Ruiqi Long

Optofluidic phantom mimicking optical properties of porcine livers.

One strategy for assessing efficacy of a liver transplant is to monitor perfusion and oxygenation after transplantation. An implantable optical sensor is being developed to overcome inadequacies of current monitoring approaches. To facilitate sensor design while minimizing animal use, a polydimethylsiloxane (PDMS)-based liver phantom was developed to mimic the optical properties of porcine liver in the 630-1000 nm wavelength range and the anatomical geometry of liver parenchyma. Using soft lithography to construct microfluidic channels in pigmented elastomer enabled the 2D approximation of hexagonal liver lobules with 15mm sinusoidal channels, which will allow perfusion with blood-mimicking fluids to facilitate the development of the liver perfusion and oxygenation monitoring system.

Optimizing probe design for an implantable perfusion and oxygenation sensor

In an effort to develop an implantable optical perfusion and oxygenation sensor, based on multiwavelength reflectance pulse oximetry, we investigate the effect of source–detector separation and other source-detector characteristics to optimize the sensor’s signal to background ratio using Monte Carlo (MC) based simulations and in vitro phantom studies. Separations in the range 0.45 to 1.25 mm were found to be optimal in the case of a point source. The numerical aperture (NA) of the source had no effect on the collected signal while the widening of the source spatial profile caused a shift in the optimal source-detector separation. Specifically, for a 4.5 mm flat beam and a 2.4 mm × 2.5 mm photodetector, the optimal performance was found to be when the source and detector are adjacent to each other. These modeling results were confirmed by data collected from in vitro experiments on a liver phantom perfused with dye solutions mimicking the absorption properties of hemoglobin for different oxygenation states.

Optimizing source detector separation for an implantable perfusion and oxygenation sensor

Each year thousands of patients are added to the waiting list for liver transplants. The first 7-10 days after transplant have proven to be the most critical in patient recovery and it is hypothesized that monitoring organ vital signals in this period can increase patient and graft survival rates. An implantable sensor to monitor the organ perfusion and oxygenation signals following surgery is being developed by our group. The sensor operates based on measuring diffuse reflection from three light emitting diodes (735, 805 and 940 nm). In this work the optimal source detector spacing to maximize oxygenation signal level is investigated for a portal vein model. Monte Carlo simulations provided signal levels and corresponding penetration depths as a function of separation between a point optical source and detector. The modeling results indicated a rapid decay in the optical signal with increasing distance. Through further analysis, it was found that there exists an optimal range of point source to detector spacing, between roughly 1 and 2 mm, in which the blood signal from the simulated portal vein was maximized. Overall, these results are being used to guide the placement and configuration of our probe for in vivo animal studies.

Optical instrument design for interrogation of dermally-implanted luminescent microparticle sensors

Luminescence-based sensors have been developed in microparticle formats for biochemical targets such as glucose, enabling use of dermal implants for on-demand monitoring. For these to be deployed and interrogated in vivo, a matched optoelectronic system for delivery of excitation, collection and analysis of luminescence response is needed. In this work, simulations based on Monte Carlo ray-tracing were performed for models of luminescent microparticle materials embedded in skin. The spectral and spatial distribution of luminescence escaping the skin was determined for different concentrations, implantation depths, and input beam sizes. Results indicate that the implant environment does not significantly alter the measured spectral intensity ratios. The escaping emission light possesses measurable power and spectral information for quantitative analysis. Using these findings, an optical system has been designed specifically for sensor interrogation and response acquisition, and is currently implemented in hardware. Following benchtop validation and signal-to-noise maximization with tissue phantoms, the instrument will be used for measurement on sensors in rat subjects.

Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma

An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.

Three-dimensional, multiwavelength Monte Carlo simulations of dermally implantable luminescent sensors

Dermally implanted luminescent sensors have been proposed for monitoring of tissue biochemistry, which has the potential to improve treatments for conditions such as diabetes and kidney failure. Effective in vivo monitoring via noninvasive transdermal measurement of emission from injected microparticles requires a matched optoelectronic system for excitation and collection of luminescence. We applied Monte Carlo modeling to predict the characteristics of output luminescence from microparticles in skin to facilitate hardware design. Three-dimensional, multiwavelength Monte Carlo simulations were used to determine the spatial and spectral distribution of the escaping luminescence for different implantation depths, excitation light source properties, particle characteristics, and particle packing density. Results indicate that the ratio of output emission to input excitation power ranged 10(-3) to 10(-6) for sensors at the upper and lower dermal boundaries, respectively, and 95% of the escaping emission photons induced by a 10-mm-diam excitation beam were confined within an 18-mm circle. Tightly packed sensor configurations yielded higher output intensity with fewer particles, even after luminophore concentration effects were removed. Most importantly, for the visible wavelengths studied, the ability to measure spectral changes in emission due to glucose changes was not significantly affected by absorption and scattering of tissue, which supports the potential to accurately track changes in luminescence of sensor implants that respond to the biochemistry of the skin.

