Whole blood analyses and diffusion apparatus therefor

• US 4,288,228 A
• Filed: 01/31/1979
• Issued: 09/08/1981
• Est. Priority Date: 01/31/1979
• Status: Expired due to Term

• Current Assignee: Technicon Instruments Corporation
• Original Assignee: Technicon Instruments Corporation
• Inventors: Oberhardt, Bruce J.
• Primary Examiner(s): Turk, Arnold
• Application Number:
  US06/007,858
• Time in Patent Office: 951 Days
• Field of Search: 23/230 R, 23/230 B, 422/56, 422/58, 422/66, 422/69, 195/103.5 R, 435/299, 435/301, 435/805, 435/27, 435/25, 435/26
• US Class Current: 436/178
• CPC Class Codes: G01N 33/48 Biological material, e.g. blood, urine G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence; Haemocytometers counting blood corpuscules distributed over a surface by scanning the surface G06M11/02
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

Methods and apparatuses are featured for analyzing whole blood samples by diffusion techniques in porous media. A fluid component of the whole blood is diffused into a thin-film porous medium of a given predetermined volume. Hematocrit dependent errors in diffusion time do not pose a problem in obtaining a precise aliquot of the fluid component of the whole blood due to rapid diffusion and saturation of the fluid component into the porous medium.

In another embodiment, diffusion switches or valves allow for precise aliquots in porous media by control of the diffusion and/or reaction of sample analyte with reagents.

Claims

1. An apparatus for analyzing a whole blood sample, comprising:

a first-thin film porous medium of a given predetermined volume for contact with said whole blood sample to be analyzed, a fluid component of said sample diffusing into said first porous medium;

a second porous medium containing at least one reagent therein;

a fluid barrier interposed between said first and second porous media to isolate said reagent and said fluid component;

means for contacting said first porous medium with said second porous medium, to allow cross-diffusion therebetween, said contacting means including means for displacing said fluid barrier from between at least portions of opposing surfaces of said first and second media and cause said opposing surfaces to contact; and

means to measure a reaction between said reagent and said fluid component in either of said first or second media.

2. The apparatus of claim 1, wherein said porous media comprise gel material.

3. The apparatus of claim 1, wherein said measuring means comprises a colorimeter.

4. The apparatus of claim 1, wherein said measuring means comprises a spectrophotometer.

5. The apparatus of claim 1, wherein said displacing means comprises a vacuum control means for providing a vacuum between said first and second media in order to displace said fluid barrier and to cause said opposing surfaces of said first and second media to contact.

6. The apparatus of claim 1, wherein said fluid barrier is a magnetic substance and said displacing means comprises magnetic means for displacing said magnetic substance and cause said opposing surfaces of said first and second media to contact.

7. The apparatus of claim 1, wherein said displacing means comprises means for pressing said first and second media toward each other to displace said fluid barrier and cause said opposing surfaces of said first and second media to contact.

8. An apparatus for analyzing a fluid sample for an analyte, comprising:

a first porous medium for containing said analyte of said fluid sample;

a second porous medium containing at least one reagent for reaction with said analyte of said fluid sample;

a liquid barrier disposed between said first and second media to isolate said reagent from said analyte; and

means for displacing said liquid barrier from between said first medium and said second medium to allow contact therebetween, whereby said analyte and said reagent can cross diffuse and react.

9. The apparatus of claim 8, wherein said barrier removing means comprises a pressure plate disposed adjacent said porous media for forcing said media into contact with each other, and simultaneously therewith, displacing said barrier from between said first and second media.

10. The apparatus of claim 8, wherein said displacing means defines a well disposed adjacent said media for catching said displaced liquid.

11. The apparatus of claim 8, further comprising a strip adjacent said first porous medium having a graduated series of standards to which said analyte-reagent reaction is compared.

12. The apparatus of claim 8, further comprising a substrate for supporting said first and second media.

13. The apparatus of claim 12, wherein said substrate has a hand-held portion on one end thereof, for dipping said first and second media into a receptacle containing said aqueous fluid sample.

14. The apparatus of claim 8, wherein said displacing means further comprises means for absorbing said displaced liquid.

15. The apparatus of claim 14, wherein said absorbing means comprises a porous wick.

16. A diffusion switch comprising:

a first porous medium adapted to contain a first fluid for diffusion to a second porous medium;

a second porous medium for receiving said first fluid when said second porous medium is in contact with said first porous medium;

a second fluid disposed between said first porous medium and said second porous medium, said second fluid serving as a diffusion barrier between said first medium and said second medium; and

means for displacing said second fluid from between said first medium and said second medium to allow contact therebetween, whereby diffusion of said first fluid can occur from said first medium to said second medium.

17. The diffusion switch of claim 16, further comprising means for restoring said second fluid between said first medium and said second medium after diffusion has occurred.

18. The diffusion switch of claim 16, wherein said first fluid is hydrophobic and said second fluid is hydrophilic.

19. The diffusion switch of claim 16, wherein said first fluid is hydrophilic and said second fluid is hydrophobic.

20. The diffusion switch of claim 16, wherein said second porous medium comprises at least one reagent which is reactive with said first fluid.

21. The diffusion switch of claim 16, wherein said first porous medium comprises a gel material.

22. The diffusion switch of claim 16, wherein said second porous medium comprises a gel material.

23. The diffusion switch of claim 16, wherein said fluid displacing means comprises a pressure control means.

24. The diffusion switch of claim 16, wherein said fluid displacing means comprises an electromagnetic control means.

25. The diffusion switch of claim 16, wherein said fluid displacing means comprises a vacuum control means.

26. The diffusion switch of claim 16, wherein said second fluid comprises a magnetic substance.

27. The diffusion switch of claim 26, wherein said fluid displacing means comprises a magnetic control means.

28. A diffusion switch comprising:

a first porous medium adapted to contain a first fluid comprising a component for diffusion to a second porous medium;

a second porous medium for receiving said component when said second porous medium is in contact with said first porous medium;

a second fluid disposed between said first porous medium and said second porous medium, said second fluid serving as a diffusion barrier between said first medium and said second medium; and

means for displacing said second fluid from between said first medium and said second medium to allow contact therebetween, whereby diffusion of said component can occur from said first medium to said second medium.

29. A method of performing a reaction with an analyte of a sample, comprising the steps of:

(a) diffusing said analyte into a first porous medium;

(b) contacting said first porous medium with a second porous medium to allow diffusion of said analyte into said second porous medium, said second porous medium having at least one first reagent for reaction with said analyte; and

(c) contacting said second porous medium with a third porous medium containing at least one second reagent, said contacting of at least two of said porous media comprising the displacement of a liquid from between said two media.

30. The method of claim 29, wherein said contacting steps (b) and (c) are performed sequentially.

31. The method of claim 29, wherein said contacting steps (b) and (c) are performed concurrently.