Methods and systems for using actuated surface-attached posts for assessing biofluid rheology

• US 8,586,368 B2
• Filed: 06/25/2010
• Issued: 11/19/2013
• Est. Priority Date: 06/25/2009
• Status: Active Grant

• Current Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Superfine, Richard, Spero, Richard Chasen, Shields, Adam Richard, Evans, Benjamin Aaron, Fiser, Briana Lee
• Primary Examiner(s): Wallenhorst, Maureen
• Application Number:
  US13/380,564
• Publication Number:
  US 20120156791A1
• Time in Patent Office: 1,243 Days
• Field of Search: 436/63, 436/69, 436/73, 436/149, 436/150, 436/151, 436/164, 436/165, 422/68.1, 422/73, 422/82.01, 422/82.05, 422/82.09, 422/551, 422/552, 435/2, 435/13, 435/29, 435/287.1, 435/288.3, 435/288.4, 435/288.7, 600/369, 73/540.1, 73/644.1, 73/644.2, 73/644.3
• US Class Current: 436/69
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B29C 39/026 characterised by the shape of the surface
• CPC Class Codes: B29K 2083/00 Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material
• CPC Class Codes: B29K 2869/00 Use of PC, i.e. polycarbonates or derivatives thereof as mould material
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: C23F 1/04 Chemical milling
• CPC Class Codes: G01N 11/16 by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/02827 Elastic parameters, strength or force
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56

Abstract

Methods, systems, and computer readable media for using actuated surface-attached posts for assessing biofluid rheology are disclosed. According to one aspect, a method for testing properties of a biofluid specimen includes placing the specimen onto a micropost array having a plurality of microposts extending outwards from a substrate, wherein each micropost includes a proximal end attached to the substrate and a distal end opposite the proximal end, and generating an actuation force in proximity to the micropost array to actuate the microposts, thereby compelling at least some of the microposts to exhibit motion. The method further includes measuring the motion of at least one of the microposts in response to the actuation force and determining a property of the specimen based on the measured motion of the at least one micropost.

Claims

1. A method of testing properties of a biofluid specimen, comprising:

placing the biofluid specimen onto a micropost array having a plurality of microposts extending outwards from a substrate, wherein each micropost includes a proximal end attached to the substrate and a distal end opposite the proximal end;

generating an actuation force in proximity to the micropost array to actuate the microposts, thereby compelling at least some of the microposts to exhibit motion;

measuring the motion of at least one of the at least some microposts in response to the actuation force; and

determining a property of the biofluid specimen based on the measured motion of the at least one micropost.

2. The method of claim 1 wherein the method is performed by at least one of a handheld device, a point of care device, a bench-top device, and a high-throughput device.

3. The method of claim 1 wherein the at least some microposts include at least one of a metallic, magnetic, thermal, optical, and ferroelectric material.

4. The method of claim 3 wherein the material comprises a shell around at least a portion of the height of the at least some microposts.

5. The method of claim 3 wherein the magnetic material comprises a single piece of ferromagnetic material.

6. The method of claim 1 wherein the microposts include a plurality of nanoparticles.

7. The method of claim 6 wherein the plurality of nanoparticles includes at least one of a metallic, magnetic, thermal, optical, and ferroelectric characteristic.

8. The method of claim 7 wherein the plurality of nanoparticles is concentrated proximal to the distal end of the microposts.

9. The method of claim 1 wherein the actuation force is generated as one of an impulse force, a frequency-dependent force, and amplitude-dependent force.

10. The method of claim 1 wherein the motion is measured using at least one of a magnetic, optical, electric, and sonic measurement means.

11. The method of claim 10 wherein the magnetic means includes at least one of a magnetic pickup coil, a microelectromechanical (MEM) system, and a solid state system.

12. The method of claim 10 wherein the optical means includes at least one of an imaging system, a scattered-light measuring system, a reflected-light measuring system, and a transmitted-light measuring system.

13. The method of claim 1 wherein the actuation force includes at least one of a magnetic force, an electrical force, a thermal force, a sonic force, and force associated with a fluid flow.

