Wearable Microsystem for Minimally Invasive, Pseudo-Continuous Blood Glucose Monitoring: The e-Mosquito.

This paper presents a wearable microsystem for minimally invasive, autonomous, and pseudo-continuous blood glucose monitoring, addressing a growing demand for replacing tedious fingerpricking tests for diabetic patients. Unlike prevalent solutions which estimate blood glucose levels from interstitial fluids or tears, our design extracts a whole blood sample from a small lanced skin wound using a novel shape memory alloy (SMA)-based microactuator and directly measures the blood glucose level from the sample. In vitro characterization determined that the SMA microactuator produced penetration force of 225 gf, penetration depth of 3.55 mm, and consumed approximately 5.56 mW·h for triggering. The microactuation mechanism was also evaluated by extracting blood samples from the wrist of four human volunteers. A total of 19 out of 23 actuations successfully reached capillary vessels below the wrists producing blood droplets on the surface of the skin. The integrated potentiostat-based glucose sensing circuit of our e-Mosquito device also showed a good linear correlation (R2 = 0.9733) with measurements using standard blood glucose monitoring technology. These proof-of-concept studies demonstrate the feasibility of the e-Mosquito microsystem for autonomous intermittent blood glucose monitoring.

CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.

Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 µm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and µSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 µW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 µA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS.

Catheter-based acoustic interrogation device for real-time monitoring of the dynamics of the lower esophageal sphincter: in vitro and pilot canine studies.

This paper presents a novel minimally-invasive catheter-based acoustic interrogation device for real-time monitoring the dynamics of the lower esophageal sphincter (LES). Dysfunction of the LES could result gastrointestinal (GI) diseases, such as gastroesophageal reflux disease (GERD). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the LES to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be monitored. The device was tested in vitro by utilizing a custom-designed LES simulator, as well as in vivo in a pilot canine model. In the in vitro test, the sound was captured by the microphone and its strength was correlated with the level of LES opening and closing which was controlled by the simulator. The measurements showed statistically significant (p < 0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, DOF = 9). In the in vivo test, the LES was forced open and closed by a transoral endoscope, which was monitored in real-time by a transpyloric endoscope inserted from the duodenum and positioned into the distal stomach. Frame-by-frame video analysis validated the interrelation between the sound strength and the LES opening and closing. The LES dynamics monitored by the proposed device has the potential to become a valuable minimally-invasive technique for understanding LES dysfunction.

Real-time biochemical sensor based on Raman scattering with CMOS contact imaging.

This work presents a biochemical sensor based on Raman scattering with Complementary metal-oxide-semiconductor (CMOS) contact imaging. This biochemical optical sensor is designed for detecting the concentration of solutions. The system is built with a laser diode, an optical filter, a sample holder and a commercial CMOS sensor. The output of the system is analyzed by an image processing program. The system provides instant measurements with a resolution of 0.2 to 0.4 Mol. This low cost and easy-operated small scale system is useful in chemical, biomedical and environmental labs for quantitative bio-chemical concentration detection with results reported comparable to a highly cost commercial spectrometer.

A catheter-based acoustic interrogation device for monitoring motility dynamics of the lower esophageal sphincter.

This paper presents novel minimally-invasive, catheter-based acoustic interrogation device for monitoring motility dynamics of the lower esophageal sphincter (LES). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the sphincter to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be quantitatively assessed. In this paper, experiments are conducted utilizing an LES motility dynamics simulator. The sound strength is captured by the microphone and is correlated to the level of LES opening and closing controlled by the simulator. Measurements from the simulator model show statistically significant (p < 0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, D.O.F. = 9). Measuring the level of LES opening and closing has the potential to become a valuable diagnostic technique for understanding LES dysfunction and the disorders associated with it.

Transcutaneous intraluminal impedance measurement for minimally invasive monitoring of gastric motility: validation in acute canine models.

