Saloomeh Saati

Microfabricated Implantable Parylene-Based Wireless Passive Intraocular Pressure Sensors

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.[2008-0111].

Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant

This paper presents an implant-based wireless pressure sensing paradigm for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. An implantable parylene-based pressure sensor has been developed, featuring an electrical LC-tank resonant circuit for passive wireless sensing without power consumption on the implanted site. The sensor is microfabricated with the use of parylene C (poly-chloro-p-xylylene) to create a flexible coil substrate that can be folded for smaller physical form factor so as to achieve minimally invasive implantation, while stretched back without damage for enhanced inductive sensor-reader coil coupling so as to achieve strong sensing signal. A data-processed external readout method has also been developed to support pressure measurements. By incorporating the LC sensor and the readout method, wireless pressure sensing with 1-mmHg resolution in longer than 2-cm distance is successfully demonstrated. Other than extensive on-bench characterization, device testing through six-month chronic in vivo and acute ex vivo animal studies has verified the feasibility and efficacy of the sensor implant in the surgical aspect, including robust fixation and long-term biocompatibility in the intraocular environment. With meeting specifications of practical wireless pressure sensing and further reader development, this sensing methodology is promising for continuous, convenient, direct, and faithful IOP monitoring.

MINI DRUG PUMP FOR OPHTHALMIC USE

Purpose: To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use. Methods: Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the bench-top and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 × 7.7 × 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma aqueous drainage device. To determine the ability to refill and also the patency of the cannula, at intervals of 4–6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 µL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed by slit lamp examination, photography, and fluorescein angiography. Results: Bench-top testing showed 2.0 µL/min delivery when using 0.4 mW of power for electrolysis. One-way valves showed reliable opening pressures of 470 mmHg. All implanted devices refilled at 4–6 weeks intervals for 4–6 months. No infection was seen. No devices extruded. No filtering bleb formed over the implant. Conclusions: A prototype ocular mini drug pump was built, implanted, and refilled. Such a platform needs more testing to determine the long term biocompatibility of an electrically-controlled implanted pump. Testing with various pharmacological agents is needed to determine its ultimate potential for ophthalmic use.

Implantable micromechanical parylene-based pressure sensors for unpowered intraocular pressure sensing

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.

Implantable parylene-based wireless intraocular pressure sensor

This paper presents a novel implantable, wireless, passive pressure sensor for ophthalmic applications. Two sensor designs incorporating surface-micromachined variable capacitor and variable capacitor/inductor are implemented to realize the pressure sensitive components. The sensor is monolithically microfabricated using parylene as a biocompatible structural material in a suitable form factor for increased ease of intraocular implantation. Pressure responses of the microsensor are characterized on-chip to demonstrate its high pressure sensitivity (> 7000 ppm/mmHg) with mmHg level resolution. An in vivo animal study verifies the biostability of the sensor implant in the intraocular environment after more than 150 days. This sensor will ultimately be implanted at the pars plana or iris of the eye to fulfill continuous intraocular pressure (IOP) monitoring in glaucoma patients.

High-Density Flexible Parylene-Based Multielectrode Arrays for Retinal and Spinal Cord Stimulation

Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord applications. These electrode arrays are microfabricated according to single-metal-layer and, most recently, dual-metal-layer processes. A new heat-molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and chronic implantation studies have been undertaken to study the mechanical effects of parylene-based prostheses on the retina, with excellent results to date. 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.

Noninvasive assessment of retinal vascular oxygen content among normal and diabetic human subjects: a study using hyperspectral computed tomographic imaging spectroscopy.

Purpose: This pilot study was aimed to demonstrate the clinical feasibility of using hyperspectral computed tomographic spectroscopy to measure blood oxygen content in human retinal vessels. Methods: All procedures were performed under a University of Southern California Institutional Review Board–approved protocol and after obtaining informed consent. Fifty-seven subjects with and without diabetic retinopathy were dilated for standard fundus photography. Fundus photographs and retinal vascular oxygen measurements (oximetry) were made using a custom-made hyperspectral computed tomographic imaging spectrometer coupled to a standard fundus camera. Oximetry measurements were made along arteries (Aox) and veins (Vox) within vessel segments that were 1 to 2 disk diameters from the optic disk. Results: For all control subjects (n = 45), mean Aox and Vox were 93 ± 7% and 65 ± 5% (P = 0.001), respectively. For all diabetic subjects (n = 12), mean Aox and Vox were 90 ± 7% and 68 ± 5% (P = 0.001), respectively. In subjects with proliferative diabetic retinopathy, Aox was significantly lower, and Vox was significantly higher than other groups (85 ± 4% and 71 ± 4%, respectively; P = 0.04, analysis of variance). There was a highly significant difference in the arteriovenous difference between subjects with proliferative diabetic retinopathy and those in the control group (14 vs. 26%, P = 0.003). Conclusion: Hyperspectral computed tomographic spectroscopy is a clinically feasible method for measurement and analysis of vascular oxygen content in retinal health and disease. This study uses the techniques relevant to oximetry; however, the breadth of spectral data available through this method may be applicable to study other anatomical and functional features of the retina in health and disease.

Implantable Flexible-Coiled Wireless Intraocular Pressure Sensor

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.

Acute Variations in Retinal Vascular Oxygen Content in a Rabbit Model of Retinal Venous Occlusion

Purpose To study the variation in intravascular oxygen saturation (oximetry) during an acute retinal vein occlusion (RVO) using hyperspectral computed tomographic spectroscopy based oximetry measurements. Methods Thirty rabbits were dilated and anesthetized for experiments. Baseline oximetry measurements were made using a custom-made hyperspectral computed tomographic imaging spectrometer coupled to a fundus camera. RVO were induced using argon green laser following an intravenous injection of Rose Bengal. RVO induction was confirmed by fluorescein angiography. Retinal oximetry measurements were repeated in arterial and venous branches one hour after RVO induction and up to 4 weeks afterwards. Comparison of retinal oximetry before and after vein occlusion was made using the Student T-test. Results One hour after RVO induction, we observed statistically significant reductions in the intravascular oxygen saturation in temporal retinal arteries (85.1±6.1% vs. 80.6±6.6%; p<0.0001) and veins (71.4±5.5% vs. 64.0±4.7%; p<0.0001). This decrease was reversible in animals that spontaneously recannulated the vein occlusion. There were no statistically significant differences in oxygen saturation in the nasal control arteries and veins before and after temporal vein RVO induction. Conclusions We demonstrate, for the first time, acute changes in the intravascular oxygen content of retinal vessels 1 hour after RVO. These changes are reversible upon spontaneous recannulation of retinal vessels. This study demonstrates that hyperspectral computer tomographic spectroscopy based oximetry can detect physiological variations in intravascular retinal oxygen saturation. The study also provides the first qualitative and quantitative evidence of the variation in retinal vascular oxygen content directly attributable to an acute retinal vein occlusion.

Ex Vivo implantation study of minimally invasive glaucoma drainage device

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 10–20 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.