Experimental validation of an optical system for interrogation of dermally-implanted microparticle sensors

Dermally-implanted microparticle sensors are being developed for on-demand monitoring of blood sugar levels. For these to be deployed in vivo, a matched optoelectronic system for delivery of excitation, collection and analysis of escaping fluorescent signal is needed. Previous studies predicted the characteristics of fluorescence from microparticle sensors to facilitate design of hardware system. Based on the results of simulations, we designed and constructed the optical part of this opto-electronic system. This study experimentally verified the simulation results and tested the capability of the designed optical system. Reliable skin phantoms sufficient for future dynamic tests were developed. Skin phantoms with different thicknesses were made and the optical properties of skin phantoms were determined with an integrating sphere system and Inverse Adding-Doubling method. Measurements of sensor emission spectrum through phantoms with different thicknesses were done with the designed optical system. Simulations for the experiment situation were performed. The experimental measurements agreed well with simulations in most cases. The results of hardware experiment and validation with skin phantoms provided us with critical information for future dynamic tests and animal experiments.

In vitro performance of a perfusion and oxygenation optical sensor using a unique liver phantom

Between the years 1999 and 2008, on average 2,052 people died per year on the waiting list for liver transplants. Monitoring perfusion and oxygenation in transplanted organs in the 7 to 14 days period post-transplant can enhance graft and patient survival rates, and resultantly increase the availability of organs. In this work, we present in vitro results using a unique liver phantom that support the ability of our sensor to detect perfusion changes in the portal vein at low levels (50 mL/min . 4.5% of normal level). Our sensor measures diffuse reflection from three wavelengths (735, 805 and 940 nm) around the hemoglobin isobestic point (805 nm) to determine perfusion and oxygenation separately. To assess the sensitivity of our sensor to flow changes in the low range, we used two peristaltic pumps to pump a dye solution mimicking the optical properties of oxygenated blood, at various rates, through a PDMS based phantom mimicking the optical properties of liver tissue. The collected pulsatile signal increased by 120% (2.2X) for every 100 mL/min flow rise for all three wavelengths in the range 50 to 500 mL/min. In addition, we used different dye mixtures to mimic oxygenation changes at constant perfusion/flow levels. The optical properties of the dye mixtures mimic oxygen saturations ranging between 0 and 100%. The sensor was shown to be sensitive to changes in oxygen saturations above 50%.

High-efficiency optical systems for interrogation of dermally-implanted sensors

Ratiometric Luminescent microparticle sensors have been developed for sensing biochemical targets such as glucose in interstitial fluid, enabling use of dermal implants for on-demand monitoring. For these sensor systems to be deployed in vivo, a matched optoelectronic system for interrogation of dermally-implanted sensors was previously designed, constructed, and evaluated experimentally. During evaluation experiments, it revealed that the system efficiency was compromised by losses due to fiber connections, the entrance aperture, and the entrance slit of the spectrometer. In this work, two optimization methods were investigated to overcome photon loss at fiber connections and internal trade-off between resolution and input light power of the current spectrometer: 1) Replacement of the CCD spectrometer with a two-detector system, enabling extraction of key spectral information by integrating signals over two wavelength regions (reference and sensing emission peaks); and 2) Free-space coupling of the optical probe to a custom low-resolution spectrometer. Photon loss was evaluated by experiments and simulations, preliminary hardware of two-detector system was constructed, and optimization simulations were performed to explore conceptual feasibility of the free-space coupling custom-designed spectrometer.

Stability of response and in vivo potential of microparticle glucose sensors

We have developed novel combinations of glucose receptors, luminescent molecules, and nanoengineered materials to enable accurate and sensitive determination of glucose using microparticles. This paper will report the results of modeling and experimental work to determine two key properties of these systems: (1) maximal stability of the response under continuous operation; (2) maximal efficiency of transdermal excitation and collection of emission.