Harvard College

Wenxuan Wu

Hongkun Park

Donhee Ham

Jeffrey T Abbott

Tianyang Ye

Han Sae Jung

Henry Julian Hinton

Keith Krenek

Disclosed herein are an apparatus for electrically assessing and/or manipulating cells. One aspect is directed to electrically mapping cells on the surface of the semiconductor substrate via cross-electrode impedance measurements. Further according to some aspects, the electrode array allows for spatially addressable electrical stimulation and/or recording of electrical signals in real-time using the CMOS circuitry. Some of these aspects are directed to using an electrode array to perform cell patterning through electrochemical gas generation, and extracellular electrochemical mapping.

Systems and methods for patterning and spatial electrochemical mapping of cells

Disclosed herein are semiconductor devices to provide a CMOS-compatible, wafer-scale, multi-well platform that can be used for biomedical or other applications, and methods to operate the same. In some embodiments, circuitry is provided underneath a multiple-well array to electrically interface with electrodes in the wells. To interface with electrodes in a large array, circuitry may be fabricated on a single silicon (Si) wafer having a dimension that is at least the same or larger than that of the multiple-well array. According to one aspect of the present disclosure, standard CMOS fabrication process such as those known to be used in a standard semiconductor foundry may be used without expensive customization for complex fabrication procedures. This may help the production cost to be lowered in some cases.

Complementary metal-oxide-semiconductor (CMOS) multi-well apparatus for electrical cell assessment

Methods and systems for monitoring the activity of electrogenic networks are described. One representative system includes an array of electrode coupled to an analyzer having a stimulator and a receiver. The electrode is placed in contact with an electrogenic cell. The electrodes can be shaped as nanowires, tubes, cavities and/or cones. The analyzer may be configured to operate in a voltage stimulation mode, in which the cells are stimulated via voltages and monitored via current, or in a current stimulation mode, in which the cells are stimulated via currents and monitored via voltages. The analyzers may be arranged as single-stage amplifiers, and may include a feedback loop shared between the stimulation signal path and the sensing signal path. The feedback loop may be arranged to provide overlapping stimulation and sensing of the electrogenic network's cells.

Electronic circuits for analyzing electrogenic cells and related methods

Methods and systems for stimulating and monitoring electrogenic cells are described. Some systems for stimulating electrogenic cells are based on the injection of electric currents into the cells via electrodes connected to the cells. Such stimulators may comprise an impedance element having an input terminal and an output terminal coupled to an electrode, and a voltage follower coupled between the input terminal and the output terminal of the impedance element, the voltage follower being configured to maintain a substantially constant voltage between the input terminal and the output terminal of the impedance element. The impedance element may comprise one or more switched capacitors at least in some embodiments. In some embodiments, the voltage follower may be implemented using a source follower.

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Cambridge, MA, United States of America

Wenxuan Wu