Granted Patent B2

US 10,539,523 · App. 14/092,927 · Granted Jan 21, 2020

Inventors: Xiaobo Wang (San Diego, CA); Wei Ouyang (San Diego, CA); Nan Li (San Diego, CA); Tianxing Wang (Hangzhou, CN); Xiaoyu Zhang (San Diego, CA); Xiao Xu (San Diego, CA); Yama A. Abassi (San Diego, CA)

Assignee: ACEA Biosciences, Inc.

G01N27/02

Abstract

Claims (30)

1. A method for monitoring excitable cells, the method comprising:

a) providing a system for monitoring excitable cells, the system comprising a device comprising at least one well, each well having a bottom comprising a nonconductive substrate, wherein the substrate has a surface suitable for attachment of excitable cells; a power source configured to deliver an electrical signal capable of electro-stimulating excitable cells; and an impedance analyzer that resolves consecutive cell-substrate impedance measurements within 10 milliseconds apart, wherein each well comprises:

i) a pair of electro-stimulation electrodes configured to receive the electrical signal from the power source thereby delivering an electro-stimulating signal to the well for electro-stimulation of excitable cells attached to the substrate; and

ii) a pair of impedance monitoring electrodes communicatively coupled to the impedance analyzer permitting cell-substrate impedance monitoring of excitable cells attached to the substrate at 10 millisecond time resolution;

b) adding a sample of cardiomyocyte or cardiomyocyte precursor cells to the device;

c) electro-stimulating the cells to affect cell beating;

d) adding a compound to the well;

e) impedance monitoring the electro-stimulated cells at 10 millisecond time resolution; and

f) assessing the effect of compound administration on cell beating.

2. The method according to claim 1 , wherein the compound's effect on cell beating is assessed by determining a change in beating cycle in response to the addition of the compound.

3. A method for monitoring excitable cells, the method comprising:

a) providing a system for monitoring excitable cells comprising a device comprising at least one well, each well having a bottom comprising a nonconductive substrate, wherein the substrate has a surface suitable for attachment of excitable cells; a power source configured to deliver an electrical signal capable of electro-stimulating excitable cells; an impedance analyzer that resolves consecutive cell-substrate impedance measurements at 10 millisecond time resolution; and an extracellular recording amplifier that measures extracellular potential, wherein each well comprises:

i) a pair of impedance monitoring electrodes communicatively coupled to the impedance analyzer thereby permitting impedance monitoring of excitable cells attached to the substrate; and

ii) an extracellular recording electrode pair communicatively coupled to the extracellular recording amplifier thereby permitting extracellular recording of excitable cells attached to the substrate;

 wherein at least one electrode from the impedance monitoring electrodes or at least one electrode from the extracellular electrode pair is also at least one of a pair of electrostimulation electrodes configured to receive the electrical signal from the power source and delivering an electro-stimulating signal to the well for electro-stimulation of excitable cells attached to the substrate, thereby permitting electro-stimulation of excitable cells and either extracellular recording or impedance monitoring of attached cells using a shared electrode at different time points of a same sample;

b) adding a sample of cardiomyocyte or cardiomyocyte precursor cells to the device;

c) electro-stimulating the cells at a regular time interval to affect excitation-contraction coupling of the cells;

d) adding a compound to the well;

e) impedance monitoring the electro-stimulated cells at 10 millisecond time resolution;

f) extracellular recording of the electro-stimulated cells over time; and

g) assessing the effect of compound administration on cell beating.

4. A method for monitoring excitable cells, the method comprising:

a) providing a system for monitoring excitable cells comprising a device comprising at least one well, each well having a bottom comprising a nonconductive substrate, wherein the substrate has a surface suitable for attachment of excitable cells; a power source configured to deliver an electrical signal capable of electro-stimulating excitable cells; and an impedance analyzer that resolves consecutive cell-substrate impedance measurements within 10 milliseconds apart, wherein each well comprises:

i) a pair of electro-stimulation electrodes configured to receive the electrical signal from the power source thereby delivering an electro-stimulating signal to the well for electro-stimulation of excitable cells attached to the substrate; and

ii) a pair of impedance monitoring electrodes communicatively coupled to the impedance analyzer permitting cell-substrate impedance monitoring of excitable cells attached to the substrate at 10 millisecond time resolution;

b) adding a sample of cardiomyocyte or cardiomyocyte precursor cells to the device;

c) electro-stimulating the cells to affect cell beating;

d) impedance monitoring the electro-stimulated cells at 10 millisecond time resolution; and

e) resolving the beating cycle of the cells.

5. The method according to claim 4 , wherein the beating cycle is resolved using the monitored impedance.

Assignments (2)

Continuity (43)