Devices, systems, and methods for evaluating cardiac parameters

Patent metadata

Field	Value
Publication number	US-11614437-B2
Application number	US-202016913528-A
Country	US
Kind code	B2
Filing date	Jun 26, 2020
Priority date	Jan 30, 2013
Publication date	Mar 28, 2023
Grant date	Mar 28, 2023

Abstract

In an aspect, disclosed herein are physiological devices and systems, and components thereof, used to evaluate cardiac parameters and arrhythmogenic mechanisms. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A method of determining one or more parameters of a cardiac cell culture, the method comprising:
detecting an electrical property from a monolayer of cardiac myocytes extending over a microelectrode array and a plurality of cantilevers, the electrical property detected using the microelectrode array;
receiving a reading of the electrical property from the microelectrode array at a computing device;
detecting a contractile property from the monolayer of cardiac myocytes using a piezoresistive or piezoelectric property of the plurality of cantilevers;
receiving a reading of the contractile property from the plurality of cantilevers at the computing device;
determining multiple cardiac parameters based on both the electrical property reading and the contractile property reading;
contacting the monolayer of cardiac monocytes with an agent in a mixed medium;
detecting both electrical properties and contractile properties of the monolayer in response to the agent;
receiving readings of both electrical properties and contractile properties of the monolayer in response to the agent;
measuring changes in conduction velocity and peak contractile force in response to the agent; and
creating a fingerprint for the agent based on at least the changes in conduction velocity and peak contractile force.

2. The method of claim 1 , wherein the agent is a metabolic inhibitor, a nutritional supplement, a therapeutic compound, composition, and drug, an investigational compound, composition, and drug, a biosimilar, an agonist, an antagonist, a hormone, a growth factor, a small molecule, a monoclonal antibody, and combinations thereof.

3. The method of claim 1 , further comprising predicting cardiac side effects of the agent based on the one or more of the multiple cardiac parameters.

4. The method of claim 1 , further comprising electrically stimulating the monolayer prior to detecting electrical properties and contractile properties.

5. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is spontaneous beating rate.

6. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is conduction velocity.

7. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is QT interval.

8. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is minimal interspike interval.

9. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is peak contractile force.

10. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is speed of contraction.

11. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is time to relaxation.

12. The method of claim 1 , wherein at least one cardiac parameter of the multiple cardiac parameters is an arrhythmogenic mechanism.

13. The method of claim 12 , wherein the arrhythmogenic mechanism is rhythm generation, and the method further comprises evaluating rhythm generation by measuring at least one of chronotropy and firing frequency dispersion from the monolayer.

14. The method of claim 12 , wherein the arrhythmogenic mechanism is conduction, and the method further comprises evaluating conduction by measuring at least one of conduction velocity, conduction velocity dispersion, and frequency dependence of conduction velocity from the monolayer.

15. The method of claim 12 , wherein the arrhythmogenic mechanism is reentry, and the method further comprises evaluating reentry by measuring at least one of QT interval, QT interval dispersion, reverse use dependence, absolute refractory period, and relative refractory period from the monolayer.

16. The method of claim 1 , further comprising maintaining an environmental temperature of 37 degrees Celsius around the monolayer using a temperature controller.

17. The method of claim 1 , further comprising contacting the monolayer with a mixed medium.

Assignees

• Univ Central Florida Res Found Inc

Inventors

• Hickman James
• Stancescu Maria
• Molnar Peter
• Long Christopher
• Mcaleer Christopher

Classifications

• C12M21/08

  for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00) · CPC title

• C12M41/48

  Automatic or computerized control (automatic analysis G01N35/00) · CPC title

• G01N33/4836 Primary

  using multielectrode arrays · CPC title