedm.2008.4796682", "isbn": "9781424423774", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2008-12", "pages": "1-4" }, { "id": "authors:qdr0w-7sj63", "collection": "authors", "collection_id": "qdr0w-7sj63", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CHEjmems08b", "type": "article", "title": "Floating-Disk Parylene Microvalves for Self-Pressure-Regulating Flow Controls", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the first parylene-based floating-disk microvalve with self-pressure-regulating characteristics for various microfluidic applications. By incorporating a free-floating disk diaphragm with no anchoring/tethering structures to constrain its movement, the microvalve realizes configurable pressure-based flow-shunting functions in a stand-alone fashion. Its passive operation eliminates the need for power sources or the external actuation of the device. A multilayer polymer surface-micromachining technology is utilized for device fabrication by exploiting parylene C (poly-chloro-p-xylylene) as the biocompatible structural material for high mechanical compliance as compared with other conventional thin-film materials. Experimental results successfully demonstrate that the in-channel microvalves control water flows in the following two different shunt designs: 1) a nearly ideal regular check valve with zero forward-cracking pressure, zero reverse leakage, and 1.25 x 10^13 - 2.09 x 10^13 N\u00b7s/m^5 (0.03\u20130.05 psi\u00b7min/\u03bcL, 1.55\u20132.59 mmHg\u00b7min/\u03bcL) of fluidic resistance; and 2) a pressure\u2013bandpass check valve with 0\u2013100 mmHg and 0\u201310 \u03bcL/min of pressure and flow rate regulation ranges, respectively, as well as 4.88 x 10^13 N\u00b7s/m^5 (0.12 psi\u00b7min/\u03bcL, 6.08 mmHg\u00b7min/\u03bcL) of fluidic resistance in the forward conductive region. Such a biocompatible and implantable microvalve has the great potential of being integrated in microfluidic systems to facilitate effective microflow control for lab-on-a-chip and biomedical applications.", "doi": "10.1109/JMEMS.2008.2004947", "issn": "1057-7157", "publisher": "IEEE", "publication": "Journal of Microelectromechanical Systems", "publication_date": "2008-12", "series_number": "6", "volume": "17", "issue": "6", "pages": "1352-1361" }, { "id": "authors:cqrqx-wp528", "collection": "authors", "collection_id": "cqrqx-wp528", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CHEjmems08a", "type": "article", "title": "Microfabricated Implantable Parylene-Based Wireless Passive Intraocular Pressure Sensors", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents an implantable parylene-based wireless pressure sensor for biomedical pressure sensing applications specifically designed for continuous intraocular pressure (IOP) monitoring in glaucoma patients. It has an electrical LC tank resonant circuit formed by an integrated capacitor and an inductor coil to facilitate passive wireless sensing using an external interrogating coil connected to a readout unit. Two surface-micromachined sensor designs incorporating variable capacitor and variable capacitor/inductor resonant circuits have been implemented to realize the pressure-sensitive components. The sensor is monolithically microfabricated by exploiting parylene as a biocompatible structural material in a suitable form factor for minimally invasive intraocular implantation. Pressure responses of the microsensor have been characterized to demonstrate its high pressure sensitivity (> 7000 ppm/mmHg) in both sensor designs, which confirms the feasibility of pressure sensing with smaller than 1 mmHg of resolution for practical biomedical applications. A six-month animal study verifies the in vivo bioefficacy and biostability of the implant in the intraocular environment with no surgical or postoperative complications. Preliminary ex vivo experimental results verify the IOP sensing feasibility of such device. This sensor will ultimately be implanted at the pars plana or on the iris of the eye to fulfill continuous, convenient, direct, and faithful IOP monitoring.", "doi": "10.1109/JMEMS.2008.2004945", "issn": "1057-7157", "publisher": "IEEE", "publication": "Journal of Microelectromechanical Systems", "publication_date": "2008-12", "series_number": "6", "volume": "17", "issue": "6", "pages": "1342-1351" }, { "id": "authors:m7t2h-e7w19", "collection": "authors", "collection_id": "m7t2h-e7w19", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100726-104029245", "type": "article", "title": "Flexible parylene-based multielectrode array technology\n for high-density neural stimulation and recording", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Ameri", "given_name": "Hossein", "clpid": "Ameri-H" }, { "family_name": "Ahuja", "given_name": "Ashish K.", "clpid": "Ahuja-A-K" }, { "family_name": "Gutierrez", "given_name": "Christian", "clpid": "Gutierrez-C" }, { "family_name": "Lavrov", "given_name": "Igor", "clpid": "Lavrov-I" }, { "family_name": "Zhong", "given_name": "Hui", "clpid": "Zhong-Hui" }, { "family_name": "Menon", "given_name": "Parvathy