14. The method of claim 1 wherein determining the property of the specimen includes determining at least one of a clotting property, a viscoelastic property, a degradation property, a rheological property, a physical property, and a chemical property of the specimen.

15. A system for testing properties of a biofluid specimen, comprising:

a micropost array having a plurality of microposts extending outwards from a substrate and into a biofluid specimen located on the substrate, wherein each micropost includes a proximal end attached to the substrate and a distal end opposite the proximal end;

an actuation unit for generating an actuation force in proximity to the micropost array to actuate the microposts, thereby compelling at least some of the microposts to exhibit motion;

a motion detection unit for measuring the motion of at least one of the at least some microposts in response to the actuation force; and

a processing unit for determining a property of the specimen based on the measured motion of the at least one micropost.

16. The system of claim 15 wherein the system is one of a handheld device, a point of care device, a bench-top device, and a high-throughput device.

17. The system of claim 15 wherein the processing unit is located remotely from and communicates wirelessly with the motion detection unit.

18. The system of claim 15 wherein the micropost array is positioned on a receiving end of a tab for receiving a single biofluid specimen, and wherein the tab is brought in proximity to the actuation unit.

19. The system of claim 15 wherein the at least some microposts include at least one of a metallic, magnetic, thermal, optical, and ferroelectric material.

20. The method of claim 19 wherein the material comprises a shell around at least a portion of the height of the at least some microposts.

21. The system of claim 19 wherein the magnetic material comprises a single piece of ferromagnetic material.

22. The system of claim 15 wherein the microposts include a plurality of nanoparticles.

23. The system of claim 22 wherein the plurality of nanoparticles includes at least one of a metallic, magnetic, thermal, optical, and ferroelectric characteristic.

24. The system of claim 23 wherein the plurality of nanoparticles is concentrated proximal to the distal end of the microposts.

25. The system of claim 15 wherein the microposts are composed of metallic material.

26. The system of claim 15 wherein the actuation force is generated as one of an impulse force, a frequency-dependent force, and amplitude-dependent force.

27. The system of claim 15 wherein the motion detection unit measures motion using at least one of a magnetic, optical, electric, and sonic measurement means.

28. The system of claim 27 wherein the magnetic means includes at least one of a magnetic pickup coil, a microelectromechanical (MEM) system, and a solid state system.

29. The system of claim 27 wherein the optical means includes at least one of an imaging system, a scattered-light measuring system, a reflected-light measuring system, and a transmitted-light measuring system.

30. The system of claim 15 wherein the actuation force includes at least one of a magnetic force, an electrical force, a thermal force, a sonic force, and force associated with a fluid flow.

31. The system of claim 15 wherein determining the property of the specimen includes determining at least one of a clotting property, a viscoelastic property, a degradation property, a rheological property, a physical property, and a chemical property of the specimen.

32. The system of claim 15 further comprising:

a multiwell plate including a plurality of wells for holding a plurality of specimens, each well including at least a portion of the micropost array such that the microposts extend from a surface in each well, and wherein the actuation unit further comprises;

a multiforce plate having disposed thereon a plurality of field-forming poles, each field-forming pole being located on the multiforce plate at a location corresponding to at least one of the wells in the multiwell plate, and

an exciter assembly having excitation poles disposed thereon at locations corresponding to the field-forming poles, for magnetically or electronically coupling to the field-forming poles, and for producing a magnetic or electric effect, wherein the coupled field-forming poles apply the magnetic or electric effect to the microposts located in the wells of the multiwell plate to affect movement of the microposts.

33. A computer readable medium having stored thereon computer executable instructions that when executed by a processor of a computer control the computer to perform steps comprising:

generating an actuation force in proximity to a micropost array, having a plurality of microposts extending outwards from a substrate, wherein each micropost includes a proximal end attached to the substrate and a distal end opposite the proximal end, and wherein the micropost array includes a biofluid specimen, so as to compel at least some of the microposts to exhibit motion;

measuring the motion of at least one of the at least some microposts in response to the actuation force; and

determining a property of the specimen based on the measured motion of the at least one micropost.