Transcutaneous intraluminal impedance measurement (TIIM) is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham), two force transducers (FT) were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs) were calculated and Pearson correlation coefficients (PCCs) between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans.

Performance quantification of a millimeter-wavelength imaging system based on inexpensive glow-discharge-detector focal-plane array.

Inexpensive millimeter-wavelength (MMW) optical digital imaging raises a challenge of evaluating the imaging performance and image quality because of the large electromagnetic wavelengths and pixel sensor sizes, which are 2 to 3 orders of magnitude larger than those of ordinary thermal or visual imaging systems, and also because of the noisiness of the inexpensive glow discharge detectors that compose the focal-plane array. This study quantifies the performances of this MMW imaging system. Its point-spread function and modulation transfer function were investigated. The experimental results and the analysis indicate that the image quality of this MMW imaging system is limited mostly by the noise, and the blur is dominated by the pixel sensor size. Therefore, the MMW image might be improved by oversampling, given that noise reduction is achieved. Demonstration of MMW image improvement through oversampling is presented.

Suture marker lesion detection in the colon by self-stabilizing and unmodified capsule endoscopes: pilot study in acute canine models.

BACKGROUND: Capsule endoscopy is a noninvasive method for examining the small intestine. Recently, this method has been used to visualize the colon. However, the capsule often tumbles in the wider colon lumen, resulting in potentially missed pathology. In addition, the capsule does not have the ability to distend collapsed segments of the organ. Self-stabilizing capsule endoscopy is a new method of visualizing the colon without tumbling and with the ability to passively distend colon walls. OBJECTIVE: To quantitatively compare the detection rate of intraluminal suture marker lesions for colonoscopy by using a custom-modified, self-stabilizing capsule endoscope (SCE); an unmodified capsule endoscope (CE) of the same brand; and a standard colonoscope. DESIGN: Four mongrel dogs underwent laparotomy and the implantation of 5 to 8 suture markers to approximate colon lesions. Each dog had both capsule endoscopy and self-stabilizing capsule endoscopy, administered consecutively in random order. In each case, the capsule was inserted endoscopically into the proximal lumen of the colon followed by pharmacologically induced colon peristalsis to propel it distally through the colon. Blinded standard colonoscopy was performed by an experienced gastroenterologist after the capsule endoscopies. SETTING: Experimental study in a live canine model. SUBJECTS: Four dogs. INTERVENTION: Laparotomy, capsule endoscopy, colonoscopy. MAIN OUTCOME MEASUREMENTS: Comparison of the marker detection rate of the SCE to that of the unmodified MiroCam CE and a colonoscope. RESULTS: The average percentages of the marker detection rate for unmodified capsule endoscopy, self-stabilizing capsule endoscopy, and colonoscopy, respectively, were 31.1%, 86%, and 100% (P < .01), with both self-stabilizing capsule endoscopy and colonoscopy performing significantly better than the unmodified capsule endoscopy. LIMITATIONS: Acute canine model, suture markings poorly representative of epithelial polyps, limited number of animals. CONCLUSION: The proposed self-stabilizing capsule endoscope delivered a significant improvement in detection rates of colon suture markings when compared with the unmodified capsule endoscope.

Low-voltage 96 dB snapshot CMOS image sensor with 4.5 nW power dissipation per pixel.

Modern "smart" CMOS sensors have penetrated into various applications, such as surveillance systems, bio-medical applications, digital cameras, cellular phones and many others. Reducing the power of these sensors continuously challenges designers. In this paper, a low power global shutter CMOS image sensor with Wide Dynamic Range (WDR) ability is presented. This sensor features several power reduction techniques, including a dual voltage supply, a selective power down, transistors with different threshold voltages, a non-rationed logic, and a low voltage static memory. A combination of all these approaches has enabled the design of the low voltage "smart" image sensor, which is capable of reaching a remarkable dynamic range, while consuming very low power. The proposed power-saving solutions have allowed the maintenance of the standard architecture of the sensor, reducing both the time and the cost of the design. In order to maintain the image quality, a relation between the sensor performance and power has been analyzed and a mathematical model, describing the sensor Signal to Noise Ratio (SNR) and Dynamic Range (DR) as a function of the power supplies, is proposed. The described sensor was implemented in a 0.18 um CMOS process and successfully tested in the laboratory. An SNR of 48 dB and DR of 96 dB were achieved with a power dissipation of 4.5 nW per pixel.