R.", "clpid": "Menon-P-R" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord prosthetics. These arrays are microfabricated according to a single-metal-layer process and a revolutionary dual-metal-layer process that promises to meet the needs of extremely high-density stimulation applications. While in many cases thin-film platinum electrodes in parylene C would be sufficient, high surface-area platinum electroplating has been shown to extend the lifetime of stimulated electrodes to more than 430 million pulses without failing. Iridium electrode arrays with higher charge delivery capacity have also been fabricated using a new high-temperature stabilized parylene variant, parylene HT. In addition, a new heat molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and a chronic implantation study of the mechanical effects of parylene-based electrode arrays on the retina over a 6-month follow-up period has provided excellent results. Retinal stimulation from these parylene-based electrode arrays in an isolated tiger salamander preparation was shown to be comparable to light stimulation in terms of generation of action potentials in the inner retina. Finally, electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays.", "doi": "10.1016/j.snb.2007.10.069", "issn": "0925-4005", "publisher": "Elsevier", "publication": "Sensors and Actuators B: Chemical", "publication_date": "2008-06-16", "series_number": "2", "volume": "132", "issue": "2", "pages": "449-460" }, { "id": "authors:e35k2-qy340", "collection": "authors", "collection_id": "e35k2-qy340", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100708-110900771", "type": "article", "title": "An electrochemical intraocular drug delivery device", "author": [ { "family_name": "Li", "given_name": "Po-Ying", "clpid": "Li-Po-Ying" }, { "family_name": "Shih", "given_name": "Jason", "clpid": "Shih-Jason" }, { "family_name": "Lo", "given_name": "Ronalee", "clpid": "Lo-Ronalee" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Agrawal", "given_name": "Rajat", "clpid": "Agrawal-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" } ], "abstract": "A microelectromechanical systems (MEMS) drug delivery device is investigated for the treatment of incurable ocular diseases. Unlike conventional ocular drug delivery devices, this MEMS device is capable of being refilled, features electronic control of the drug regimen, and enables targeted intraocular drug delivery. The refillable design permits long-term drug therapy and avoids repetitive surgeries. Electronic control of dosing is achieved by using electrolysis-actuated pumping to deliver pharmaceuticals directly to the intraocular space. A flexible Parylene transscleral cannula allows targeted delivery to tissues in both the anterior and posterior segments of the eye. This electrochemically driven drug delivery device was demonstrated to provide flow rates suitable for ocular drug therapy (pL/min to \u03bcL/min). Both continuous and bolus drug delivery modes were performed to achieve accurate delivery of a target volume of 250 nL. An encapsulation packaging technique was developed for acute surgical studies and preliminary ex vivo drug delivery experiments in porcine eyes were performed.", "doi": "10.1016/j.sna.2007.06.034", "issn": "0924-4247", "publisher": "Elsevier", "publication": "Sensors and Actuators A", "publication_date": "2008-05-02", "series_number": "1", "volume": "143", "issue": "1", "pages": "41-48" }, { "id": "authors:vgczw-xd208", "collection": "authors", "collection_id": "vgczw-xd208", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:HANjbo08", "type": "article", "title": "Handheld forward-imaging needle endoscope for ophthalmic optical coherence tomography inspection", "author": [ { "family_name": "Han", "given_name": "Shuo", "clpid": "Han-Shuo" }, { "family_name": "Sarunic", "given_name": "Marinko V.", "clpid": "Sarunic-M-V" }, { "family_name": "Wu", "given_name": "Jigang", "clpid": "Wu-Jigang" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "abstract": "We report the narrowest to-date (21 gauge, 820-\u00b5m-diam) handheld forward-imaging optical coherence tomography (OCT) needle endoscope and demonstrate its feasibility for ophthalmic OCT inspection. The probe design is based on paired-angle-rotation scanning (PARS), which enables a linear B-scan pattern in front of the probe tip by using two counterrotating angle polished gradient-index (GRIN) lenses. Despite its small size, the probe can provide a numerical apertune (NA) of 0.22 and an experimental sensitivity of 92 dB at 0.5 frames. The feasibility of retinal imaging is tested on enucleated ex vivo porcine eyes, where structural features including remnant vitreous humor, retina, and choroid can be clearly distinguished. Due to its imaging quality comparable to a commercial OCT system and compatibility with the current ophthalmic surgery standard, the probe can potentially serve as a better alternative to traditional visual inspection by white light illumination during vitreoretinal surgery (e.g., vitrectomy).", "doi": "10.1117/1.2904664", "issn": "1083-3668", "publisher": "Society of Photo-Optical Instrumentation Engineers", "publication": "Journal of Biomedical Optics", "publication_date": "2008-03", "series_number": "2", "volume": "13", "issue": "2", "pages": "Art. No. 020505" }, { "id": "authors:va1ft-thn82", "collection": "authors", "collection_id": "va1ft-thn82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100813-083041941", "type": "book_section", "title": "Floating-disk parylene microvalve for self-regulating biomedical flow controls", "book_title": "MEMS 2008 Tucson : 21st IEEE International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "A novel self-regulating parylene micro valve is presented in this paper with potential applications for biomedical flow controls. Featuring a free-floating bendable valve disk and two-level valve seat, this surface-micromachined polymeric valve accomplishes miniature pressure/flow rate regulation in a band-pass profile stand-alone without the need of power sources or active actuation. Experimental data of underwater testing results have successfully demonstrated that the microfabricated in-channel valve can regulate water flow at 0-80 mmHg and 0-10 \u00b5L/min pressure/flow rate level, which is perfectly suitable for biomedical and lab-on-a-chip applications. For example, such biocompatible microvalve can be incorporated in ocular implants for control of eye fluid drainage to fulfill intraocular pressure (IOP) regulation in glaucoma patients.", "doi": "10.1109/MEMSYS.2008.4443721", "isbn": "978-1-4244-1792-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2008-01", "pages": "575-578" }, { "id": "authors:hjp2d-pdt23", "collection": "authors", "collection_id": "hjp2d-pdt23", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100722-110448277", "type": "book_section", "title": "Implantable parylene-based wireless intraocular pressure sensor", "book_title": "MEMS 2008 Tucson : 21st IEEE International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents a novel implantable, wireless,\npassive pressure sensor for ophthalmic applications. Two\nsensor designs incorporating surface-micromachined\nvariable capacitor and variable capacitor/inductor are\nimplemented to realize the pressure sensitive components.\nThe sensor is monolithically microfabricated using parylene\nas a biocompatible structural material in a suitable form\nfactor for increased ease of intraocular implantation.\nPressure responses of the microsensor are characterized\non-chip to demonstrate its high pressure sensitivity (> 7000\nppm/mmHg) with mmHg level resolution. An in vivo animal\nstudy verifies the biostability of the sensor implant in the\nintraocular environment after more than 150 days. This\nsensor will ultimately be implanted at the pars plana or iris of\nthe eye to fulfill continuous intraocular pressure (IOP)\nmonitoring in glaucoma patients.", "doi": "10.1109/MEMSYS.2008.4443592", "isbn": "978-1-4244-1792-6", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2008-01", "pages": "58-61" }, { "id": "authors:7ntdp-4ad41", "collection": "authors", "collection_id": "7ntdp-4ad41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:jmm07", "type": "article", "title": "Implantable micromechanical parylene-based pressure sensors for unpowered intraocular pressure sensing", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Agrawal", "given_name": "Rajat", "clpid": "Agrawal-R" }, { "family_name": "Saati", "given_name": "Saloomeh", "clpid": "Saati-S" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Varma", "given_name": "Rohit", "clpid": "Varma-R" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the first implantable, unpowered, parylene-based microelectromechanical system (MEMS) pressure sensor for intraocular pressure (IOP) sensing. From in situ mechanical deformation of the compliant spiral-tube structures, this sensor registers pressure variations without electrical or powered signal transduction of any kind. Micromachined high-aspect-ratio polymeric hollow tubes with different geometric layouts are implemented to obtain high-sensitivity pressure responses. An integrated device packaging method has been developed toward enabling minimally invasive suture-less needle-based implantation of the device. Both in vitro and ex vivo device characterizations have successfully demonstrated mmHg resolution of the pressure responses. In vivo animal experiments have also been conducted to verify the biocompatibility and functionality of the implant fixation method inside the eye. Using the proposed implantation scheme, the pressure response of the implant can be directly observed from outside the eye under visible light, with the goal of realizing convenient, direct and faithful IOP monitoring in glaucoma patients.", "doi": "10.1088/0960-1317/17/10/002", "issn": "0960-1317", "publisher": "IOP", "publication": "Journal of Micromechanics and