Acea Biosciences, Inc.

Agilent Technologies, Inc.

Yama A Abassi

Xiaobo Wang

Xiao Xu

Biao Xi

Josephine Atienza

Nan Li

Wen Fu Zhang

Naichen Yu

Jiangbo Gan

Tianxing Wang

Ning Ke

Xiaoyu Zhang

Wei Ouyang

Junquan Xu

Li Zhao

Wei Li

Haoyun An

Manfred Watzele

Alexander Seiler

Donald Thomas

Adrian Papas

Xiabo Wang

Lincoln Muir

Methods of assessing cytolysis of cancer cells are provided, which include: providing a cell-substrate impedance monitoring device operably connected to an impedance analyzer, adding target cells characterized as cancer cells to a well of the device adding effector cells to the well to form a test well, where the effector cells are immune cells obtained or derived from a same patient as the target cells; monitoring cell-substrate impedance of the test well before and after adding the effector cells and optionally deriving an impedance-based parameter from the impedance; and determining effectiveness of effector cell killing of the target cells by comparing the impedance or impedance-based curves over time.

Cell-substrate impedance monitoring of cancer cells

A system for monitoring cells, which includes a device for monitoring cell-substrate impedance, the device having a plurality of wells on a nonconductive substrate, where each of the plurality of wells has an electrode array fabricated on the substrate for measurement of cell-substrate impedance; an impedance analyzer that measures cell-substrate impedance from the plurality of wells; electronic circuitry with multiple analogue-to-digital conversion channels, where the electronic circuitry electrically connects the electrode arrays to the impedance analyzer such that the electrode arrays are electrically monitored at millisecond time resolution; and a software program that analyzes the measured cell-substrate impedance.

Label-free monitoring of excitation-contraction coupling and excitable cells using impedance based systems with millisecond time resolution

Methods of inducing functional maturation of immature cardiomyocytes derived from induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) by electrically pacing the immature cardiomyocytes according to a pulse profile that induces maturation until the immature cardiomyocytes mature into functionally adult cardiomyocytes.

Methods and systems for functional maturation of iPSC and ESC derived cardiomyocytes

Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.

Real time electronic cell sensing systems and applications for cell-based assays

A system for monitoring cell-substrate impedance of excitable cells at millisecond time resolution and methods of assessing cell beating by monitoring cell-substrate impedance of beating cells at millisecond time resolution.

Devices, systems and methods for monitoring excitable cells, such as cardiomyocytes, on microelectrode arrays that couple the electro-stimulation of excitable cells to induce or regulate cardiomyocyte beating and the simultaneous measurement of impedance and extracellular recording to assess changes in cardiomyocyte beating, viability, morphology or electrophysical properties in response to a plurality of treatments.

System and method for monitoring cardiomyocyte beating, viability, morphology and electrophysiological properties

A method of identifying a therapeutic compound for treating cancer in a human subject, the method including: providing a device that measures cell-substrate impedance; culturing cancer cells in the at least two wells, wherein the cancer cells are obtained from a human subject and have a receptor tyrosine kinase (RTK) pathway; adding to a first well a proposed therapeutic compound that affects an RTK pathway and an RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells; and determining a difference in impedance or optionally in cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells of the human subject.

Method of measuring cell-substrate impedance in living cells to identify compounds affecting receptor tyrosine kinase (RTK) activity and pathways for the treatment of cancer

Methods of identifying whether a biologically active agent affects an oncogene addicted pathway within a cancer cell, by introducing a biologically active agent suspected of affecting an oncogene addicted pathway to a first well and a negative control to a second well, and introducing a stimulating agent that stimulates the oncogene addicted pathway to both wells; monitoring cell-substrate impedance of the two wells and optionally determining cell indices from impedance values; generating an impedance based curve for each of the two wells from the impedance values or from the cell indices; comparing the impedance-based curves to determine a degree of similarity; and if significantly different concluding the biologically active agent affects the oncogene addicted pathway within the cancer cells.

Using impedance-based cell response profiling to identify putative inhibitors for oncogene addicted targets or pathways

Devices and methods for performing extracellular recording of cells, such as excitable cells, cardiomyocytes, and cardiomyocyte precursor cells is provided. An exemplary device includes a nonconductive substrate forming or provided as a base of one or more wells; a recording electrode positioned on the substrate within the well, wherein the recording electrode is accessible to cells when a cell sample is added to the device; and a reference electrode positioned within the well in a cell-free zone, the cell-free zone characterized as free from contact with cells when the cell sample is added to the device, thereby preventing contact between cells and the reference electrode.

System and method for monitoring cardiomyocyte beating, viability and morphology and for screening for pharmacological agents which may induce cardiotoxicity or modulate cardiomyocyte function

System and method for monitoring cardiomyocyte beating, viability, morphology, and electrophysiological properties

A system for monitoring cell-substrate impedance of excitable cells and monitoring the beating cycle of cardiomyocytes, the system including: a device for monitoring cell-substrate impedance at 20 millisecond time resolution, the device having one or more wells on a nonconductive substrate, wherein at least one well of the one or more wells comprises an electrode array fabricated on the substrate for measurement of cell-substrate impedance at 20 millisecond time resolution; an impedance analyzer that measures cell-substrate impedance from the at least one well at 20 millisecond time resolution; electronic circuitry that electrically connects the electrode array from the at least one well to the impedance analyzer; and a software program that analyzes the measured cell-substrate impedance.

Use of impedance devices in methods of generating a time dependent cellular profiles (TCRP) for the modulation of oncogene addicted cells and comparing the impedance-based TCRP to controls or knowns to identify signature time dependent cellular profiles.

A method of identifying a potential therapeutic compound that affects a Receptor Tyrosine Kinase (RTK) pathway in cancer cells, which includes: providing a device capable of measuring cell-substrate impedance; culturing cancer cells in serum-free media in at least two wells of the device; adding to a first well a proposed therapeutic compound that affects a RTK pathway and a RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells and optionally determining cell indices from the monitored cell-substrate impedance; and determining a difference in impedance or optionally cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells.

Method of measuring cell-substrate impedance in living cells to identify compounds affecting receptor tyrosine kinase (RTK) activity and pathways

Use of cell-substrate impedance based methods for screening for agonists of G-Protein Coupled Receptors (GPCRs) or inhibitors of a Receptor Tyrosine Kinases (RTKs), identifying compounds that affect GPCR or RTK pathways, validating molecular targets involved in a GPCR or RTK signaling pathways, monitoring dose-dependent functional activation of GPCR or RTK; determining desensitization of a GPCR and identifying a compound capable of affecting RTK activity in cancer cell proliferation.

Dynamic monitoring of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) activity and pathways in living cells using real-time microelectronic cell sensing technology

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San Diego, CA, United States of America

Yama A Abassi