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Colorimetric assays are an important tool in point-of-care testing that offers several advantages such as rapid response times and inexpensive costs. A factor that currently limits their use is objective measures to determine results. Current solutions consist of creating a test reader that standardizes the conditions the strip is under before measuring. However, this increases the cost and decreases the portability of these assays. The focus of this study is to train a convolutional neural network (CNN) that can objectively determine results of colorimetric assays under varying conditions. To ensure the flexibility of the model to several types of colorimetric assays, three models are trained on the same CNN. The images these models are trained on consist of positive and negative images of ETG (99.87% positive classification, 99.96% negative classification), fentanyl (99.60% positive classification, 99.56% negative classification), and HPV antibody (99.86% positive classification, 100% negative classification) strips taken under different lighting and background conditions. A fourth model is trained on an image set composed of all three strip types with the lowest classification accuracy being 99.11%.

The application of microfluidics in Point of Care (PoC) testing was a breakthrough in PoC diagnostics, yet high precision testing remains a challenge. In order to extract and isolate pure RNA or DNA from biofluids containing a virus or virion, small spherical magnetic particles called magnetic beads are commonly used in laboratories. Magnetic beads have many applications ranging from purification of nucleic acids, magnetic cell separation, targeted drug delivery to brain or malignant tumors, magnetic chaining etc. Unfortunately, integrating magnetic beads into PoC devices is challenging. This paper delves into a comparative study of the behaviour and parameters of five different sizes of carboxyl coated paramagnetic beads along with silica coated dynabeads. Their behavior is characterized in a microcapillary channel for a SARS-CoV-2 virus PoC testing kit to enrich the sample, concentrating the nucleic acid. This step would increase the sensitivity and specificity for any nucleic acid-based PoC testing device.

Ammonium nitrate and nitromethane are two of the most prevalent ingredients in improvised explosive devices (IED). Developing a detection system for IEDs in open public events where no specific check points are available requires many large scale, fine-grained simulations to estimate the explosive vapors. However, such large scale molecular simulations at the required granularity is very time consuming and in most cases not feasible. In this paper, we propose region-specific meshing to alleviate the computational cost. The proposed simulation methodology provides accurate results as compared with a baseline simulation of fine grained mesh (in a small area) while providing significant reduction in simulation time. Thus, large scale simulations at feasible computational burden can be achieved.

Thin-film microelectrode arrays have a wide variety of applications in research and medical devices. Conventionally, these arrays are fabricated through the use of photolithography, which can be problematic for innovative medical device fabrication due to long process times, inflexibility to design changes, and the reliance on potentially harmful chemicals. Here, we present the use of laser micromachining as an alternative to photolithography processes to fabricate thin-film polyimide microelectrode arrays. This fabrication method lends itself to an iterative design process as it can reduce fabrication steps and is attractive for medical devices since it can be used without harmful chemicals. Several process parameters were explored and the performance of the fabricated electrodes was compared to similar electrodes that were fabricated with conventional photolithography processes.

Point-of-care (PoC) testing systems aim to bring affordable and convenient diagnostics to resource limited locations. In our previous work in detecting human papilloma virus (HPV) via lateral flow immunoassays and fluorescence detection, we determined that the performance of the assay depends on the temperature and humidity. Thus, we need to maintain a fixed environment for the assay to produce reliable results. Therefore, we define the need for a portable, climate-controlled chamber for field work in low resource settings. By combining low-cost electronics and household items, a simple feedback loop is designed to regulate the internal conditions of the testing environment. The ability of our chamber to maintain a desired climate will be tested for accuracy and stability to ensure that it is competent for in-field usage.

We present a novel 3D printed Microfluidic Actuation System for lateral flow assay in low resource settings. The system is used to deliver reagents for multi-step assays from blisters placed into cavities in the 3D printed assembly. The system is operated by manually depressing the blister housing and rotating to the next blister location. This is repeated for each step in the assay to enable a simple and repeatable method of delivering specified volumes to the assay at arbitrary time intervals as required by the assay. The blisters provide for robust storage while maintaining consistent aliquots for the assay. We characterize the percent of the total volume delivered to the lateral flow assay from the blisters including the volume dispensed at given time intervals.

