Chemo & Biosensors

According to external page IUPAC (International Union of Pure and Applied Chemistry), a chemical sensor is a device that transforms chemical information, ranging from the concentration of a specific sample component to total composition analysis, into an analytically useful signal. Biosensors are usually considered a subset of chemical sensors making use of or detecting biologically relevant molecules or biological entities.

A variety of CMOS-based microsensor systems has been developed. The transducers include microelectrodes for electrochemical measurements and metallic or semiconducting nanowires. Larger sets of transducers have been combined into arrays and have been monolithically integrated with the needed front-end and signal conditioning circuitry (analog and digital circuitry units).

Enlarged view: Integrated CMOS Electrochemical Sensor Array
Integrated CMOS Electrochemical Sensor Array: 1024 working electrodes (diameter: 25 μm, pitch: 100 μm) and counter and reference electrodes along with 64 current-readout channels and analog-to digital converters.

Integrated microsensor systems offer unprecedented advantages over hybrid or discrete arrays, especially with regard to signal quality, multi-transducer addressing, functionality, and straightforward ways to package such systems. Specific packaging solutions have been developed that enable liquid handling and cell culturing and are aimed at ensuring transducers access while protecting the integrated circuitry.

Applications range from measuring pH-values to detecting metabolites or neurotransmitters, all of which benefit from the possibility to perform the measurements by using multiple transducers in a massively parallel way. The fully integrated array systems are very compact and fit on a thumbnail (chip sizes: 6 x 7 mm2).

Enlarged view: Electrochemical Imaging
Image sequence of amperometric measurements showing the distribution of an aliquot of hydrogen peroxide injected in the center of the liquid phase over the array, taken at 89 frames per second (image size 3.2 by 3.2 mm2).

Another microsensor array includes nanowires as sensor elements, an array of which has been either connected or directly transferred onto a fully developed CMOS chip carrying the readout circuitry.

Enlarged view: Integrated Nanowire Array
Integrated Nanowire Array: Fully integrated system including 16 contact pairs, connected to different numbers of parallel gold nanowires (close-up), as well as on-chip current readout and digitizing circuitry.

Collaborations

University of Basel, Switzerland; EPF Lausanne, Switzerland.

Recent publications

A. Dudina, F. Seichepine, Y. Chen, A. Stettler, A. Hierlemann, U. Frey, "Monolithic CMOS sensor platform featuring an array of 9’216 carbon-nanotube-sensor elements and low-noise, wide-bandwidth and wide-dynamic-range readout circuitry", Sensors & Actuators B (Chemical) 2019, Vol. 279, pp. 255-266 (DOI: 10.1016/j.snb.2018.10.004). external page Online

V. Viswam, R. Bounik, A. Shadmani, J. Dragas, C. Urwyler, J. Boos, M. Obien, J. Müller, Y. Chen, A. Hierlemann, "Impedance spectroscopy and electrophysiological imaging of cells with a high-density CMOS microelectrode array system", IEEE Trans. Biomed. Circuits Syst. 2018, 12 (6), pp. 1356-1368 (DOI: 10.1109/TBCAS.2018.2881044). external page Online

M. Modena, K. Chawla, P. Misun, A. Hierlemann, "Smart cell-culture systems: Integration of sensors and actuators into microphysiological systems", ACS Chem. Biol. 2018, 13 (7), pp 1767–1784 (DOI: 10.1021/acschembio.7b01029). external page Online

J. Dragas, V. Viswam, A. Shadmani, Y. Chen, R. Bounik, A. Stettler, M. Radivojevic, S. Geissler, M. Engelene J. Obien, J. Müller, A. Hierlemann, "In-vitro multi-functional microelectrode array featuring 59760 electrodes, 2048 electrophysiology channels, stimulation, impedance measurement and neurotransmitter detection channels", IEEE Journal of Solid-State Circuits, 2017, Volume 52 (6), pp. 1576-1590 (DOI:10.1109/JSSC.2017.2686580). external page Online

P. Livi, M. Kwiat, A. Shadmani, J. Rothe, G. Navarra, A. Pevzner, A. Stettler, Y. Chen, F. Patolsky, and A. Hierlemann, "Monolithic Integration of a Silicon Nanowire FET Array on a CMOS Chip for Bio-chemical Sensor Applications", Anal. Chem., 2015, 87 (19), pp 9982–9990 (DOI: 10.1021/acs.analchem.5b02604). external page Online

More publications

 

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