Microengineering", "publication_date": "2007-10", "series_number": "10", "volume": "17", "issue": "10", "pages": "1931-1938" }, { "id": "authors:f97wx-v0c82", "collection": "authors", "collection_id": "f97wx-v0c82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:CHEjmems07", "type": "article", "title": "Surface-Micromachined Parylene Dual Valves for On-Chip Unpowered Microflow Regulation", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Meng", "given_name": "Ellis M.", "clpid": "Meng-E-M" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the world's first surface-micromachined parylene dual-valved microfluidic system for on-chip unpowered microflow regulation. Incorporating a normally closed and a normally open passive check valve in a back-to-back configuration inside a microchannel, the dual-valved system has successfully regulated the pressure/flow rate of air and liquid without power consumption or electronic/magnetic/thermal transduction. By exclusively using parylene C (poly-para-xylylene C) as the structural material, the fabricated valves have higher flexibility to shunt flows in comparison to other conventional thin-film valves. A state-of-the-art multilayer polymer surface-micromachining technology is applied here to fabricate parylene microvalves of various designs. The parylene-based devices are completely biocompatible/implantable and provide an economical paradigm for fluidic control in integrated lab-on-a-chip systems. Design, fabrication, and characterization of the parylene dual valves are discussed in this paper. Testing results have successfully demonstrated that the microflow regulation of the on-chip dual-valved system can achieve a bandpass profile in which the pressure control range is 0-50 mmHg with corresponding flow rates up to 2 mL/min for air flow and 1 muL/min flow rate for water flow. This regulation range is suitable for controlling biological conditions in human health care, with potential applications including drug delivery and regulation of elevated intraocular pressure (IOP) in glaucoma patients.", "doi": "10.1109/JMEMS.2006.889534", "issn": "1057-7157", "publisher": "IEEE", "publication": "Journal of Microelectromechanical Systems", "publication_date": "2007-04", "series_number": "2", "volume": "16", "issue": "2", "pages": "223-231" }, { "id": "authors:psdhm-zmm56", "collection": "authors", "collection_id": "psdhm-zmm56", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180716-112901034", "type": "book_section", "title": "Endoscopic optical coherence tomography of the retina at 1310 nm using paired-angle rotating scanning", "book_title": "Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine XI", "author": [ { "family_name": "Sarunic", "given_name": "Marinko V.", "clpid": "Sarunic-M-V" }, { "family_name": "Han", "given_name": "Shuo", "clpid": "Han-Shuo" }, { "family_name": "Wu", "given_name": "Jigang", "clpid": "Wu-Jigang" }, { "family_name": "Yaqoob", "given_name": "Zahid", "clpid": "Yaqoob-Z" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Yang", "given_name": "Changhuei", "orcid": "0000-0001-8791-0354", "clpid": "Yang-Changhuei" } ], "contributor": [ { "family_name": "Fujimoto", "given_name": "James G.", "clpid": "Fujimoto-J-G" }, { "family_name": "Izatt", "given_name": "Joseph A.", "clpid": "Izatt-J-A" }, { "family_name": "Tuchin", "given_name": "Valery V.", "clpid": "Tuchin-V-V" } ], "abstract": "Vitrectomy (removal of the vitreous humor) is an ophthalmic surgery required as a precursor to several posterior chamber procedures. Vitrectomy is commonly performed using an endoscopic vitreous cutter and fiber based light delivery for observation through a surgical microscope. Cross-sectional visualization of the retina and remnant vitreous layers during surgery using an external optical coherence tomography (OCT) scanner is impractical due to deformation in the shape of the eye and the cornea. We present a forward imaging probe with 820 &mgr;m outer diameter (21 gauge needle) for cross-sectional endoscopic OCT imaging during ophthalmic surgeries. The Paired-Angle-Rotating Scanner (PARS) OCT probe is based on angle polished gradient index (GRIN) lenses which are rotated about the optical axis. The scan pattern is determined by the angle between the GRIN lenses and the relative angular velocity. Endoscopic placement of the PARS-OCT probe tip near the retinal surface permits use of a longer wavelength light, in particular 1310 nm, which would otherwise suffer significant attenuation traversing the vitreous humor. The prototype endoscopic PARS-OCT probe is coupled to a commercially available 1310 nm swept laser source, and uses commercial software for data acquisition, processing, and display of retinal images in real time at an A-scan rate of 16 kHz. We present an analysis of aberrations due to off axis use of GRIN lenses and measure the scan pattern of the PARS probe. Images acquired on an ex vivo porcine retina are presented, motivating development of the endoscopic PARS-OCT probe for clinical evaluation.", "doi": "10.1117/12.701226", "isbn": "9780819465429", "publisher": "Society of Photo-optical Instrumentation Engineers (SPIE)", "place_of_publication": "Bellingham, WA", "publication_date": "2007-02-07", "pages": "Art. No. 642911" }, { "id": "authors:r54kb-3k010", "collection": "authors", "collection_id": "r54kb-3k010", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101112-151218275", "type": "book_section", "title": "Implantable Unpowered Parylene MEMS Intraocular Pressure Sensor", "book_title": "2006 International Conference on Microtechnologies in Medicine and Biology", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the first implantable, unpowered, parylene-based micro-electro-mechanical-systems (MEMS) pressure sensor for intraocular pressure (IOP) sensing. From in situ mechanical deformation of the compliant structures, this sensor registers pressure variations without power consumption/transduction. Micromachined high-aspect-ratio thin-walled tubes in different geometric layouts are exploited to obtain a high-sensitivity pressure response. An integrated packaging method has been successfully developed to realize suture-less implantation of the device. In vitro testing results have demonstrated that the IOP sensor can achieve 0.67 degree/mmHg angular sensitivity with a spiral-tube design, 3.43 \u00b5m/mmHg lateral sensitivity with a long-armed-tube design, and 0.38 \u00b5m/mmHg longitudinal sensitivity with a serpentine-tube design. This IOP sensor is designed to be implanted in the anterior chamber of the eye and anchored directly on the iris so that, under incident visible light, the pressure response of the implant can be directly observed from outside the eye, which enables faithful and unpowered IOP monitoring in glaucoma patients", "doi": "10.1109/MMB.2006.251543", "isbn": "978-1-4244-0337-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-05", "pages": "256-259" }, { "id": "authors:xhce1-0yr77", "collection": "authors", "collection_id": "xhce1-0yr77", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110720-113158743", "type": "book_section", "title": "Flexible Microfabricated Parylene Multielectrode Arrays for\n Retinal Stimulation and Spinal Cord Field Modulation", "book_title": "2006 International Conference on Microtechnologies in Medicine and Biology", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Fong", "given_name": "Andy J.", "clpid": "Fong-Andy-J" }, { "family_name": "Ameri", "given_name": "Hossein", "clpid": "Ameri-H" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Burdick", "given_name": "Joel W.", "clpid": "Burdick-J-W" }, { "family_name": "Roy", "given_name": "Roland R.", "clpid": "Roy-R-R" }, { "family_name": "Edgerton", "given_name": "V. Reggie", "clpid": "Edgerton-V-R" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "The first flexible parylene-based multielectrode arrays (MEAs) designed for functional electrical stimulation (FES) in retinal prostheses, and the extension of this technology toward enabling reflex-arc neuromodulation in cases of spinal cord damage or transection, are presented. A single metal layer 16 \u00d7 16 retinal electrode array of 125 \u03bcm-diameter thin-film Ti/Pt electrodes and lines\nof 12 \u03bcm-pitch has been fabricated as a demonstration of this technology. To allow for even higher density arrays, a novel dual-layer process has also been implemented that enables leads to pass under overlying electrodes without making electrical contact to them. A biomimetic parylene-based electrode array consisting of 1024 electrodes of highly variable spacing, 60 of which have been connected in this manner, has been fabricated according to this paradigm. A parylene-parylene annealing process has also been developed to increase device longevity under accelerated-lifetime saline soak conditions. Surgical tests of novel anatomically-conformal\ngeometries that enable such parylene-based electrode systems to interact with their neuronal targets of interest while causing minimal mechanical damage to tissues or to the implants are also presented. The use of these flexible electrode arrays in spinal cord stimulation experiments in animal models has proven their efficacy in stimulating neurons.", "doi": "10.1109/MMB.2006.251482", "isbn": "978-1-4244-0337-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-05", "pages": "31-34" }, { "id": "authors:9qnrx-fyb49", "collection": "authors", "collection_id": "9qnrx-fyb49", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110721-094836263", "type": "book_section", "title": "Flexible Parylene Packaged Intraocular Coil for Retinal Prostheses", "book_title": "Microtechnologies in Medicine and Biology", "author": [ { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-E-M" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "We present a flexible and fully-implantable coil designed for use as a power and data transfer component in retinal prosthesis applications. Compared with traditional hand-made intraocular coils, this microfabricated coil is flexible, with a 9.5 mm outer diameter and 10-mum-thick parylene C as the primary structural and packaging material. A post-fabrication heat treatment was used to improve the parylene package