We previously reported a fluorescence-based Point-of-care (PoC) diagnostic for human papillomavirus (HPV). In this work, we present our progress in modifying the system for colorimetric testing. This decreases the number of steps required to complete the assay, simplifies calibration, and decreases the cost of the system. We were able to confirm the system was successfully modified for colorimetric detection using a newly designed 3D printed cartridge and calibration slides.

Lateral Flow Immunoassays (LFIAs) are among the most successful Point of Care (POC) tests. However, factors like reagent stability, reaction rates, and binding kinetics limit the performance and robustness of LFIAs. One of the factors that affects the overall performance of LFIA is the fluid flow rate, and hence, it is desirable to maintain a predictable fluid velocity in porous media. The main objective of this study is to build a statistical model that estimates the fluid velocity in porous media for any given ambient condition to enable us to determine the optimal design parameters for achieving a desired fluid velocity in porous media.

In this work, we offer a high level view of the difference in performance of three circuit architectures for estimating slowly changing current: the transimpedance amplifier, linear integrator, and integrate and fire. When considering a portable or IoT (Internet of Things) using a microprocessor-based system, we determine architecture trade-offs in performance fo a low-cost implementation. Given the constraints and capabilities of available microprocessor technologies, we provide a comparative analysis of the different architectures’ strengths and weaknesses.

While Volatile Organic Compounds (VOC) and ammonia have a place in our daily lives, their leakage into the environment is harmful to human health. In order to prevent and detect gaseous leaks of harmful VOCs, a cyber-physical system (CPS) comprised of ordinary people or first responders is proposed. This CPS uses small, low-cost sensors coupled to smart phones or mobile devices with the necessary computation and communication capabilities. The efficacy of such a CPS hinges on its ability to address technical challenges stemming from the fact that identically produced sensors may produce different results under the same conditions due to sensor drift, noise, or resolution errors.The proposed system makes use of time-varying signals produced by sensors to detect gas leaks. Sensors sample the gas vapor level in a continuous manner and time-varying sensor data is processed using deep neural networks. One of the neural networks (NN) is an energy efficient Additive Neural Network (AddNet) which can be implemented in host devices. The second NN is the discriminator of a GAN and the third a regular convolutional NN. AddNet produces comparable VOC gas leak detection results to regular convolutional networks while reducing area requirements by two thirds.

This paper presents a new concept combining flexible organic light-emitting diode (OLED) display technology with fluorescent biorecognition microarray technology to fabricate point-of-care immunobiosensors. Our approach is designed to leverage commercial OLED display technology to reduce pre-functionalized biosensor substrate costs to pennies per ${cm}^{2}$ combined with leveraging the display industries ability to manufacture an immense number of low-cost consumer electronic products annually. For this work, we demonstrate that our new approach using high brightness flexible OLED display technology combined with a charge integrating readout circuit and optical filters can offer point-of-care diagnostic sensitivity at or below 10 pg/mL, which approaches the lower limit of detection (LLOD) of typical clinical laboratory instrumentation.

We present a low-cost fluorescence and colorimetry label detection platform for point-of-care (POC) applications. Our platform is designed to deliver clinical level diagnostic sensitivity. It improves the performance of the traditional lateral flow assay (LFA) by decreasing the detection limit by 3 orders of magnitude and enabling quantitative detection of analytes. In this work, we characterize the fluorescence detection platform and detail the effects of label selection on the overall system performance. The effects of optoelectronic configuration, brightness, and spectral matching are presented. Finally, we demonstrate the utility of our platform for colorimetric detection and compare its performance to a standard central laboratory microplate reader. The limit-of-detection (LOD) for our point-of-care platform was determined to be the same as the microplate reader, detecting 2 × 104 0.5 µm microspheres without the use of focusing or transfer optics.

