Jennifer Blain Christen

Design, Fabrication, and Testing of a Hybrid CMOS/PDMS Microsystem for Cell Culture and Incubation

We discuss the design, fabrication, and testing of a hybrid microsystem for stand-alone cell culture and incubation. The micro-incubator is engineered through the integration of a silicon CMOS die for the heater and temperature sensor, with multilayer silicone (PDMS) structures namely, fluidic channels and a 1.5-mm diameter 12-muL culture well. A 90-mum-thick PDMS membrane covers the top of the culture well, acting as barrier to contaminants while at the same time allowing the cells to breath and exchange gases with the ambient environment. The packaging for the microsystem includes a flexible polyimide electronic ribbon cable and four fluidic ports that provide external interfaces to electrical energy, closed-loop sensing and electronic control as well as solid and liquid supplies. The complete structure has a size of (2.5times2.5times0.6) cm3. We have employed the device to successfully culture BHK-21 cells autonomously over a three day period in ambient environment

Application of Flexible OLED Display Technology for Electro-Optical Stimulation and/or Silencing of Neural Activity

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 mW/mm2 of instantaneous light intensity using a 13 V, 20 Hz pulse, which meets the minimum reported intensity at ~ 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.

Seamless integration of CMOS and microfluidics using flip chip bonding

We demonstrate the microassembly of PDMS (polydimethylsiloxane) microfluidics with integrated circuits made in complementary metal-oxide-semiconductor (CMOS) processes. CMOS-sized chips are flip chip bonded to a flexible polyimide printed circuit board (PCB) with commercially available solder paste patterned using a SU-8 epoxy. The average resistance of each flip chip bond is negligible and all connections are electrically isolated. PDMS is attached to the flexible polyimide PCB using a combination of oxygen plasma treatment and chemical bonding with 3-aminopropyltriethoxysilane. The total device has a burst pressure of 175 kPA which is limited by the strength of the flip chip attachment. This technique allows the sensor area of the die to act as the bottom of the microfluidic channel. The SU-8 provides a barrier between the pad ring (electrical interface) and the fluids; post-processing is not required on the CMOS die. This assembly method shows great promise for developing analytic systems which combine the strengths of microelectronics and microfluidics into one device.

Application of Flexible OLED Display Technology to Point-of-Care Medical Diagnostic Testing

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 cm2 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.

Experimental and Simulated Cycling of ISFET Electric Fields for Drift Reset

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.

Application of flat panel OLED display technology for the point-of-care detection of circulating cancer biomarkers

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.

Real-time feedback control of pH within microfluidics using integrated sensing and actuation

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.

Theoretical investigation of silicon nanowire pH sensor

In this paper, Si nanowire (NW) sensor in pH detection is presented. The conductance of device is analytically obtained and demonstrated the conductance increases with reducing the oxide thickness. To calculate the electrical conductance of sensor, the diffusion-drift model and nonlinear Poisson-Boltzmann equation are used. To improve the conductance a Si NW sensor with nanoscale side gate voltage is presented and its conductance is theoretically achieved. It is shown the conductance and consequently sensor sensitivity can be enhanced by adding suitable side gate voltage. Finally this effect is compared to the almost similar fabricated structure in literature which has a wire with rectangular cross section.

Pulse width modulation circuit for ISFET drift reset

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.

CMOS potentiostat for chemical sensing applications

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.