Vamsy P. Chodavarapu

NeuroMEMS: Neural Probe Microtechnologies

Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimers, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultra-long multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

CMOS-Based Phase Fluorometric Oxygen Sensor System

The design and development of a phase fluorometric oxygen (O2 ) sensor system using single-chip CMOS detection and processing integrated circuit (DPIC) and sol-gel derived xerogel thin-film sensor elements is described. The sensor system determines analyte concentrations using the excited state lifetime measurements of an O2-sensitive luminophore (tris(4,7-diphenyl-1,10- phenathroline)ruthenium (II)) embedded in the xerogel matrix. A light emitting diode (LED) is used as the excitation source, and the fluorescence is detected by the DPIC using a 16times16 phototransistor array on-chip. The DPIC also consists of a current mirror, current-to-voltage converter, amplifier, bandpass filter, and phase detector. The DPIC output is a dc voltage that corresponds to the detected fluorescence phase shift. With a 14-kHz modulation frequency, the entire system including driving the LED consumes 80 mW of average power. The sensor system provides stable, reproducible, analytically reliable, and fast response (~20 s) to changes in the gaseous oxygen concentrations and establishes the viability for low cost, low power and miniaturized biochemical sensor systems

Colorimetric porous photonic bandgap sensors with integrated CMOS color detectors

In this paper, the development of a novel colorimetric sensor system based on the integration of complementary metal-oxide-semiconductor (CMOS) color detectors with a modified porous polymeric photonic bandgap sensor is reported. The color detector integrated circuit IC is implemented with AMI (AMI Semiconductor) 1.5 mum technology, a standard CMOS fabrication process available at MOSIS (http://www.mosis.org). The color detectors are based on the spectral responses of buried double junctions (BDjs) and stacked triple junctions (STJs); the ratio of the photocurrents at the junctions provides spectral information. Both types of color detectors are characterized with a monochromator, and the results are compared. The BDJ color detector is used with a porous photonic bandgap reflection grating whose reflection spectra shifts as a function of the concentration of vapor analyte present. The experimental results verify that the color change of the photonic crystal can be detected and correlated to the change in analyte concentration. The entire system is compact and low power

Bacteria Growth Monitoring Through a Differential CMOS Capacitive Sensor

In this paper, we present a bacteria growth monitoring technique using a complementary metal-oxide semiconductor capacitive sensor. The proposed platform features a differential capacitive readout architecture with two interdigitized reference and sensing electrodes. These electrodes are exposed to pure Luria-Bertani (LB) medium and Escherichia Coli (E. Coli) bacteria suspended in the LB medium, respectively. In order to direct the solutions toward the electrodes, two microfluidic channels are implemented atop the electrodes through a direct-write assembly technique. We thereafter demonstrate and discuss the experimental results by using two different bacteria concentrations in the order of 106 and 107 per 1 mL in the LB medium.

A Camera Phone Localised Surface Plasmon Biosensing Platform towards Low-Cost Label-Free Diagnostic Testing

Developmental work towards a camera phone diagnostic platform applying localized surface plasmon resonance (LSPR) label-free sensing is presented. The application of spherical gold nanoparticles and nanorods are considered and assessed against ease of application, sensitivity, and practicality for a sensor for the detection of CCL2 (chemokine ligand 2). The sensitivity of the platform is compared with that of a commercial UV/Vis spectrometer. The sensitivity of the camera phone platform is found to be 30% less than that of the commercial system for an equivalent incubation time, but approaches that of the commercial system as incubation time increases. This suggests that the application of LSPR sensing on a portable camera phone devices may be a highly effective label-free approach for point-of-care use as a low-cost diagnostic sensing tool in environments where dedicated equipment is not available.

CMOS Optoelectronic Lock-In Amplifier With Integrated Phototransistor Array

We describe the design and development of an optoelectronic lock-in amplifier (LIA) for optical sensing and spectroscopy applications. The prototype amplifier is fabricated using Taiwan Semiconductor Manufacturing Co. complementary metal-oxide semiconductor 0.35-μm technology and uses a phototransistor array (total active area is 400 μm × 640μm) to convert the incident optical signals into electrical currents. The photocurrents are then converted into voltage signals using a transimpedance amplifier for subsequent convenient signal processing by the LIA circuitry. The LIA is optimized to be operational at 20-kHz modulation frequency but is operational in the frequency range from 13 kHz to 25 kHz. The system is tested with a light-emitting diode (LED) as the light source. The noise and signal distortions are suppressed with filters and a phase-locked loop (PLL) implemented in the LIA. The output dc voltage of the LIA is proportional to the incident optical power. The minimum measured dynamic reserve and sensitivity are 1.31 dB and 34 mV/μW, respectively. The output versus input relationship has shown good linearity. The LIA consumes an average power of 12.79 mW with a 3.3-V dc power supply.

