Micro-systems have great potential for use in biology and clinics due to their miniaturization and integration capabilities, which can lead to the development of novel diagnostic and therapeutic devices with improved performance and affordability. This talk focuses on the development of micro-systems: biosensor and actuator, microfluidics, and hybrid MEMS/microfluidics for biological and clinical applications.

A new biosensor and actuator chip was developed for the real-time in-vitro characterization of neuronal cells. Characterizing neuronal cells requires electrical and optical methods for evaluating their electrochemical signaling. However, current technologies suffer from either low noise tolerance or limited transparency for optical observations. This biosensor chip used active thin-film-transistor (TFT) electrodes to improve noise tolerance and was fabricated on a glass substrate to enhance optical observations. These transparent electrodes enable six different investigative modalities, including extracellular voltage recording, electrical stimulation, electrical impedance measurement, and optical imaging, among others. The performance of the biosensor chip was demonstrated using primary mouse neurons. The neuronal activity was recorded in response to their spontaneous activity and to electrical/chemical stimulation.

A novel microfluidic method was developed for studying cell-cell interactions between patient immune cells (T lymphocytes) and cancer cells (leukemic cells). The T lymphocytes are smaller and more deformable than cancer cells. Existing techniques for cell pairing are limited to cells of similar dimensions. This method overcomes the challenge of pairing cells with different dimensions by using hydrodynamic flow focusing in the z-direction to modulate the effective channel height. The method was demonstrated with primary human T lymphocytes, acute myeloid leukemia (AML) cell lines, and primary AML blasts. The activity of paired cells was monitored from early signaling to later functional responses, with more than 80% of paired cells being successfully monitored.

A hybrid MEMS/microfluidics device was developed for high-throughput biophysical cytometry and cell sorting for biological applications such as cancer cell identification. This method demonstrated a practical, optics-free, cost- and labor-efficient way of analyzing multiple biophysical parameters of single cells in a high-throughput format. The practical method provided improved information on single cells without compromising throughput. Integrating more MEMS elements, e.g., additional actuators for mechanical compression and sorting, can lead to a revolutionary single-cell sorter based on biophysical properties.