Stimulation has been a key technique for studying underlying mechanisms of the nervous system. Electrical stimulation has been the predominant method for eliciting desired muscle responses for decades, yet methodologies remain invasive and low in selectivity of tissue stimulated. Current injection affects all local tissue types and can lead to damaging immune responses that threaten both nerves and equipment alike. Optogenetics provides a solution for such stimulation difficulties by increasing specificity and decreasing risk to tissue. Via genetic modifications, opsins (light-sensitive proteins) are added to neurons, and can be activated by light to cause neuron excitation. Through preliminary in vivo testing in transgenic mice expressing channelrhodopsin (ChR2) we validate that multiple beams of light have an additive effect and increase the response from muscles innervated by the target nerve. Measuring hindlimb flexion increases with increase in number of light sources present. To further characterize this additive effect, a Monte Carlo computer model was generated to simulate a random-walk of photons passing through nerve tissue. The model shows that light beams can aggregate within the nerve, although are limited. When using collimated light, multiple beams converging on the interior region of the nerve cannot result in a higher intensity than outermost layer of tissue nearest a single light source. This model serves as a tool to aid future animal studies by determining light emission parameters, specifically prescribing the need for optically-focused light, when attempting to selectively stimulate regions deep in the interior of a given nerve. Such capability will allow for high spatial resolution of stimulation in peripheral nerves giving finer control of excitation in downstream tissue.

The growing market for wearable, portable, and IoT devices has generated a need for a class of circuits to meet the requirements for these applications. In this work we specifically investigate ammeters. The design space requires low component count circuits for measuring slowly varying currents using low-cost microcontrollers. Simple architectures, feasible for an electronics novice are described and compared experimentally. The use of the time domain to improve error and range of measurement is considered. This guide provides an individual without extensive electronics design experience with a simple selection guide for choosing the appropriate architecture for their specific application.

Point-of-care medical diagnostics can provide efficient, cost-effective medical care, and have the potential to fundamentally change our current approach to global health. There have been substantial efforts in developing lateral flow assays for serologic testing, but most of the existing approaches have limited portability, are expensive, and offer limited analytical sensitivity. In this paper, we demonstrated an assay for the detection of antibodies in plasma to Epstein-Barr Nuclear Antigen-1 (EBNA-1) protein and optimization of the assay including washing and blocking conditions. We also investigated the effect of the storage on the assay strips. Using our optimized conditions, we were able to detect anti-Human Papilloma Virus (HPV)-16 E7 antibodies after three weeks of storage. Our goal is to adapt this system to detect HPV biomarkers for cervical cancers in low and middle-income countries.

Fluorescence- based lateral flow immunoassays (LFIAs) remain relatively unexplored compared to colorimetric LFIAs for point-of-care (PoC) disease diagnosis and health monitoring. For fluorescence-based LFIAs, a major challenge includes the auto-fluorescence of the nitrocellulose and nonspecific binding of fluorescent polystyrene microspheres. In this paper, we aim to characterize antibody-microsphere conjugates in a fluorescence-based serological assay on nitrocellulose. Factors such as coating concentration and quantity of microspheres were considered and their impacts on nonspecific binding and signal-to-noise ratio are discussed. Finally, we use the determined conditions for the antibody-microsphere conjugates to demonstrate the sensitivity of a proof-of-concept assay detecting antibodies to Epstein-Barr Nuclear Antigen-1 in pooled human plasma samples. A titration of the seropositive plasma samples demonstrated a titer approaching 1:1,000 using only 30 μL of diluted sample and a sample-to-result time of less than one hour.

Arizona State University (ASU) established an NSF Research Experiences for Undergraduates (REU) site to embed students in research projects related to integrated sensor and signal processing systems. The program includes both sensor hardware and algorithm/software design for a variety of applications including health monitoring. The site was funded in February 2017 and the Co-PIs recruited nine students from different universities and community colleges to spend the summer of 2017 in research laboratories at ASU. The program included structured training with modules in sensor design, signal processing, and machine learning. Cross-cutting training included research ethics, IEEE manuscript development, and building presentation skills. Nine undergraduate research projects were launched and the program went through an assessment by an independent evaluator. This paper describes the REU activities, modules, training, projects, and their assessment.

The work presents implementing a low cost pH sensing system for biological applications in a flexible electronics process. As a part of the system the work describes an ion sensitive field effect transistor, using indium tin oxide (ITO) as a sensing layer and gold as a reference electrode, on a flexible substrate. The devices presented here are designed and fabricated using the thin film transistor (TFT) display technology at the Arizona State University Flexible Electronics and Display Center. It was observed that ITO has a sensitivity of 50 mV/pH. The work also discusses the variability in these devices and signal processing that could be used to calibrate them. Toward this end, a readout circuit designed in a 0.5 μm CMOS process is presented to interface with the sensors.