A Polypyrrole-based Strain Sensor Dedicated to Measure Bladder Volume in Patients with Urinary Dysfunction

This paper describes a new technique to measure urine volume in patients with urinary bladder dysfunction. Polypyrrole – an electronically conducting polymer - is chemically deposited on a highly elastic fabric. This fabric, when placed around a phantom bladder, produced a reproducible change in electrical resistance on stretching. The resistance response to stretching is linear in 20%-40% strain variation. This change in resistance is influenced by chemical fabrication conditions. We also demonstrate the dynamic mechanical testing of the patterned polypyrrole on fabric in order to show the feasibility of passive interrogation of the strain sensor for biomedical sensing applications.

CMOS Conductometric System for Growth Monitoring and Sensing of Bacteria

We present the design and implementation of a prototype complementary metal-oxide semiconductor (CMOS) conductometric integrated circuit (IC) for colony growth monitoring and specific sensing of Escherichia coli (E. coli) bacteria. The detection of E. coli is done by employing T4 bacteriophages as receptor organisms. The conductometric system operates by measuring the resistance of the test sample between the electrodes of a two-electrode electrochemical system (reference electrode and working electrode). The CMOS IC is fabricated in a TSMC 0.35-μm process and uses a current-to-frequency (I to F) conversion circuit to convert the test sample resistance into a digital output modulated in frequency. Pulsewidth control (one-shot circuit) is implemented on-chip to control the pulsewidth of the output digital signal. The novelty in the current work lies in the ability of the CMOS sensor system to monitor very low initial concentrations of bacteria (4×102 to 4×104 colony forming unit (CFU)/mL). The CMOS system is also used to record the interaction between E. coli and its specific receptor T4 bacteriophage. The prototype CMOS IC consumes an average power of 1.85 mW with a 3.3-V dc power supply.

Bacteria growth monitoring through an on-chip capacitive sensor

In this paper, a charge based capacitive biosensor is presented for bacteria growth monitoring (BGM). This sensor chip is implemented through CMOS process in order to show the applicability of the proposed on-chip capacitive technique for BGM purposes. The passivated interdigitated electrodes atop CMOS chip are exposed to Escherichia coli (Ecoli) bacteria in the channel. The presence of bacteria in proximity of electrode causes a minute change in double layer capacitance. The variation of this capacitance (DeltaC<60 pF) versus time is demonstrated and compared with conventional impedance-based technique.

Sensitivity-Enhanced CMOS Phase Luminometry System Using Xerogel-Based Sensors

We present the design and implementation of a phase luminometry sensor system with improved and tunable detection sensitivity achieved using a complementary metal-oxide semiconductor (CMOS) integrated circuit. We use sol-gel derived xerogel thin films as an immobilization media to house oxygen (O2) responsive luminescent molecules. The sensor operates on the principal of phase luminometry wherein a sinusoidal modulation signal is used to excite the luminophores encapsulated in the porous xerogel films and the corresponding phase shift of the emission signals is monitored. The phase shift is directly related to excited state lifetimes of the luminophores which in turn are related to the concentration of the target analyte species present in the vicinity of the luminophores. The CMOS IC, which consists of a 16 times 16 high-gain phototransistor array, current-to-voltage converter, amplifier and tunable phase shift detector, consumes an average power of 14 mW with 5-V power supply operating at a 38-kHz modulation frequency. The output of the IC is a dc voltage that corresponds to the detected luminescence phase shift with respect to the excitation signal. As a prototype, we demonstrate an oxygen sensor system by encapsulating the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) within the xerogel matrices. The sensor system showed a fast response on the order of few seconds and we obtained a detection sensitivity of 118 mV per 1% change in O2 concentration. The system demonstrates a novel concept to tune and improve the detection sensitivity for specific concentrations of the target analyte in many biomedical monitoring applications.