in order to protect the device in harsh corrosive environments such as the human eye. Long-term accelerated-lifetime soak testing in heated saline has been performed, and the mean time to failure (MTTF) of the parylene package extrapolated to 37\u00b0C was estimated using the Arrhenius relationship. The electrical failure of this device was also characterized by measuring the DC resistance in saline.", "doi": "10.1109/MMB.2006.251502", "isbn": "978-1-4244-0337-0", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2006-05", "pages": "105-108" }, { "id": "authors:v7gv1-sf387", "collection": "authors", "collection_id": "v7gv1-sf387", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110120-133620929", "type": "article", "title": "Unpowered spiral-tube parylene pressure sensor for intraocular pressure sensing", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the first biocompatible, unpowered, micromachined pressure sensor for intraocular pressure (IOP) sensing. This device is designed for implantation in the eye so that IOP can be faithfully measured externally. It features a parylene-based high-aspect-ratio spiral-tube structure fabricated using a buried-channel process. This passive sensor requires no power from other physical (i.e. electrical and/or magnetic) domains and registers pressure variations by changes of a mechanical in-plane spiral rotation that can be gauged by direct and convenient optical observation. The fabricated device has been tested in various media, and a 1 mm-radius device with a 10-turn spiral has successfully demonstrated continuous spiral rotation when immersed in liquids, with 0.22\u00b0/mmHg sensitivity in isopropyl alcohol (IPA) and 0.13\u00b0/mmHg sensitivity in water. This pressure sensing technology is proposed as a convenient method to monitor in situ IOP in glaucoma patients and to facilitate treatment and scientific study of the disease.", "doi": "10.1016/j.sna.2005.08.027", "issn": "0924-4247", "publisher": "Elsevier", "publication": "Sensors and Actuators A", "publication_date": "2006-03-13", "series_number": "2", "volume": "127", "issue": "2", "pages": "276-282" }, { "id": "authors:swwsa-gpp41", "collection": "authors", "collection_id": "swwsa-gpp41", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110218-111423210", "type": "book_section", "title": "Flexible Parylene-based Microelectrode Technology for Intraocular Retinal Prostheses", "book_title": "2006 1st IEEE International Conference on Nano/Micro Engineered and Molecular Systems", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Li", "given_name": "Wen", "clpid": "Li-Wen" }, { "family_name": "Ameri", "given_name": "Hossein", "clpid": "Ameri-H" }, { "family_name": "Ray", "given_name": "Aditi", "clpid": "Ray-A" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "We present the first single metal layer flexible microelectrode arrays designed for intraocular implantation that utilize parylene C as their primary structural and insulating material. These electrodes are fabricated as a key component of an intraocular retinal prosthesis comprising a radio-frequency coil for power and data transfer, a packaged high lead-count telemetry-recovery and driving application-specific integrated circuit (ASIC), and a high-density epiretinal stimulating microelectrode array for the treatment of retinal degenerative blindness in humans. Electrochemical tests have demonstrated that these thin-film platinum electrodes perform as necessary for neuronal stimulation. A novel bioconformal MEMS geometry for a complete intraocular system with capsular retaining-wings that enables all the components of the system to be implanted and retained within the lens capsule and vitreous cavity of the eye is also presented. The efficacy of this geometry when compared with a previous model without capsular retaining-wings has been verified by surgical implantation in animal models.", "doi": "10.1109/NEMS.2006.334886", "isbn": "1-4244-0139-9", "publisher": "IEEE", "place_of_publication": "Piscataway, N.J.", "publication_date": "2006-01", "pages": "743-746" }, { "id": "authors:hg3w1-a9z43", "collection": "authors", "collection_id": "hg3w1-a9z43", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190322-154442882", "type": "book_section", "title": "Progress Towards A High-Resolution Retinal Prosthesis", "book_title": "2005 IEEE Engineering in Medicine and Biology 27th Annual Conference", "author": [ { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Fink", "given_name": "Wolfgang", "clpid": "Fink-W" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Liu", "given_name": "Wentai", "clpid": "Liu-Wentai" }, { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Tarbell", "given_name": "Mark", "clpid": "Tarbell-M-A" } ], "abstract": "Simulations of artificial vision suggest that 1000 electrodes may be required to restore vision to individuals with diseases of the outer retina. In order to achieve such an implant, new technology is needed, since the state-of-the-art implantable neural stimulator has at most 22 contacts with