This paper demonstrates a self-powered Maximum Power Direction Tracking (MPDT) system capable of maximizing the energy harvesting by automatically adjusting the angle of the solar panel. The whole system is powered by a solar panel so no extra power supply is needed. The entire system consists of a solar panel, a motor, and a CMOS chip. A novel light direction sensor and the needed circuit are integrated in a single chip which is fabricated by a standard 0.5 μm CMOS process. So it is small-size and low-cost. The system was tested to verify performance with different light direction and intensity. The results show that the system has good sensitivity to the incident angle and achieve tracking accuracy of ± 1.8 ° over a optical power range of 30–110 mW / cm 2 . The presented system obtains an average output power gain of 18.4% over the fixed southwards mounted system under real weather conditions.

Point-of-Care (PoC) diagnostic devices, such as lateral flow tests, are often used in low and middle-income countries (LMIC) for low-cost disease detection. Most commercial lateral flow tests use colorimetric detection on a nitrocellulose substrate. In this paper, we present a multistep, fluorescence-based assay detection system, which can detect antibodies in plasma to recombinant protein. Fluorescence-based detection allows us to achieve higher sensitivity, while a nitrocellulose substrate enables fluid handling, high protein immobilization, rapid detection time, and affordability. As a proof-of-concept for detection of disease-specific biomarkers in plasma, we demonstrate the detection of antibodies in plasma to Epstein-Barr nuclear antigen-1 (EBNA-1) recombinant protein and to human papillomavirus (HPV) 16 E7 recombinant protein. We show that our detection system is able to detect EBNA-1-specific antibodies at a 1:10,000 plasma dilution and HPV 16 E7-specific antibodies at a 1:5,000 plasma dilution, indicating high sensitivity. This platform is a low-cost device that can detect fluorescence from labeled biomarkers on a lateral flow assay. Ultimately, we aim to adapt this system to detect HPV 16 and 18 biomarkers for cervical cancer screening in LMICs.

In this work, we demonstrate the alpha prototype for a wearable air quality sensor system. This system will be used to create precise, high-resolution maps of the environment to help individuals with respiratory disease track their response to pollutants, determine when to pre-medicate, or avoid areas with poor air quality altogether. The data from such a map will provide improved accuracy over the single air quality index value provided for large metropolitan areas. We provide data from continuous monitoring over several locations to demonstrate the difference that can be observed within a small geographic area.

Childhood asthma has effectively doubled since 1980 and currently affects about 8% of the U.S. childhood population. Efficiently analyzing quality of air data, which would ultimately improve the information available to parents with children suffering from asthma, is crucial to reduce the likelihood of a serious attack. In order to accomplish this task, the use of low-cost, wearable, environmental sensors contribute to construct a live “air-care” pollution map. Creating an alpha prototype application to gauge how well participants interact with and interpret healthcare information utilizing a “Wizard of Oz” paradigm becomes an important component in the research.

This paper provides a solution for a self-powered light direction detection with digitized output. Light direction sensors, energy harvesting photodiodes, real-time adaptive tracking digital output unit and other necessary circuits are integrated on a single chip based on a standard 0.18 µm CMOS process. Light direction sensors proposed have an accuracy of 1.8 degree over a 120 degree range. In order to improve the accuracy, a compensation circuit is presented for photodiodes' forward currents. The actual measurement precision of output is approximately 7 ENOB. Besides that, an adaptive under voltage protection circuit is designed for variable supply power which may undulate with temperature and process.

We demonstrate a minimally invasive intracranial pressure (ICP) monitoring system using a piezoresistive sensor. Our previous work in ICP monitoring used an obscure sensor, small pressure range, and manual induction by hand compressions. In this work, we use a widely available FDA-approved sensor and extend the study to meet the ANSI/AAMI standards. We also include controlled mechanical and physiologically-induced ICP modulation. We verified the system using a water column up to 100 mmHg. We tested our system in vivo with a rat model. The results generally show excellent agreement between our custom ICP sensing system and a commercial gold standard.

