Multi-well mechanical stimulation systems and incubators

Patent metadata

Field	Value
Publication number	US-2020270561-A1
Application number	US-201816753710-A
Country	US
Kind code	A1
Filing date	Oct 19, 2018
Priority date	Oct 19, 2017
Publication date	Aug 27, 2020
Grant date	—

Abstract

Disclosed mechanical stimulator systems can maintain the sterility of biological samples within a multi-well plate while mechanically stimulating the samples. The systems disclosed herein allow for the individual activation by mechanical compression of a high number of samples at the same time, while maintaining sterility of the samples. The well plates, guides, actuations pistons, and other components of the disclosed systems can be configured to be contained in or adjacent to an incubator that can control properties such as gas levels and temperature while at the same time allowing for the mechanical actuation of the biological samples.

First claim

1 . A system for mechanically stimulating biological samples in a multi-well plate, comprising:
a plurality of guides configured to be inserted into wells of a multi-well plate, with the wells containing biological samples; a plurality of pistons configured to fit into the guides and reciprocate within the guides to provide mechanical stimulation to the biological samples in the wells.

2 . The system of claim 1 , wherein at least some of the guides are attached together in a fixed group of guides spanning plural of the wells.

3 . The system of claim 1 , wherein the guides comprise vertical guide channels to guide vertical reciprocation motion of the pistons within the guides.

4 . The system of claim 1 , wherein the guides comprise a stop that sets a maximum depth that the pistons can be inserted into the wells.

5 . The system of claim 1 , wherein the pistons comprise radially extending flanges that interface with the guides to restrict motion of the pistons to vertical reciprocation.

6 . The system of claim 1 , wherein the pistons comprise vertical channels that allow fluid from the wells to pass up through the pistons when the pistons move down into the wells.

7 . The system of claim 6 , wherein the pistons comprise open spaces to receive displaced fluid from the wells when the pistons move down into the wells.

8 . The system of claim 1 , further comprising a membrane that spans across upper sides of the pistons and is sized to cover the multi-well plate when the system is applied to the multi-well plate, the membrane providing a shield to maintain sterility of the biological samples in the wells.

9 . The system of claim 8 , wherein the membrane comprises a plurality of deformed pockets corresponding to the locations of the pistons, the pockets allowing reciprocation of the pistons with little or no restriction from the membrane.

10 . The system of claim 8 , further comprising a plurality of supports coupled to upper ends of the pistons, with the membrane passing between the supports and the pistons, wherein the supports are configured to interface with a mechanical actuation mechanism to drive the pistons.

11 . The system of claim 8 , further comprising a lid having holes through which the pistons pass, the lid being secured to the membrane, wherein the lid is configured to cover the top of the multi-well plate and help maintain sterility of the biological samples in the wells.

12 . The system of claim 1 , further comprising an incubator that at least partially contains the multi-well plate with the guides and pistons coupled to the wells.

13 . The system of claim 12 , wherein the incubator comprise a fluid inflow port and fluid outflow port and is configured to control a flux of fluid through the wells while the samples in the wells are mechanically stimulated by the pistons.

14 . The system of claim 12 , wherein the incubator comprises a temperature sensor and is configured to control the temperature of the samples in the wells while the samples in the wells are mechanically stimulated by the pistons.

15 . The system of claim 12 , wherein the incubator comprises a gas sensor and is configured to control gas concentration levels in the wells while the samples in the wells are mechanically stimulated by the pistons.

16 . The system of claim 12 , wherein the incubator is divided in two separated monophasic spaces for gas and liquid.

17 . The system of claim 16 , wherein the incubator is divided by a septum such that space inside the incubator available for the fluid transfer is constant and separated from the multi-well plate.

18 . The system of claim 1 , further comprising a motorized actuation system that engages the pistons to cause a selected reciprocation motion of the pistons.

19 . The system of claim 1 , wherein the system is capable of determining a Young's Modulus of viscoelastic biological samples within the wells.

20 . A method of mechanically stimulating a plurality of biological samples using the system of claim 1 , by reciprocating the pistons within the guides to apply mechanical pressure to the biological samples within the wells.

Assignees

• Univ Of Pittsburgh - Of The Commonwealth System Of Higher Education
• Fond Rimed

Inventors

• Marino Davide
• Gottardi Riccardo
• Tuan Rocky Sung Chi

Classifications

• B01L2300/0861

  Configuration of multiple channels and/or chambers in a single devices · CPC title

• C12M23/38

  Caps; Covers; Plugs; Pouring means · CPC title

• C12M37/04

  Seals · CPC title

• B01L2200/0647

  Handling flowable solids, e.g. microscopic beads, cells, particles · CPC title

• C12M27/00

  Means for mixing, agitating or circulating fluids in the vessel (by introduction of gas C12M29/06, C12M29/14, mixing in general or mixers per se B01F; mixing in apparatus for chemical or physical processes B01J) · CPC title