neural tissue. Considerable progress has been made towards that goal with the development of image processing, microelectronics, and polymer based electrodes and interconnects. An image processing system has been realized that is capable of real-time implementation of image decimation and filtering (for example, edge detection). Application specific integrated circuits (ASICs) have been designed and tested to demonstrate closed loop power control and efficient microstimulation. A novel packaging process has been developed that is capable of simultaneously forming a receiver coil, interconnects, and stimulating electrodes.", "doi": "10.1109/IEMBS.2005.1616215", "isbn": "0-7803-8741-4", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2005-09", "pages": "7373-7375" }, { "id": "authors:s4cny-twg34", "collection": "authors", "collection_id": "s4cny-twg34", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110825-150721909", "type": "book_section", "title": "Scalable flexible chip-level parylene package for high lead count retinal prostheses", "book_title": "Transducers '05 : 13th International Conference on Solid-State Sensors, Actuators, and Microsystems", "author": [ { "family_name": "Rodger", "given_name": "Damien C.", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Weiland", "given_name": "James D.", "clpid": "Weiland-J-D" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "We present an innovative technology for the fabrication of a biocompatible parylene-based high lead count retinal prosthesis in which a prefabricated stand-alone application-specific integrated circuit (ASIC) is placed directly into the fabrication process of the other system components. The package is fabricated in such a way that the ASIC-to-electrode interconnects are patterned using standard photolithography. The density of interconnects is fully scalable to the limits of lithography. This packaging scheme also enables the simultaneous integration and interconnection of discrete components such as chip capacitors with the rest of the system. Electrical test results verify the efficacy of this cost-effective and high-yield packaging scheme, and pave the way for a monolithic implantable parylene-based intraocular system.", "doi": "10.1109/SENSOR.2005.1497487", "isbn": "0-7803-8994-8", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2005-06", "pages": "1973-1976" }, { "id": "authors:8jmtq-2xe10", "collection": "authors", "collection_id": "8jmtq-2xe10", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110818-114326452", "type": "book_section", "title": "Implantable parylene MEMS for glaucoma therapy", "book_title": "Proceedings of the 3rd Annual International IEEE EMBS Special Topic Conference on Microtechnologies in Medicine and Biology", "author": [ { "family_name": "Meng", "given_name": "Ellis", "clpid": "Meng-Ellis-M" }, { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien", "clpid": "Rodger-D" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Humayun", "given_name": "Munir", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "An implantable glaucoma management system is presented for the first time. Glaucoma is an incurable disease characterized by gradual visual field loss that eventually results in blindness. Studies indicate that reduction of intraocular pressure reduces the rate of disease progress. A passive parylene MEMS pressure sensor and drainage shunt comprise a complete system for the detection and alleviation of elevated intraocular pressure. Tissue anchors for securing the pressure sensor to the iris have been developed to facilitate direct and convenient optical monitoring of intraocular pressure.", "doi": "10.1109/MMB.2005.1548399", "isbn": "0-7803-8711-2", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2005-05", "pages": "116-119" }, { "id": "authors:pbpwr-1zv59", "collection": "authors", "collection_id": "pbpwr-1zv59", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110609-114150828", "type": "book_section", "title": "Spiral-Tube Parylene Intraocular Pressure Sensor", "book_title": "MEMS 2005 Miami : 18th IEEE International Conference on Micro Electro Mechanical Systems", "author": [ { "family_name": "Chen", "given_name": "Po-Jui", "clpid": "Chen-Po-Jui" }, { "family_name": "Rodger", "given_name": "Damien", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Humayun", "given_name": "Mark S.", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Tai", "given_name": "Yu-Chong", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" } ], "abstract": "This paper presents the first biocompatible, all-mechanical, micromachined pressure sensor with a high-aspect-ratio spiral-tube structure fabricated through a one-layer parylene process. This passive sensor has zero power consumption and indicates the pressure variation by changes of in situ in-plane spiral rotation, which can be gauged externally by a direct and convenient optical observation. A 1 mm-radius device with a 10-turn spiral has demonstrated a 0.22 degree/mmHg sensitivity in liquid. This device is designed for