An effective method of combating infectious diseases is the deployment of hand-held devices at the point-of-care (POC) for screening or self-monitoring applications. There is a need for very sensitive, low-cost and quantitative diagnostic devices. In this study, we present a low-cost, multiplexed fluorescence detection platform that has a high sensitivity and wide dynamic range. Our system features inexpensive 3 × 3 mm interference filters with a high stopband rejection, sharp transition edges, and greater than 90% transmission in the passband. In addition to the filters, we improve signal-to-noise ratio by leveraging time for accuracy using a charge-integration-based readout. The fluorescence sensing platform provides a sensitivity to photon flux of ∼ 1 × 10 4 photons / mm 2 sec and has the potential for 2–3 orders of magnitude improvement in sensitivity over standard colorimetric detection that uses colored latex microspheres. We also detail the design, development, and characterization of our low-cost fluorescence detection platform and demonstrate 100% and 97.96% reduction in crosstalk probability and filter cost, respectively. This is achieved by reducing filter dimensions and ensuring appropriate channel isolation in a 2 × 2 array configuration. Practical considerations with low-cost interference filter system design, analysis, and system performance are also discussed. The performance of our platform is compared to that of a standard laboratory array scanner. We also demonstrate the detection of antibodies to human papillomavirus (HPV16) E7 protein, as a potential biomarker for early cervical cancer detection in human plasma.

This Live Demonstration shows a compact, low-cost, disposable fluorescence detection platform, using an LFA test strip or sample cartridge, with up to a 1000-fold enhancement in sensitivity over visual colorimetric readouts. The system achieves a high sensitivity by combining low-cost discrete electronic components with optical interference filters. A sample measurement takes less than a minuite, trading time for accuracy by using a charge integration amplifier. This system is capable of detecting HPV in human sera with a sensitivity of 10 pg/mL [1].

ObjectiveThere is a need for low power, scalable photoelectronic devices and systems for emerging optogenetic needs in neuromodulation. Conventional light emitting diodes (LEDs) are constrained by power and lead-counts necessary for scalability. Organic LEDs (OLEDs) offer an exciting approach to decrease power and lead-counts while achieving high channel counts on thin, flexible substrates that conform to brain surfaces or peripheral neuronal fibers. In this study, we investigate the potential for using OLEDs to modulate neuronal networks cultured in vitro on a transparent microelectrode array (MEA) and subsequently validate neurostimulation in vivo in a transgenic mouse model.ApproachCultured mouse cortical neurons were transfected with light-sensitive opsins such as blue-light sensitive channel-rhodopsin (ChR2) and green-light sensitive chimeric channel-rhodopsin (C1V1tt) and stimulated using blue and green OLEDs (with 455 and 520 nm peak emission spectra respectively) at a power of 1 mW/mm2 under pulsed conditions.Main resultsWe demonstrate neuromodulation and optostimulus-locked, single unit-neuronal activity in neurons expressing stimulating and inhibiting opsins (n=4 MEAs, each with 16 recordable channels). We also validated the optostimulus-locked response in a channel-rhodopsin expressing transgenic mouse model, where at least three isolatable single neuronal cortical units respond to OLED stimulation.SignificanceThe above results indicate the feasibility of generating sufficient luminance from OLEDs to perform neuromodulation both in vitro and in vivo. This opens up the possibility of developing thin, flexible OLED films with multiple stimulation sites that can conform to the shape of the neuronal targets in the brain or the peripheral nervous system. However, stability of these OLEDs under chronic conditions still needs to be carefully assessed with appropriate packaging approaches.

This paper presents a new biophotonic application for large-area, high-resolution, flexible organic light-emitting diode (OLED) display technology currently used to manufacture low-cost color flexible displays on plastic substrates. The new concept uses a fully addressable high resolution flexible OLED pixel array on a thin, mechanically compliant biocompatible plastic substrate to selectively stimulate and/or silence small groups of neurons on either the cortical surface or, alternatively, within the deep brain. Optical measurements from a 455 nm blue flexible OLED test structure demonstrated the ability to emit 1 ${\hbox{mW/mm}}^{2}$ of instantaneous light intensity using a 13 V, 20 Hz pulse, which meets the minimum reported intensity at $\sim$ 450 nm to induce optical stimulation in genetically modified neural tissue. Biocompatibility was successfully demonstrated by the ability to grow human epithelial cells on the surface of a full TFT process flow plastic flexible display substrate. Additionally, a new active matrix array display architecture was designed to support pulsed mode OLED operation. These preliminary results demonstrate the initial viability of extending flexible plastic substrate OLED display technology to the development of large-area, high-resolution emissive active matrix arrays for chronic optogenetic applications.