Quaternion structural similarity: a new quality index for color images.

One of the most important issues for researchers developing image processing algorithms is image quality. Methodical quality evaluation, by showing images to several human observers, is slow, expensive, and highly subjective. On the other hand, a visual quality matrix (VQM) is a fast, cheap, and objective tool for evaluating image quality. Although most VQMs are good in predicting the quality of an image degraded by a single degradation, they poorly perform for a combination of two degradations. An example for such degradation is the color crosstalk (CTK) effect, which introduces blur with desaturation. CTK is expected to become a bigger issue in image quality as the industry moves toward smaller sensors. In this paper, we will develop a VQM that will be able to better evaluate the quality of an image degraded by a combined blur/desaturation degradation and perform as well as other VQMs on single degradations such as blur, compression, and noise. We show why standard scalar techniques are insufficient to measure a combined blur/desaturation degradation and explain why a vectorial approach is better suited. We introduce quaternion image processing (QIP), which is a true vectorial approach and has many uses in the fields of physics and engineering. Our new VQM is a vectorial expansion of structure similarity using QIP, which gave it its name-Quaternion Structural SIMilarity (QSSIM). We built a new database of a combined blur/desaturation degradation and conducted a quality survey with human subjects. An extensive comparison between QSSIM and other VQMs on several image quality databases-including our new database-shows the superiority of this new approach in predicting visual quality of color images.

Self-stabilizing colonic capsule endoscopy: pilot study of acute canine models.

Video capsule endoscopy (VCE) is a noninvasive method for examining the gastrointestinal tract which has been successful in small intestine studies. Recently, VCE has been attempted in the colon. However, the capsule often tumbles in the wider colonic lumen, resulting in missed regions. Self-stabilizing VCE is a novel method to visualize the colon without tumbling. The aim of the present study was to comparatively quantify the effect of stabilization of a commercially available nonmodified capsule endoscope (CE) MiroCam and its modified self-stabilizing version in acute canine experiments. Two customized MiroCam CEs were reduced in volume at the nonimaging back-end to allow the attachment of a self-expanding, biocompatible stabilizing device. Four mongrel dogs underwent laparotomy and exteriorization of a 15-cm segment of the proximal descending colon. A single CE, either self-stabilizing or nonmodified was inserted through an incision into the lumen of the colon followed by pharmacologically induced colonic peristalsis. The inserted capsule was propelled distally through the colon and expelled naturally through the anus. Novel signal processing method was developed to quantify the video stabilization based on camera tracking a predetermined target point (locale). The average locale trajectory, the average radius movement of the locale, and the maximum rate of change of the locale for sequential images were significantly lower for the stabilized capsules compared to the nonstabilized ones . The feasibility of self-stabilized capsule endoscopy has been demonstrated in acute canine experiments.

Crosstalk quantification, analysis, and trends in CMOS image sensors.

Pixel crosstalk (CTK) consists of three components, optical CTK (OCTK), electrical CTK (ECTK), and spectral CTK (SCTK). The CTK has been classified into two groups: pixel-architecture dependent and pixel-architecture independent. The pixel-architecture-dependent CTK (PADC) consists of the sum of two CTK components, i.e., the OCTK and the ECTK. This work presents a short summary of a large variety of methods for PADC reduction. Following that, this work suggests a clear quantifiable definition of PADC. Three complementary metal-oxide-semiconductor (CMOS) image sensors based on different technologies were empirically measured, using a unique scanning technology, the S-cube. The PADC is analyzed, and technology trends are shown.

