Jeong Oen Lee

Biocompatible Multifunctional Black-Silicon for Implantable Intraocular Sensor

Multifunctional black-silicon (b-Si) integrated on the surface of an implantable intraocular pressure sensor significantly improves sensor performance and reliability in six-month in vivo studies. The antireflective properties of b-Si triples the signal-to-noise ratio and increases the optical readout distance to a clinically viable 12 cm. Tissue growth and inflammation response on the sensor is suppressed demonstrating desirable anti-biofouling properties.

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3N4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation.A nanostructured membrane inspired by transparent butterfly wings is used for intraocular pressure sensing in vivo.

A microscale optical implant for continuous in vivo monitoring of intraocular pressure

Intraocular pressure (IOP) is a key clinical parameter in glaucoma management. However, despite the potential utility of daily measurements of IOP in the context of disease management, the necessary tools are currently lacking, and IOP is typically measured only a few times a year. Here we report on a microscale implantable sensor that could provide convenient, accurate, on-demand IOP monitoring in the home environment. When excited by broadband near-infrared (NIR) light from a tungsten bulb, the sensor’s optical cavity reflects a pressure-dependent resonance signature that can be converted to IOP. NIR light is minimally absorbed by tissue and is not perceived visually. The sensor’s nanodot-enhanced cavity allows for a 3–5 cm readout distance with an average accuracy of 0.29 mm Hg over the range of 0–40 mm Hg. Sensors were mounted onto intraocular lenses or silicone haptics and secured inside the anterior chamber in New Zealand white rabbits. Implanted sensors provided continuous in vivo tracking of short-term transient IOP elevations and provided continuous measurements of IOP for up to 4.5 months.

Black silicon as a multifunctional material for medical implants: First demonstrated use in in-vivo intraocular pressure sensing

We report the first in vivo demonstrated use of multifunctional black silicon (b-Si) on medical implants. B-Si is integrated onto the surface of a highly miniaturized sub-mm implantable intraocular pressure (IOP) sensor. This integration has significantly improved sensor signal-to-noise ratio (SNR) through the suppression of background noise as well as durability through minimized device biofouling. The incorporation of b-Si has enabled the use of a slit-lamp, the most widely used clinical ophthalmic microscope, for real-time IOP measurements on fully awake rabbits at a world-record 12-cm readout distance. Furthermore, b-Si has shown remarkable antifouling properties during a 6-month in vivo study by minimizing tissue proliferation and encapsulation on the ocular implant, promising much improved long-term implant serviceability.

Real-Time In Vivo Intraocular Pressure Monitoring Using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments, and improves the overall practicality of the optical IOP-monitoring approach.

Achieving clinically viable 12-CM readout distance from micromachined implantable intraocular pressure sensor using a standard clinical slit lamp

Achieving a practical readout distance for implantable intraocular pressure (IOP) sensors is an essential step toward commercialization yet has remained as a major challenge. Using the Zeiss SL-30 slit lamp - a standard ophthalmic scope widely used by clinicians, we have demonstrated an optical readout distance of 12 cm from a micromachined IOP sensor implanted in an ex-vivo rabbit eye. We show that we have achieved this readout distance by (1) redesigning the sensing area of the IOP sensor and its fabrication steps to significantly improve the signal-to-noise ratio; and (2) incorporating a novel robust detection algorithm, which includes a much-improved opto-mechanical model, that allows us to remove the background noise and instantaneously map the sensors optical signal to the corresponding IOP value. A significant increase in readout distance accomplished using a well established ophthalmic clinical scope makes our IOP system a more clinically viable choice.

Effect of optical aberrations on intraocular pressure measurements using a microscale optical implant in ex vivo rabbit eyes

Abstract. Elevated intraocular pressure (IOP) is the only modifiable major risk factor of glaucoma. Recently, accurate and continuous IOP monitoring has been demonstrated in vivo using an implantable sensor based on optical resonance with remote optical readout to improve patient outcomes. Here, we investigate the relationship between optical aberrations of ex vivo rabbit eyes and the performance of the IOP sensor using a custom-built setup integrated with a Shack–Hartmann sensor. The sensor readouts became less accurate as the aberrations increased in magnitude, but they remained within the clinically acceptable range. For root-mean-square wavefront errors of 0.10 to 0.94  μm, the accuracy and the signal-to-noise ratio were 0.58  ±  0.32  mm Hg and 15.57  ±  4.85  dB, respectively.

Glucose measurement using Surface Enhanced Raman Scattering

Summary form only given. Surface Enhanced Raman Scattering (SERS) has a great potential to serve as a monitoring technology for biomolecules, but sensing biomolecules for practical purposes have remained challenging for two reasons. One of the challenges is securing SERS substrates with uniform spatial enhancement that is crucial for quantitative measurements, and the other is finding proper linker molecules that will promote the surface enhancement. To address these challenges, we have been developing a new approach of using highly sensitive surface enhanced Raman scattering (SERS) platform for glucose sensing. In the presentation, I will discuss the fabrication of high performance 3D SERS substrate based on straightforward, two successive wet chemical processes, with experimentally proven strong enhancement and excellent spatial uniformity as well as the use of new linker molecules for making glucose-specific SERS substrates and their use in performing quantitative glucose measurements. Glucose sensing results from different development stages will be discussed.

In vivo intraocular pressure measurements using a miniaturized nanophotonics-enhanced sensor implant

Glaucoma is the leading causes of blindness, affecting an estimated 70 million individuals in the world. Because an elevated intraocular pressure (IOP) has been identified as a major risk factor, current therapies are aimed at lowering eye pressure. Consequently, monitoring of IOP is the most important tool in diagnosis and management of glaucoma. However current pressure measurement approaches have many challenges: measurements are obtained at the doctors office only every few months, and it is difficult to develop more effective, custom-tailored optimal disease management for individual patients. To address this challenge, a number of efforts have been made to develop implantable IOP sensors based on electrical readout methods, yet further miniaturization, improved readout distance, and signal-tonoise ratio (SNR) are still desired. In this presentation, I will present a compact, implantable nanophotonic pressure sensor with remote optical readout. The sensor has provided robust measurements of hydrostatic pressure between 0-40mmHg and performed well on table top characterizations, ex-vivo, and in-vivo measurements. Sensor design, fabrication, & characterizations; implantation preparation and procedures, and short-term & long-term in-vivo monitoring will be discussed.

Efficient power generation from vocal folds vibrations for medical electronic implants

The availability of practical, implantable, efficient power generators will proliferate the use of medical electronic implants that can be very useful for treating and managing various medical conditions. Using a vibration-driven power generator, we have successfully generated 0.3-mW/cm2 of electric power continuously from the acousto-mechanical vibrations that originate from the human vocal folds and propagate along the skeletal frame and air passage throughout the head and neck. Our energy harvesters are highly efficient because vocal vibrations excite them at their designed resonant frequencies at 100 and 200 Hz, which are the dominant vocal vibrations of men and women, respectively. In addition, we use laser micromachining to pattern single crystal lead-zirconate-titanate (PZT) sheets for better efficiency. Our harvesters are designed to fit into a square area (1×1 cm2 or smaller) so that they can form a flexible large array to generate more power.