Dispensing of a diagnostic liquid onto a diagnostic reagent

• US 20060263902A1
• Filed: 05/23/2005
• Published: 11/23/2006
• Est. Priority Date: 05/23/2005
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Pugia, Michael J., Profitt, James A., Zimmerle, Chris T., Kuo, Hai-Hang, Schulman, Lloyd S.
• Granted Patent: US 8,263,414 B2
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00385 Printing
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 35/1016 Control of the volume dispensed or introduced
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Biological fluid samples are deposited by methods that produce a uniform layer of the sample over a reagent-containing surface. In one embodiment, a nozzle having multiple openings is used to deposit a sample over the reagent-containing surface simultaneously. In an alternative embodiment, single droplets of the sample are deposited in a pattern on the surface, preferably in a sequence of parallel lines. The reaction between the biological sample and the reagents is read from a spectrographic image of the reagent-containing surface obtained by optical methods.

Claims

1. A method of depositing a sample of a biological fluid on a surface having an area containing reagents for reacting with an analyte in said biological fluid, said method comprising:

(a) placing said biological fluid in a reservoir in liquid communication with a nozzle;

(b) dispensing said biological fluid from said nozzle in droplets having diameters in the range of 0.1 to 2 mm onto or adjacent to said reagent-containing area;

(c) reading the results of the reaction between said biological fluid and said reagents from a spectrographic image of the reagent-containing area.

2. A method of claim 1 wherein sufficient droplets are dispensed to cover the area containing reagents simultaneously.

3. A method of claim 1 wherein droplets are dispensed in a sequence of lines to cover the area containing reagents.

4. A method of claim 1 wherein the results of the reaction between said biological fluid and said reagents are read by directing light onto a predetermined portion of said spectroscopic image and measuring the light returned from each portion of said spectroscopic image.

5. A method of claim 1 wherein said nozzles are disposed about 1 to 5 mm from said reagent area.

6. A method of claim 1 wherein nozzles have openings for dispensing said droplets, said openings having diameters between about 100 μ

m and about 1000 μ

m.

7. A method of claim 4 wherein said predetermined portion of said spectroscopic image consists of the entire reagent area.

8. A method of claim 4 wherein said predetermined portion of said spectroscopic image consists of the area contacted by one droplet.

9. A method of claim 8 wherein the results of the reaction between said biological fluid and said reagents are read in a sequence of areas contacted by a sequence of droplets.

10. A method of claim 1 wherein said biological fluid is deposited adjacent to said reagent area.

11. A method of depositing a sample of a biological fluid on a surface having an area containing reagents for reacting with an analyte in said biological fluid, said method comprising:

(a) placing said biological fluid in a reservoir in liquid communication with a nozzle;

(b) placing one or more reagent liquids in one or more reservoirs in liquid communication with said nozzle of (a) or a second nozzle;

(c) dispensing said biological fluid from said nozzle of (a) in droplets having diameters in the range of 0.1 to 2 mm onto or adjacent to said reagent-containing area;

(d) dispensing one or more reagent liquids of (b) from said nozzle of (a) or a second nozzle in droplets having diameters in the range of 0.1 to 2 mm onto or adjacent to said reagent-containing area, said dispensing occurring before, during, or after said dispensing of said biological fluid of (c); and

(e) reading the results of the reaction between said biological fluid and said reagents from a spectrographic image of the reagent-containing area.

12. A method of claim 11, wherein one or more reagent liquids of (b) is (are) dispensed onto said reagent area after prior to dispensing of said biological fluid.

13. A method of claim 11 wherein one or more reagent liquid of (b) is (are) dispensed onto said reagent area after dispensing of said biological fluid.

14. A method of claim 11 wherein said one or more reagent liquids of (b) is (are) dispensed onto said reagent area during dispensing of said biological fluid.

15. A method of claim 11 wherein sufficient droplets are dispensed to cover the area containing reagents simultaneously.

16. A method of claim 11 wherein droplets are dispensed in a sequence of lines to cover the area containing reagents.

17. A method of claim 11 wherein the results of the reaction between said biological fluid and said reagents are read by directing light onto a predetermined portion of said spectroscopic image and measuring the light returned from each portion of said spectroscopic image.

18. A method of claim 11 wherein said nozzles are disposed about 1 to 5 mm from said reagent area.

19. A method of claim 11 wherein nozzles have openings for dispensing said droplets, said openings having diameters between about 100 μ

m and about 1000 μ

m.

20. A method of claim 17 wherein said predetermined portion of said reagent area consists of the entire reagent area.

21. A method of claim 17 wherein said predetermined portion of said reagent area consists of the area contacted by one droplet.

22. A method of claim 21 wherein the results of the reaction between said biological fluid and said reagents are read in a sequence of areas contacted by a sequence of droplets.

23. A method of claim 11, wherein said biological fluid or said reagent liquid is deposited adjacent to said reagent area.

24. An apparatus for measuring the analyte content of a sample of a biological fluid dispensed onto a surface containing reagents for reacting with said analyte comprising:

(a) a nozzle for dispensing said sample of a biological fluid, said nozzle containing one or more openings having diameters between about 100 μ

m and 1000 μ

m and disposed about 1 to 5 mm above said reagent-containing surface;

(b) a reservoir for supplying said biological sample to said nozzle of (a); and

(c) means for positioning said nozzle with respect to said surface or said surface with respect to said nozzle, whereby said nozzle openings dispense said sample of biological fluid onto a predetermined region of said surface containing reagents.

25. An apparatus of claim 24, wherein said predetermined region of said surface is the entire reagent-containing region.

26. An apparatus of claim 24, wherein said predetermined region of said surface is the area contacted by one droplet dispensed by said nozzle openings.

27. An apparatus of claim 24, wherein said predetermined region of said surface is a portion of said surface containing reagents.

28. An apparatus of claim 24, further comprising a means for reading the results of the reaction between said biological fluid and said reagents from a spectrographic image of the reagent-containing surface.

29. An apparatus of claim 28, wherein said means for reading the results of the reaction between said biological fluid and said reagents includes a source of light directed onto a predetermined portion of said spectroscopic image and a detector for measuring the light returned from said portion of said spectroscopic image.

30. An apparatus of claim 29, wherein said predetermined region of said spectroscopic image consists of the entire reagent-containing surface.

31. An apparatus of claim 29, wherein said predetermined region of said spectroscopic image consists of the area contacted by one droplet.

32. An apparatus of claim 29, wherein said predetermined region of said spectroscopic image consist of a portion of said reagent-containing surface.

33. An apparatus of claim 24 further comprising means for dispensing reagent liquids onto said reagent-containing surface.

34. An apparatus of claim 33, wherein said means for dispensing reagent-containing liquids includes a nozzle containing one or more openings having diameters between about 100 μ

m and 1000 μ

m and disposed about 1 to 5 mm above said reagent-containing surface.

35. An apparatus of claim 34 further comprising means for positioning said nozzle with respect to said reagent-containing surface with respect to said nozzle, whereby said nozzle openings dispense said reagent liquids onto predetermined portions of said reagent-containing surface.