No abstract

Microelectromechanical system (MEMS) development has become an active area for research in over the last decade. This area has advanced rapidly in recent years due to the potential ability of MEMS devices to perform complex functions in a smaller area. There is also the prospect to develop devices that can (1) be easily manufactured, (2) offer low power consumption, and (3) reduce waste. Especially in the BioMEMS area these advantages are important in terms of applied devices for biosensing, clinical diagnostics, physiological sensing, flow cytometry, and other lab-on-a-chip applications. However, one major obstacle that has been overlooked is the interface of these microdevices with the macroworld. This is critical to enable applications and development of the technology, as currently testing and analysis of data from these devices is mostly limited to generic microprobe stations. New advancements in BioMEMS have to occur in concert with the development of data acquisition systems and signal preprocessors to fully appreciate and test these developing technologies. In this work, we present the development of a cost effective, high throughput data acquisition system (Bio-HD DAQ) and a signal preprocessor for a MEMS-based cell electrophysiology lab-on-a-Chip (CEL-C) device. The signal preprocessor consists of a printed circuit board mounted with the CEL-C device and a 64-channel filter/amplifier circuit array. The data acquisition system includes a high-density crosspoint switching matrix that connects the signal preprocessor to a 16-channel, 18 bit, and 625 kSs DAQ card. Multimodule custom software designed on LABVIEW 7.0 is used to control the DAQ system. While this version of the Bio-HD DAQ system and accompanying software are designed keeping in view the specific requirements of the CEL-C device, it is highly adaptable and, with minor modifications, can become a generic data acquisition system for MEMS development, testing, and application.

In this paper, we report the design, fabrication and characterization of an in-silico cell physiology biochip for measuring Ca 2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real time multidimensional calcium flux patterns around sixteen Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The sixteen microfluidic cell holding pores are 150 by 150 µm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The in-silico cell physiology lab is wire bonded on to a custom PCB for easy interface with a state of the art data acquisition system. The electrodes are coated with a Ca 2+ ion selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Initial characterization results have shown Nernst slopes of 30mv/decade that were stable over a number of measurement cycles. While this work is focused on technology to enable basic research on the Ceratopteris richardii spores, we anticipate that this type of cell physiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique. Future applications include detection of glucose, hormones such as plant auxin, as well as multiple analyte detection on the same chip.

Trans-cellular calcium currents play a central role in the establishment of polarity in differentiating cells. Typically these currents are measured and studied experimentally using ion selective glass microelectrodes. We have recently developed an in silico cell electrophysiology lab-on-a-chip device with the specific science objectives of measuring these transcellular calcium currents in an advanced throughput format. The device consists of 16 pyramidal pores on a silicon substrate with four Ag/AgCl electrodes leading into each pore on the four poles. An SU-8 layer is used as the structural and insulating layer and a calcium ion selective membrane is used to impart ion selectivity to the Ag/AgCl electrodes. In this paper we demonstrate the utility of the cell electrophysiology biochip in measuring these transcellular calcium currents from single cells using the model biological system Ceratopteris richardii. We monitored these fern spores during germination and pharmacologically inhibited biophysical calcium transport. These results demonstrate the utility and versatility of the in silico cell electrophysiology biochip. While this version of the biochip was engineered to fulfill the specific science objectives of measuring trans-cellular calcium currents from Ceratopteris fern spores, the chip can easily be modified for a variety of biomedical and pharmacological applications. Future applications will be based on incorporating multiple analyte detection, amperometry, and biosensors into the device.