DEVICE TO EXPOSE CELLS TO FLUID SHEAR FORCES AND ASSOCIATED SYSTEMS AND METHODS

• US 20130109012A1
• Filed: 10/29/2012
• Published: 05/02/2013
• Est. Priority Date: 10/27/2011
• Status: Active Grant

• Current Assignee: University of Washington
• Original Assignee: University of Washington Center for Commercialization (University of Washington)
• Inventors: Ting, Lucas, Sniadecki, Nathan J.
• Granted Patent: US 9,140,684 B2
• Time in Patent Office: Days
• US Class Current: 435/6.1
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: C12M 23/20 Material Coatings immunocoatings C12M25/00
• CPC Class Codes: C12M 23/26 flexible flexible containers for laboratory use B01L3/505
• CPC Class Codes: C12M 29/00 Means for introduction, extraction or recirculation of materials, e.g. pumps pumps per se F04B
• CPC Class Codes: C12M 35/04 Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures

Abstract

The present technology relates generally to devices to expose cells to fluid shear forces and associated systems and methods. In particular, several embodiments are directed toward devices to expose cells to fluid shear forces in order to measure changes in internal cell forces. In some embodiments, a fluidic device includes a flow unit configured to induce fluid flow through the device. The device further includes a fluid channel configured to accept a biological sample dispersed on an array of flexible structures. The flow unit can be configured to induce disturbed and/or laminar flow in the fluid channel. The device can further include optical or magnetic detection means configured to measure a degree of deflection of one or more flexible structures in the array.

Claims

1. A fluidics device, comprising:

a flow unit configured to induce fluid flow through the device;

at least one a fluid channel configured to accept a biological sample dispersed on an array of flexible structures, wherein the fluid channel is configured to induce at least one of disturbed or laminar flow in the fluid channel; and

a detection means configured to measure a degree of deflection of one or more flexible structures in the array.

2. The device of claim 1, further comprising at least one of an air chamber or a step positioned in the fluid channel and configured to control a characteristic of fluid flow through the array.

3. The device of claim 1 wherein the biological sample comprises protein solutions, tissues, cells, or fragments of tissues or cells.

4. The device of claim 1 wherein the biological sample comprises at least one of whole blood, platelets, endothelial cells, tumor cells, fibroblasts, smooth muscle cells, cardiomyocytes, white blood cells, red blood cells, or fragments thereof

5. The device of claim 1 wherein the flexible structures comprise microposts made of silicon, polymers, metal, or ceramics.

6. The device of claim 1 wherein individual flexible structures have a diameter from about 1 nm to about 50 μ

m.

7. The device of claim 1 wherein individual flexible structures have an aspect ratio between about 1:

1 and about 1;

100.

8. The device of claim 1 wherein the flow unit is capable of introducing shear stress to the biological sample.

9. The device of claim 8 wherein the flow unit is capable of introducing the shear stress from about −

10 kPa to about 10 kPa.

10. The device of claim 1 wherein the flow unit comprises a positive displacement pump, a piezoelectric pump, a partial vacuum, a diaphragm pump, a hydrostatic pump, or a peristaltic pump.

11. The device of claim 1 wherein individual flexible structures are substantially coated in a non-fouling coating.

12. The device of claim 1 where at least one of the flow unit or the fluid chamber is substantially coated in a non-fouling coating.

13. The device of claim 1 wherein the detection means comprises at least one of optical detection means or magnetic detection means.

14. The device of claim 1 wherein individual flexible structures are substantially coated with at least one binding element.

15. The device of claim 14 wherein the binding element is selected from group consisting of proteins, glycans, polyglycans, glycoproteins, fibrinogen, fibronectin, von Willebrand Factor, collagen, vitronectin, laminin, monoclonal antibodies, polyclonal antibodies, and fragments thereof

16. A shear flow device, comprising:

a fluid chamber configured to accept one or more flexible microposts, the microposts having a biological sample thereon;

a pump configured to induce fluid flow through the fluid chamber, the fluid having laminar flow characteristics in first region and disturbed flow characteristics in a second region; and

detection means configured to quantify a degree of deflection of individual microposts.

17. The device of claim 16 wherein individual microposts comprise a base and a tip, and wherein the detection means are configured to quantify a difference in position between the base and the tip.

18. The device of claim 16, further comprising at least one of a step or a pulse dampener positioned in the fluid chamber and configured to control a characteristic of fluid flow through the chamber.

19. An analytic method, comprising:

placing microposts in a fluid flow chamber, the microposts having a biological sample bound thereto;

flowing fluid over the microposts; and

measuring a deflection of the microposts.

20. The method of claim 19 wherein flowing fluid over the microposts comprises inducing laminar and disturbed flow to the biological sample.

21. The method of claim 20 wherein inducing laminar and disturbed flow comprises flowing fluid over a backward-facing step in the fluid flow chamber, wherein the laminar and disturbed flow occur downstream of the step.

22. The method of claim 19 wherein placing microposts having a biological sample bound thereto comprises placing microposts having human pulmonary artery endothelial cells bound thereto.

23. The method of claim 19, further comprising placing an air chamber in the fluid flow chamber to induce a steady flow rate.

24. The method of claim 19 wherein flowing fluid over the microposts comprises flowing a fluid containing at least one of a drug, reagent, nucleotide, protein, or a material configured to cause the biological sample to contract.