In this work we present a system designed for continuous assessment of tumor cell extracellular pH using a fabricated quartz extended-gate ion-sensitive field effect transistor (EGFET). The extended gate structure was fabricated by patterning gold on a quartz substrate creating a pseudo-reference electrode and sensor below a Si 3 N 4 sensing membrane. Various electrode geometries and configurations were created and each pattern was characterized. A readout/data acquisition system was designed to convert the current output of the EGFET to a voltage that was recorded using a low-power single board computer, which performed a hard "reset" before every data acquisition interval. This setup was able to monitor the viability of SKBR3 mammary gland tumor cells treated with staurosporine. Over a span of 8 hours, the autonomous data acquisition system recorded a steady decrease in cell viability. Results were verified with periodic cell culture images. Future applications include design of an extended gate EGFET array, which allows for accurate monitoring of individual cell cultures.

The high per patient cost of quantitative, high-sensitivity molecular diagnostics is one of the key roadblocks limiting the transition of this technology from the clinical laboratory to point-of-care diagnostics in low-to-middle income countries (LMICs). As a solution, we present a low-cost system architecture for fluorescence-based point-of-care diagnostics using small volume patient sera samples. Our approach combines an inexpensive 4-site microscope slide reader with low per patient cost consumables using conventional glass microscope slides, pre-printed with biorecognition molecules. We use a neuromorphic-inspired, charge-integrating readout circuit architecture combined with optical filters in a sandwich-style configuration to achieve high-sensitivity while trading off detection time and number of biorecognition sites per slide. Our demonstrated lower limit of detection using Nile Red fluorescent microspheres was a 1,000,000:1 dilution corresponding to approximately 200 microspheres per detection site, approaching the sensitivity of a conventional high-cost desktop clinical laboratory microscope slide reader.

This work details the design and characterization of a low-cost, portable and highly sensitive fluorescence detection system intended for use in a compact and disposable point-of-care (POC) device. The detection device leverages time integration to improve the signal to noise ratio (SNR) compared to instantaneous measurements. It also eliminates complicated focusing optics and electronics typically found in bulky and expensive laboratory-scale devices. Characterization was performed by measuring a series of logarithmically scaled dilutions of 1 μm Nile Red fluorescent microspheres immobilized on microscope slides. This approach eliminates assay dependencies and elucidates the actual system performance. A theoretical model that predicts the time-integrated output voltage profile of the sensor was developed; this prediction is useful for evaluating any lens-free fluorescent system based on a set of filters and choice of fluorophore. By relating the fluorophore concentration, system design parameters, and the output voltage, the model matches well with the empirical data and the limit of determination (LOD) for Nile Red is 20 particles. This system provides a sensitive and potentially low-cost device for fluorescent diagnosis in an integrated and compact/miniaturized POC device, lab-on-chip or a table-top reader.

One of the most life-threatening neural conditions is elevated intracranial pressure (ICP); it is associated with ischemia and poor short- and long-term outcomes. Currently, monitoring systems that accurately measure ICP are either highly invasive or inaccurate. This work explores the design and evaluation of an epidural intracranial pressure monitoring system for low-cost, minimally invasive detection. Our goal is to develop a monitoring system that could also be integrated with an electrocorticography (ECoG) system. To this end we created a minimally invasive epidural ICP monitor for use with a 2 mm burr hole craniotomy. A MEMS piezoresistive sensors is used in the system, and its performance is evaluated for intracranial pressure measurements. Our system is calibrated and tested on the benchtop and demonstrated in vivo using an animal model.

Point-of-care molecular diagnostics can provide efficient and cost-effective medical care and they have the potential to fundamentally change our approach to global health. However, most existing approaches are not scalable to include multiple biomarkers. As a solution, we have combined commercial flat panel OLED display technology with protein microarray technology to enable high-density fluorescent, programmable, multiplexed biorecognition in a compact and disposable configuration with clinical-level sensitivity. Our approach leverages advances in commercial display technology to reduce pre-functionalized biosensor substrate costs to pennies per cm2. Here, we demonstrate quantitative detection of IgG antibodies to multiple viral antigens in patient serum samples with detection limits for human IgG in the 10 pg/mL range. We also demonstrate multiplexed detection of antibodies to the HPV16 proteins E2, E6 and E7, which are circulating biomarkers for cervical as well as head and neck cancers.

