System and method for determining a physiological condition of biological tissue
AssigneesTrustees of Boston University, Beth Israel Deaconess Medical Center, Inc.
InventorsBela Suki, Jae Hun Kim, Joseph Hall, Ramaswamy Krishnan, Niccole Schaible
Life of this patent
Estimating the term…
Abstract
Provided herein are systems for determining a stretch condition of a tissue and assessing the stiffness of the tissue. Also provided herein are methods for using the systems for measuring stiffness of a tissue, assessing the effect of an agent on a tissue, and identifying subjects having a disease or disorder associated with increased or decreased stiffness of a tissue.
Claims22
A system for determining a stretch condition of a biological tissue, the system comprising:
- a free-standing composite layer configured to receive a tissue sample of the biological tissue, the free-standing composite layer having a first surface, a second surface that is opposing to the first surface, and two opposing ends, the free-standing composite layer including
- a flexible membrane extending between the two opposing ends,
- a plurality of fiduciary markers interspersed with the flexible membrane, and
- an adhesive area extending at least a portion of the first surface, the adhesive area configured to receive with a no-slip interface the tissue sample;
- and
- a stretching device including
- an indenter having a plurality of inner points configured to contact the second surface of the free-standing composite layer, and
- a rim aligned with the indenter along a central axis, the rim having a plurality of outer points configured to contact the first surface near the two opposing ends of the free-standing composite layer, the plurality of outer points being farther from the central axis than the plurality of inner points;
- wherein at least one of the indenters and the rim is movable to cause an uniform equibiaxial mechanical stretch of the free-standing composite layer and the tissue sample.
The system of claim 10, wherein the displaced image is a displacement map of the plurality of fiduciary markers.
The system of claim 13, wherein the rim is positioned above the indenter.
The system of claim 15, wherein the rim and the indenter are aligned within the rim along a central axis.
A system for determining a stretch condition of a biological tissue, the system comprising:
- a free-standing composite layer configured to receive a tissue sample of the biological tissue, the free-standing composite layer having a first surface, a second surface that is opposing to the first surface, and two opposing ends, the free-standing composite layer including
- a first layer in the form of a flexible membrane that forms a base of the free-standing composite layer,
- a second layer with a tunable stiffness overlaying in a no-slip interface with the first layer, the second layer including a plurality of fiduciary markers, and
- a third layer overlaying in a no-slip interface with the second layer, the third layer having an adhesive surface opposing the no-slip interface with the second layer, the adhesive surface being configured to receive with a no-slip interface the tissue sample;
- and
- a stretching device including
- an indenter having a plurality of inner points configured to contact the second surface of the free-standing composite layer, and
- a rim aligned with the indenter along a central axis, the rim having a plurality of outer points configured to contact the first surface near the two opposing ends of the free-standing composite layer, the plurality of outer points being farther from the central axis than the plurality of inner points;
- wherein at least one of the indenter and the rim is movable to cause an uniform equibiaxial mechanical stretch of the free-standing composite layer and the tissue sample.
A method of classifying a sample, the method comprising
- a) applying radial stretch to a substrate and determining a global radial strain of the substrate layer that is measured when the layer is stretched;
- b) adhering the sample to the substrate;
- and
- c) applying radial stretch the substrate having an adhered sample and determining a global radial strain of the substrate layer that is measured when the layer is stretched,
- wherein measuring is done via a formula of:
- εrro=Δrmemb/rmembo×100
- wherein Δrmemb denotes the change of the radius, and rmembo is the stress-free radius, and the local radial strain εrr that is measured when the substrate and substrate having an adhered sample is stretched, wherein difference between the global radial strain and the local strain is converted to a readout of the stiffness of the sample through a formula:
- ϕ
- =
- ε
- rr
- 0
- -
- ε
- rr
- ε
- rr
- 0
-
- h
- =
- AE
- wherein h is the thickness of the sample, A is a constant that is computed through a linear regression, and E is the stiffness of a sample, and
- wherein samples are classified as either having increased stiffness, decreased stiffness, or normal parameters.
A method of assessing the effect of at least one agent on classification of a sample, the method comprising
- a) applying radial stretch to a substrate and determining a global radial strain of the substrate layer that is measured when the layer is stretched;
- b) adhering the sample to the substrate;
- c) contacting the sample with the at least one agent;
- and
- d) applying radial stretch the substrate having an adhered sample and determining a global radial strain of the substrate layer that is measured when the layer is stretched,
- wherein measuring is done via a formula of:
- εrro=Δrmemb/rmembo×100
- wherein Δrmemb denotes the change of the radius, and rmembo is the stress-free radius, and the local radial strain εrr that is measured when the substrate and substrate having an adhered sample is stretched, wherein difference between the global radial strain and the local strain is converted to a readout of the stiffness of the sample through a formula:
- ϕ
- =
- ε
- rr
- 0
- -
- ε
- rr
- ε
- rr
- 0
-
- h
- =
- AE
- wherein h is the thickness of the sample, A is a constant that is computed through a linear regression, and E is the stiffness of a sample, and
- wherein samples are classified as either having increased stiffness, decreased stiffness, or normal parameters.
(canceled)
(canceled)
Dependencies are inferred from the claim text.