NEMS sensors for cell force application and measurement

• US 8,857,275 B2
• Filed: 05/01/2012
• Issued: 10/14/2014
• Est. Priority Date: 05/02/2011
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Axelrod, Blake Waters, Popescu, Paula, Roukes, Michael L.
• Primary Examiner(s): Caputo, Lisa
• Assistant Examiner(s): ROY, PUNAM P
• Application Number:
  US13/460,969
• Publication Number:
  US 20130133439A1
• Time in Patent Office: 896 Days
• Field of Search: 738/626.27, 435/287.1, 977/724, 977/958, 977/956
• US Class Current: 73/862.627
• CPC Class Codes: G01L 1/22 using resistance strain gauges
• CPC Class Codes: G01L 5/0033 applying a pulling force
• CPC Class Codes: G01L 5/0038 applying a pushing force
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5073 Stem cells
• CPC Class Codes: Y10S 977/724 Devices having flexible or movable element
• CPC Class Codes: Y10S 977/956 Of mechanical property
• CPC Class Codes: Y10S 977/958 Of biomolecule property

Abstract

An apparatus, system, device, and method provide the ability to measure forces a cell exerts on its surroundings. A platform is suspended across an opening using support legs. The platform is able to move horizontally in a plane of the opening. A piezoresistive strain sensor is integrated into the platform and measures strain induced in the support legs when the platform moves horizontally thereby measuring displacement of the platform.

Claims

1. An apparatus for measuring forces a cell exerts on its surroundings comprising:

a first platform suspended across a first opening between two walls or anchor points, using first support legs, wherein the first platform is able to move horizontally in a first plane of the first opening; and

a first piezoresistive strain sensor integrated into the first platform through at least two of the first support legs, wherein the first piezoresistive strain sensor is configured to measure strain induced in the first support legs when the first platform moves horizontally thereby measuring displacement of the first platform

a second platform suspended across the first opening using second support legs, wherein the second platform is able to move horizontally in the first plane of the first opening; and

a second piezoresistive strain sensor integrated into the second platform, wherein the second piezresistive strain sensor is configured to measure strain induced in the second support legs when the second platform moves horizontally thereby measuring displacement of the second platform;

wherein;

the first platform and the second platform are positioned within a threshold distance of each other;

a cell is placed on each platform and an adherens junction is formed in a gap between the first platform and the second platform; and

a change in force exerted between the first cell and the second cell is measured as a displacement by the first piezoresistive strain sensor and the second piezoresistive strain sensor.

2. The apparatus of claim 1, wherein:

the displacement of the first platform depends linearly on a force applied to move the first platform;

a constant of proportionality of the linear dependence is measured; and

based on the constant of proportionality, the apparatus is used to measure the force.

3. The apparatus of claim 1, wherein the first platform or the second platform is fixed and prevented from moving.

4. The apparatus of claim 1, further comprising:

an actuator configured to control horizontal movement of the first platform, wherein;

the actuator spans between a rigid electrode and the first platform;

the rigid electrode applies bias to the actuator and the force is transferred from the first cell to the second cell through the adherens junction; and

a response to the force is measured by the second piezoresistive strain sensor in the second platform.

5. An apparatus for measuring forces a cell exerts on its surroundings comprising:

a first platform suspended across a first opening between two walls or anchor points, using first support legs, wherein the first platform is able to move horizontally in a first plane of the first opening;

a first piezoresistive strain sensor integrated into the first platform through at least two of the first support legs, wherein the first piezoresistive strain sensor is configured to measure strain induced in the first support legs when the first platform moves horizontally thereby measuring displacement of the first platform; and

an actuator configured to control horizontal movement of the first platform, wherein;

the actuator spans between a rigid electrode and the first platform; and

the rigid electrode applies bias to the actuator.

6. The apparatus of claim 5, wherein:

the first piezoresistive sensor enables real-time measurement of the displacement of the first platform; and

the real-time measurement of the displacement is used in a feedback loop to enable precise displacement of the first platform by the actuator.

7. The apparatus of claim 5, wherein:

the first platform is positioned adjacent to a force sensing beam;

a single cell is positioned on the first platform and attached to the force sensing beam;

when the first platform is moved, a force is applied to the cell that comprises a product of a relative displacement of the first platform and force sensing beam and a force constant of the beam; and

the force sensing beam is used to measure a mechanical response of the cell to the applied force.

8. A method for measuring forces a cell exerts on its surroundings comprising:

moving a first platform horizontally in a first plane of a first opening between two walls or anchor points, wherein the first platform is suspended across the first opening using first support legs; and

measuring strain induced in the first support legs when the first platform moves horizontally thereby measuring displacement of the first platform, wherein the strain is measured using a first piezoresistive strain sensor that is integrated into the first platform through at least two of the first support legs;

wherein;

the displacement of the first platform depends linearly on a force applied to move the first platform;

a constant of proportionality of the linear dependence is measured; and

based on the constant of proportionality, the force is measured.

9. A method for measuring forces a cell exerts on its surroundings comprising:

moving a first platform horizontally in a first plane of a first opening between two walls or anchor points, wherein the first platform is suspended across the first opening using first support legs;

measuring strain induced in the first support legs when the first platform moves horizontally thereby measuring displacement of the first platform, wherein the strain is measured using a first piezoresistive strain sensor that is integrated into the first platform through at least two of the first support legs;

moving a second platform horizontally in the first plane of the first opening, wherein a second platform is suspended across the first opening using second support legs;

placing a cell on each platform to form an adherens junction in a gap between the first platform and the second platform; and

measuring, using a second piezoresistive strain sensor that is integrated into the second platform, strain induced in the second support legs when the second platform moves horizontally thereby measuring displacement of the second platform;

wherein;

the first platform and the second platform are positioned within a threshold distance of each other;

a change in force exerted between the first cell and the second cell is measured as a displacement by the first piezoresistive strain sensor and the second piezoresistive strain sensor.

10. The method of claim 9, wherein the first platform or the second platform is fixed and prevented from moving.

11. The method of claim 9, further comprising:

applying bias, using a rigid electrode, to an actuator, wherein;

the actuator is configured to control horizontal movement of the first platform;

the actuator spans between the rigid electrode and the first platform;

the force is transferred from the first cell to the second cell through the adherens junction; and

measuring a response to the force using the second piezoresistive strain sensor in the second platform.

12. A method for measuring forces a cell exerts on its surroundings comprising:

moving a first platform horizontally in a first plane of a first opening between two walls or anchor points, wherein the first platform is suspended across the first opening using first support legs; and

measuring strain induced in the first support legs when the first platform moves horizontally thereby measuring displacement of the first platform, wherein the strain is measured using a first piezoresistive strain sensor that is integrated into the first platform through at least two of the first support legs;

wherein;

an actuator controls horizontal movement of the first platform;

the actuator spans between a rigid electrode and the first platform; and

the rigid electrode applies bias to the actuator.

13. The method of claim 12, wherein:

the first piezoresistive sensor enables real-time measurement of the displacement of the first platform; and

the real-time measurement of the displacement is used in a feedback loop to enable precise displacement of the first platform by the actuator.

14. The method of claim 12, wherein:

the first platform is positioned adjacent to a force sensing beam;

a single cell is positioned on the first platform and attached to the force sensing beam;

when the first platform is moved, a force is applied to the cell that comprises a product of a relative displacement of the first platform and force sensing beam and a force constant of the beam; and

the force sensing beam is used to measure a mechanical response of the cell to the applied force.