PURPOSE Sweat is a relatively unexplored biofluid for diagnosis and monitoring of disease states. In this study, the proteomic profiling of immune-related biomarkers from healthy individuals are presented. EXPERIMENTAL DESIGN Eccrine sweat samples are collected from 50 healthy individuals. LC-MS/MS is performed on two pools of sweat samples from five male and female participants. Individual sweat samples are analyzed by antibody isotyping microarrays (n = 49), human cytokine arrays (n = 30), and quantitative ELISAs for interleukin-1α (n = 16), epidermal growth factor (n = 6), and angiogenin (n = 7). RESULTS In sweat, 220 unique proteins are identified by shotgun analysis. Detectable antibody isotypes include IgA (100% positive; median 1230 ± 28 700 pg mL-1 ), IgD (18%; 22.0 ± 119 pg mL-1 ), IgG1 (96%; 1640 ± 6750 pg mL-1 ), IgG2 (37%; 292 ± 6810 pg mL-1 ), IgG3 (71%; 74.0 ± 119 pg mL-1 ), IgG4 (69%; 43.0 ± 42.0 pg mL-1 ), and IgM (41%; 69.0 ± 1630 pg mL-1 ). Of 42 cytokines, three are readily detected in all sweat samples (p

This paper described a novel physiologically compatible wafer bonding technique for bio-microelectromechanical systems (bio-MEMS) packaging. Room temperature bonding was performed between Parylene-C and silicon wafers with a thin Parylene-C coating using reactive Ni/Al nanofilms as localized heaters. Live NIH 3T3 mouse fibroblast cells were encapsulated in the package and they survived the bonding process owing to the localization of heating. A numerical model was developed to predict the temperature evolutions in the parylene layers, silicon wafer and the encapsulated liquid during the bonding process. The simulation results were in agreement with the cell encapsulation experiment revealing that localized heating occurred in this bonding approach. This study proved the feasibility of reactive nanofilm bonding technique for broad applications in packaging bio-MEMS and microfluidic systems.

Electrochemical Impedance Spectroscopy (EIS) is a label-free method of molecular detection of particular interest for biomedical applications. We aim to create a hand-held, easy to use EIS measurement device, for biomolecular detection. Electrochemical cyclic voltammetry systems help millions of diabetics monitor their blood glucose levels 2–8 times per day, but their use is very limited due to the poor lower limit of detection. The EIS technique can be used to detect a much larger array of biomolecules at very low concentration. Our EIS system generates the magnitude and phase of the impedance from test samples via MATLAB, which provides the real and imaginary components of the impedance. The circuit was integrated on a single chip and fabricated in a standard 0.5 μm CMOS technology. A hand-held EIS measurement system was built using the chip and an Arduino Uno to measure a Randles circuit equivalent over the frequency range from 1 Hz to 2 kHz, the measurement and simulation results show excellent agreement.

We demonstrate the cycling of electric fields within an ion-sensitive field-effect transistor (ISFET) as a method to control drift. ISFETs had a repeatable drift pattern when cycling the vertical electric field by changing the voltage between the reference electrode and the substrate. Cycling the horizontal electric field, the voltage between the drain and source of the device, showed no effect, causing the device to continue to drift as it would during normal operation. Results were confirmed with multiple pH buffer solutions. An ISFET was modeled using ATHENA. The simulation included the electrolyte modeled as a modified intrinsic semiconductor. Empirical results are confirmed with device-level simulations of an ISFET using Silvaco TCAD. The model produced a scaled current of 90 μA, which is of similar order to the experimental values of 146 μA. The repeatable drift behavior could be easily reconciled to permit the use of ISFETs for long-term continuous monitoring applications.

We presents an ion sensitive field effect transistor to measure the pH of the cell culture media of human mammary adenocarcinoma (SKBR3). We use a drift mitigation technique that cycles the transistor to reset the drift in the system. We use to technique in the system to demonstrate an integrated system to monitor the pH continuously. As a part of the system a pulse width modulation circuit is designed in a 0.5 μm CMOS process which cycles the vertical electric field of the ion sensitive field effect transistor to reset the threshold voltage drift. We demonstrate the viability of a complete integrated system implementing our drift mitigation technique to monitor cultured cells. The integration is important in this application to allow for autonomous operation inside an incubator during cell culture.