Low light CMOS contact imager with an integrated poly-acrylic emission filter for fluorescence detection.

This study presents the fabrication of a low cost poly-acrylic acid (PAA) based emission filter integrated with a low light CMOS contact imager for fluorescence detection. The process involves the use of PAA as an adhesive for the emission filter. The poly-acrylic solution was chosen due its optical transparent properties, adhesive properties, miscibility with polar protic solvents and most importantly its bio-compatibility with a biological environment. The emission filter, also known as an absorption filter, involves dissolving an absorbing specimen in a polar protic solvent and mixing it with the PAA to uniformly bond the absorbing specimen and harden the filter. The PAA is optically transparent in solid form and therefore does not contribute to the absorbance of light in the visible spectrum. Many combinations of absorbing specimen and polar protic solvents can be derived, yielding different filter characteristics in different parts of the spectrum. We report a specific combination as a first example of implementation of our technology. The filter reported has excitation in the green spectrum and emission in the red spectrum, utilizing the increased quantum efficiency of the photo sensitive sensor array. The thickness of the filter (20 µm) was chosen by calculating the desired SNR using Beer-Lambert's law for liquids, Quantum Yield of the fluorophore and the Quantum Efficiency of the sensor array. The filters promising characteristics make it suitable for low light fluorescence detection. The filter was integrated with a fully functional low noise, low light CMOS contact imager and experimental results using fluorescence polystyrene micro-spheres are presented.

Pilot study of temporary controllable gastric pseudobezoars for dynamic non-invasive gastric volume reduction.

Invasive surgical procedures for gastric volume reduction or bypass have been considered the most effective approach to sustainable long-term weight reduction. However, non-invasive techniques for dynamic volume reduction from inside the stomach are lacking. The aim of this study was to propose temporary, permeable, controllable pseudobezoars for non-invasive, long-term sustainable gastric volume reduction and to test them in pilot human studies. Permeable sac-like carriers made from biocompatible and biodegradable material were filled with expandable superabsorbent fiber and polymer granules. The implements were designed to prevent the expulsion of the pseudobezoars through the pylorus for a controlled time period. The pseudobezoars were administered transorally to two human patients (2M, 78.9 kg/174 cm, girth 88.1 cm, and 89.7 kg/175, girth 95.2 cm). Body weight dynamics, girth, level of satiety, stools, bowel regularity and notable side effects were monitored in three distinct 1 month periods: baseline, therapy and washout. Sonographic verification of the presence of pseudobezoars in the stomachs of both subjects was performed at the end of the therapy month and was repeated at the end of the washout period to examine the clearance of the implements. During the therapy month, both individuals exhibited significant weight and girth reduction (p < 0.05), and substantially increased satiety levels. The patients retained their bowel regularity and did not report any notable side effects. The temporary pseudobezoars were clearly noticeable sonographically in both patients at the end of the therapy month and cleared after its discontinuation. Controllable temporary pseudobezoars were designed and tested in pilot studies.

Efficient Biologically-based Pattern-recognizing Networks.

A biologiclly-motivated classifying neural network which is based on the feature extraction scheme found in the visual cortex is suggested. A special process is proposed for grading and automatically selecting the "best" features for specific recognition tasks. Ranking is based on a feature's calculated discriminating ability, such that a given class is separated from each and every other class by a given amount. The outcome is a net with less computational complexity than other neural nets, yet one which is more biologically plausible.The main motivation for constructing a reduced net is that the complex circuitry of the brain deals with a huge number of patterns, while a machine-based recognition system usually deals with a limited number of patterns. Results show that feature reduction is drastic and that very compact nets, of the order of tens of neurons, can be used to classify patterns, even in a noisy environment. Copyright 1996 Elsevier Science Ltd