Integrated Sensing: An Integrated Biosensor System for Cellular Studies

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In biological research, the study of cellular functions in vitro is basic to other fields, such as clinical diagnostics, therapy, pharmacological drug screening, and environmental monitoring. In our proposal, biotechnology, silicon micromachining, microelectronics sensor and signal processing technology are used to realize a multi-purpose biological sensor with integrated lownoise signal processing. We research program to for culture, characterization and manipulation of biological cells in silicon chips. In particular, the proposed integrated biosensor system structure can be used as a planar patch-clamp setup for the experimental testing and evaluation of the effect of drugs on prepared ion channels. The proposed device can also act as a miniaturized platform for cell culture and characterization of a cell population together with counting and sizing within the culture chamber. The basic biosensor is a 2D planar 'patch-clamp', which can be employed for sensing the ion-transport through ion channels, the count and size of biological particles, and culturing or sorting cells. We believe the proposed biosensor will enable eventually electronic DNA sequencing through the measurement of ionic current changes as a sequence single-stranded DNA bases pass through a nanoscale pore, which is fabricated and sized to electrically control the single-stranded DNA. A major objective of our proposal is to develop a bio-electronic interface that integrates biological ion channels into a 'nanowell' with associated integrated electronics. The biosensor combines control electronics into a low noise, correlated-double-sampling (CDS)sensitive signal readout with a switched capacitor 'headstage' preamplifier. On-chip electronics will reduce the recording impedance levels, minimize the output leads, prevent crosstalk, and amplify the low-level ion-channel signals. In addition, the biosensor system will enable rapid, computer-aided, automated testing and characterization of ion-channels and their interaction with drugs. The biosensor will also enable experimental verification of ion channel models as well as provide data, which can be analyzed with various algorithms to extract information regarding time and frequency response of the ion channels and their relationship to pharmacological drug investigations. This effort will also explore the use of 'on-chip' adaptive signal processing to electrically model biological cells in real-time with voltage-clamp stimuli applied to the cells.