eye implantation and the intraocular spiral rotation can be recorded from outside of the eye. Such a sensing technology is proposed to monitor the intraocular pressure in glaucoma patients.", "doi": "10.1109/MEMSYS.2005.1453929", "isbn": "0-7803-8732-5", "publisher": "IEEE", "place_of_publication": "Piscataway, NJ", "publication_date": "2005", "pages": "311-314" }, { "id": "authors:bp08b-vh778", "collection": "authors", "collection_id": "bp08b-vh778", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:KAZembc04", "type": "book_section", "title": "A test microchip for evaluation of hermetic packaging technology for biomedical prosthetic implants", "book_title": "International Conference of the IEEE Engineering in Medicine and Biology Society, 26th (IEMBS '04), San Francisco, CA, 1-5 September 2004", "author": [ { "family_name": "Kazemi", "given_name": "Mohammad", "clpid": "Kazemi-M" }, { "family_name": "Basham", "given_name": "Eric", "clpid": "Basham-E" }, { "family_name": "Sivaprakasam", "given_name": "Mohanasankar", "clpid": "Sivaprakasam-M" }, { "family_name": "Wang", "given_name": "Guoxing", "clpid": "Wang-Guoxing" }, { "family_name": "Rodger", "given_name": "Damien", "orcid": "0000-0002-1583-5946", "clpid": "Rodger-D-C" }, { "family_name": "Weiland", "given_name": "James", "clpid": "Weiland-J" }, { "family_name": "Tai", "given_name": "Y. C.", "orcid": "0000-0001-8529-106X", "clpid": "Tai-Yu-Chong" }, { "family_name": "Liu", "given_name": "Wentai", "clpid": "Liu-Wentai" }, { "family_name": "Humayun", "given_name": "Mark", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" } ], "abstract": "The development of a test chip that will be used to evaluate a hermetic and biocompatible package for the\ndriving CMOS circuitry of a retinal prosthesis is described.\nThe package design is estimated to be about 2 x 2 x 0.3 mm^3\nand will be formed by conformal layers of parylene and a metal (e.g. titanium) as inner and outer protections, respectively. The test chip has been specifically designed for evaluation of the packaging technology. It consists of many blocks of analog and digital components as well as relative humidity and temperature sensors. The test chip has more probe points than a typical chip, allowing a more thorough evaluation of circuit behavior during the testing. This chip will first be coated in a layer of parylene C and soaked in heated isotonic saline for an extended period of time. Every block in the chip will then be tested for functionality using the surface probe points. The next\nstep is to coat the surface of another test chip with parylene and a metal and repeat these soak tests. The results will then be analyzed and mean time-to-failure for the different samples will then be computed. Using the accelerated testing paradigm, these results will then be extrapolated to mean time-to-failure in the operating intraocular environment. Parylene test structures have already undergone an accelerated lifetime test\nand results have been analyzed.", "doi": "10.1109/IEMBS.2004.1404142", "isbn": "0-7803-8439-3", "publisher": "IEEE", "place_of_publication": "Piscataway, Nj", "publication_date": "2004-09", "pages": "4093-4095" }, { "id": "authors:8h1q3-r8276", "collection": "authors", "collection_id": "8h1q3-r8276", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200309-161405106", "type": "article", "title": "Passage of Heme-Iron Across the Envelope of Staphylococcus aureus", "author": [ { "family_name": "Mazmanian", "given_name": "Sarkis K.", "orcid": "0000-0003-2713-1513", "clpid": "Mazmanian-S-K" }, { "family_name": "Skaar", "given_name": "Eric P.", "clpid": "Skaar-E-P" }, { "family_name": "Gaspar", "given_name": "Andrew H.", "clpid": "Gaspar-A-H" }, { "family_name": "Humayun", "given_name": "Munir", "orcid": "0000-0002-5830-5208", "clpid": "Humayun-M-S" }, { "family_name": "Gornicki", "given_name": "Piotr", "clpid": "Gornicki-P" }, { "family_name": "Jelenska", "given_name": "Joanna", "clpid": "Jelenska-J" }, { "family_name": "Joachmiak", "given_name": "Andrezj", "clpid": "Joachmiak-A" }, { "family_name": "Missiakas", "given_name": "Dominique M.", "clpid": "Missiakas-D-M" }, { "family_name": "Schneewind", "given_name": "Olaf", "clpid": "Schneewind-O" } ], "abstract": "The cell wall envelope of Gram-positive pathogens functions as a scaffold for the attachment of virulence factors and as a sieve that prevents diffusion of molecules. Here the isdgenes (iron-regulated surface determinant) of Staphylococcus aureus were found to encode factors responsible for hemoglobin binding and passage of heme-iron to the cytoplasm, where it acts as an essential nutrient. Heme-iron passage required two sortases that tether Isd proteins to unique locations within the cell wall. Thus, Isd appears to act as an import apparatus that uses cell wall\u2013anchored proteins to relay heme-iron across the bacterial envelope.", "doi": "10.1126/science.1081147", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2003-02-07", "series_number": "5608", "volume": "299", "issue": "5608", "pages": "906-909" } ]