Abstract
The adaptation of standard integrated circuit (IC) technology as a transducer in cell-based biosensors in drug discovery pharmacology, neural interface systems and electrophysiology requires electrodes that are electrochemically stable, biocompatible and affordable. Unfortunately, the ubiquitous Complementary Metal Oxide Semiconductor (CMOS) IC technology does not meet the first of these requirements. For devices intended only for research, modification of CMOS by post-processing using cleanroom facilities has been achieved. However, to enable adoption of CMOS as a basis for commercial biosensors, the economies of scale of CMOS fabrication must be maintained by using only low-cost post-processing techniques. This review highlights the methodologies employed in cell-based biosensor design where CMOS-based integrated circuits (ICs) form an integral part of the transducer system. Particular emphasis will be placed on the application of multi-electrode arrays for in vitro neuroscience applications. Identifying suitable IC packaging methods presents further significant challenges when considering specific applications. The various challenges and difficulties are reviewed and some potential solutions are presented.
Highlights
The definition of a ‘biosensor’ as stated by the IUPAC ius ‘a device that uses specific biochemical reactions mediated by isolated enzvmes, immunosystems, tissues, orcranelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals.’ [1]
Of most interest in this review are the electrochemical techniques that are more relevant to integrated circuit (IC)-based biosensors and the packaging technologies that form an integral part of such a device
For deep submicron (
Summary
The definition of a ‘biosensor’ as stated by the IUPAC ius ‘a device that uses specific biochemical reactions mediated by isolated enzvmes, immunosystems, tissues, orcranelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals.’ [1]. Due to the specific materials available in a CMOS process ( aluminium and its oxide), the use of this technology to form a transducer raises the problem of the analyte/electrode interface and potential issues of neurotoxicity [6] This is generally considered to be the main roadblock to CMOS biosensor commercialisation at present. Commercial MEAs are passive components that are custom-fabricated, expensive, have short lifetimes and have no ability to process the recorded signals Because of these shortcomings, analysis of the literature confirms there is significant interest in making the electrode more intelligent by marrying integrated circuit technology with cell-based biosensors, which logically leads to the use of CMOS in this application. The review concludes with an overview of likely further work in this field
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