In Vitro Multi-Functional Microelectrode Array Featuring 59 760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement, and Neurotransmitter Detection Channels

Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide hig...

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Published in:	IEEE journal of solid-state circuits Vol. 52; no. 6; pp. 1576 - 1590
Main Authors:	Dragas, Jelena, Viswam, Vijay, Shadmani, Amir, Chen, Yihui, Bounik, Raziyeh, Stettler, Alexander, Radivojevic, Milos, Geissler, Sydney, Obien, Marie Engelene J., Muller, Jan, Hierlemann, Andreas
Format:	Journal Article
Language:	English
Published:	New York IEEE 01-06-2017 The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subjects:	Bandwidths Channels CMOS Devices Electric potential Electrodes Electrophysiology Extracellular recording and stimulation high channel count high-density microelectrode array (HD-MEA) Impedance measurement impedance spectroscopy In vitro methods and tests low noise low power Microelectrodes multi-functionality neural interface neurotransmitter detection Neurotransmitters Power consumption pre-charging pseudo-resistor Recording Signal quality Spatial resolution Stimulation switch matrix Switches Switching circuits
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Abstract	Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high-spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system for in vitro applications that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date (4.48 × 2.43 mm 2 ) to accommodate 59760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5-μm electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2048 action potential (AP, bandwidth: 300 Hz-10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz-300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel.
AbstractList	Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high-spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system for in vitro applications that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date ([Formula Omitted] mm2) to accommodate 59 760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5-[Formula Omitted]m electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2048 action potential (AP, bandwidth: 300 Hz–10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz–300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel. Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high-spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system for in vitro applications that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date (4.48 × 2.43 mm 2 ) to accommodate 59760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5-μm electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2048 action potential (AP, bandwidth: 300 Hz-10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz-300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel.
Author	Viswam, Vijay Shadmani, Amir Obien, Marie Engelene J. Radivojevic, Milos Dragas, Jelena Bounik, Raziyeh Chen, Yihui Stettler, Alexander Geissler, Sydney Muller, Jan Hierlemann, Andreas
Author_xml	– sequence: 1 givenname: Jelena surname: Dragas fullname: Dragas, Jelena organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 2 givenname: Vijay surname: Viswam fullname: Viswam, Vijay email: vijay.viswam@bsse.ethz.ch organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 3 givenname: Amir surname: Shadmani fullname: Shadmani, Amir organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 4 givenname: Yihui surname: Chen fullname: Chen, Yihui organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 5 givenname: Raziyeh surname: Bounik fullname: Bounik, Raziyeh organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 6 givenname: Alexander surname: Stettler fullname: Stettler, Alexander organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 7 givenname: Milos surname: Radivojevic fullname: Radivojevic, Milos organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 8 givenname: Sydney surname: Geissler fullname: Geissler, Sydney organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 9 givenname: Marie Engelene J. surname: Obien fullname: Obien, Marie Engelene J. organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 10 givenname: Jan surname: Muller fullname: Muller, Jan organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland – sequence: 11 givenname: Andreas surname: Hierlemann fullname: Hierlemann, Andreas organization: Dept. of Biosyst. Sci. & Eng., ETH Zurich, Basel, Switzerland
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Snippet	Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices...
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SubjectTerms	Bandwidths Channels CMOS Devices Electric potential Electrodes Electrophysiology Extracellular recording and stimulation high channel count high-density microelectrode array (HD-MEA) Impedance measurement impedance spectroscopy In vitro methods and tests low noise low power Microelectrodes multi-functionality neural interface neurotransmitter detection Neurotransmitters Power consumption pre-charging pseudo-resistor Recording Signal quality Spatial resolution Stimulation switch matrix Switches Switching circuits
Title	In Vitro Multi-Functional Microelectrode Array Featuring 59 760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement, and Neurotransmitter Detection Channels
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