Devices and systems for mimicking heart function

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.

1 . An in vitro physiological system for simultaneously measuring contractile properties and electrical properties of a cardiac cell culture, the system comprising:
 a microelectrode array;   one or more cantilevers;   a plurality of cardiac myocytes patterned on the microelectrode array and the one or more cantilevers; and   a medium.   
     
     
         2 . The system of  claim 1 , wherein the one or more cantilevers are generated using a photolithographic process. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The system of  claim 1 , wherein the one or more cantilevers are coated with (3-Trimethoxysilylpropyl)diethylenetriamine. 
     
     
         6 . The system of  claim 1 , wherein the one or more cantilevers are coated with fibronectin. 
     
     
         7 . The system of  claim 1 , wherein the microelectrode array comprises glass. 
     
     
         8 . The system of  claim 1 , wherein the microelectrode array surface is modified using protein adsorption. 
     
     
         9 . The system of  claim 1 , wherein the microelectrode array surface is modified using self-assembled monolayers (SAMs). 
     
     
         10 . The system of  claim 9 , wherein the SAMs comprise extracellular matrix components. 
     
     
         11 . The system of  claim 9 , wherein the SAMs comprise organo silanes containing amine moieties, polyethyleneglycol moieties, or a combination thereof. 
     
     
         12 . The system of  claim 11 , wherein organo silanes containing amine moieties comprise (3-Trimethoxysilylpropyl)diethylenetriamine. 
     
     
         13 . The system of  claim 11 , wherein polyethylene-glycol moieties comprise 2-[Methoxy(polyethyleneoxy)propyl]trimethoxysilane. 
     
     
         14 - 17 . (canceled) 
     
     
         18 . The system of  claim 1 , wherein the cardiac myocytes are derived from differentiated human embryonic stem cells or adult induced human pluripotent stem cells. 
     
     
         19 . (canceled) 
     
     
         20 . The system of  claim 1 , wherein the medium is serum-free. 
     
     
         21 . The system of  claim 20 , wherein the medium comprises epidermal growth factor (EGF). 
     
     
         22 . The system of  claim 20 , wherein the medium comprises hormones, wherein the hormones comprise hydrocortizone and L-thyroxin. 
     
     
         23 - 33 . (canceled) 
     
     
         34 . A method of evaluating the effect of an agent on contractile properties and electrical properties of a cardiac cell culture, the method comprising
 contacting the system of  claim 1  with an agent,   
       measuring contractile properties of the cardiac myocytes, and measuring electrical properties of the cardiac myocytes. 
     
     
         35 . The method of  claim 34 , 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 a combinations thereof. 
     
     
         36 . The method of  claim 34 , wherein the electrical properties comprise arrhythmogenic mechanisms, spontaneous beating rate, conduction velocity, QT interval, minimal interspike interval (upon high frequency stimulation), or a combination thereof. 
     
     
         37 . The method of  claim 34 , wherein the contractile properties comprise peak contractile force, speed of contraction, time to relaxation, or a combination thereof. 
     
     
         38 . The system of  claim 8 , wherein the microelectrode array surface is modified using adsorbed extracellular matrix proteins.