This paper presents a floating gate Ion Sensitive Field Effect Transistor (ISFET) to monitor the activity of breast cancer cells. We use an ISFET to monitor the change in pH of the cell culture media and to observe the apoptosis of the breast cancer cells when treated with staurosporine. Since ISFETs suffer from inherent mismatch and drift in the threshold voltage, predominantly caused due to accumulation of ions on the surface of the gate, we have integrated a floating gate ISFET to calibrate the device. Floating gate ISFETs have been used to program the threshold voltage of the device either by hot electron injection, Fowler-Nordheim tunneling, and UV to remove charges. In this work we use hot electron injection to precisely program the device and tunneling as a global erase. This enables us to precisely record the changes in pH. These floating gate devices have been fabricated in 0.5 μm CMOS process.

We demonstrate a microfluidic system which applies engineering feedback principles to control the pH of a solution with a high degree of precision. The system utilizes an extended-gate ion-sensitive field-effect transistor (ISFET) along with an integrated pseudo-reference electrode to monitor pH values within a microfluidic reaction chamber. The monitored reaction chamber has an approximate volume of 90 nL. The pH value is controlled by adjusting the flow through two input channels using a pulse-width modulated signal applied to on-chip integrated valves. We demonstrate real-time control of pH through the feedback-controlled stepping of 0.14 pH increments in both the increasing and decreasing direction. The system converges to the pH setpoint within approximately 20 seconds of a step change. The integration of feedback theory into a microfluidic environment is a necessary step for achieving complete control over the microenvironment.

We demonstrate a CMOS (complementary metal oxide semiconductor) potentiostat chip fabricated in a standard 0.5 μm CMOS process to perform electrochemical analysis via cyclic voltammetry. This chip contains six independent channels for three electrode systems in electrochemical cells. Our low power circuit has been designed to drive electrochemical reactions in solution using class AB folded cascode amplifiers. The circuit operates with rail to rail input and output and has strong drive ability. We have shown the potentiostat chip is capable of performing cyclic voltammetry (CV) with both potassium ferricyanide and hexaammineruthenium chloride solutions. The chip is capable of differentiating both the composition and concentration of the solution. We compare our results with control experiments on a Gamry commercial electrochemical workstation and demonstrate they are consistent.

We present an optical localization chip capable of detecting the direction of incident light. The chip requires no offchip optical or mechanical components or post-processing (e.g. baffles, slits, mirrors, etc.). The chip was fabricated in a standard 0.5 μm CMOS (complementary metal oxide semiconductor) process. Our approach employs 100 light sensing cells, each having two detectors separated by a metal “wall”. The “wall” was created by stacking all metal layers, contacts and vias available in the process. This metal stack “wall” is used to create on-chip shadowing to facilitate detection. Each optical detection element produces a differential output with the normalized difference between the currents dependent upon the angle of the incident light. The width of the photodiodes is limited by the height of the metal wall to only a few micrometers. To achieve a good sensitivity, 100 cells are placed in parallel. Test results show good sensitivity to the direction and intensity of the incident light with accuracy of 1.9 degrees over a 100 degree range and 1.1 degrees over a 50 degree range.

We present the simulation results for a Pulse Width Modulation (PWM) circuit (to be fabricated in a 0.5 μm CMOS process) used to cycle the electric field in an Ion Sensitive Field Effect Transistor (ISFET). Vertical electric field, which controls the inversion layer in a field effect transistors, can be used to reset the inherent drift behavior of ISFET. A PWM circuit, to cycle the vertical field, enables us to precisely monitor the pH of an electrolyte without needing to manually calibrate the ISFET. Two or more ISFETs could be used with the devices alternatively being placed in reset and measurement mode. By combining the outputs from measurement phase of the devices, we can read the pH of the electrolyte continuously. The PWM circuit is composed of a 10.9 kHz ring oscillator, five divider circuits giving a 100,000 frequency division, a 6 bit counter, and a Digital to Analog Converter (DAC) that feeds into a comparator whose output selects the mode of operation for the ISFETs.