Method of photometric in vitro determination of the content of an analyte in a sample of whole blood

• US 5,288,646 A
• Filed: 06/21/1991
• Issued: 02/22/1994
• Est. Priority Date: 12/22/1988
• Status: Expired due to Term

• Current Assignee: Radiometer A/S (Danaher Corporation)
• Original Assignee: Radiometer A/S (Danaher Corporation)
• Inventors: Lundsgaard, Finn C., Andersen, Willy, Jensen, Niels-Henrik
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US07/720,531
• Time in Patent Office: 977 Days
• Field of Search: 422/82.05, 422/82.06, 422/82.11, 436/164, 436/165, 436/68, 436/74, 128/634, 128/633, 356/39, 356/246, 356/434
• US Class Current: 436/165
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/036 transformable, modifiable
• CPC Class Codes: G01N 2021/0364 flexible, compressible
• CPC Class Codes: G01N 2021/3148 using three or more wavelengths
• CPC Class Codes: G01N 2021/3166 using separate detectors and filters
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 2021/8405 Application to two-phase or mixed materials, e.g. gas dissolved in liquids
• CPC Class Codes: G01N 2035/00306 Housings, cabinets, control panels (details)
• CPC Class Codes: G01N 2035/00316 Detecting door closure
• CPC Class Codes: G01N 2035/1062 for testing the liquid while it is in the transfer device
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/251 Colorimeters; Construction thereof
• CPC Class Codes: G01N 21/255 Details, e.g. use of specially adapted sources, lighting or optical systems
• CPC Class Codes: G01N 21/276 with alternation of sample and standard in optical path
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/78 : producing a change of colour
• CPC Class Codes: G01N 21/80 : Indicating pH value
• CPC Class Codes: G01N 2201/0407 : with multiple optical units, e.g. one per sample
• CPC Class Codes: G01N 2201/0476 : Keyboard controlled, e.g. for plural analysis at one sample, channel selection, coding
• CPC Class Codes: G01N 2201/0618 : Halogene sources
• CPC Class Codes: G01N 2201/1288 : Calibration medium periodically inserted in one cell
• CPC Class Codes: G01N 33/4925 : measuring blood gas content, e.g. O2, CO2 , HCO3
• CPC Class Codes: G01N 33/497 : of gaseous biological material, e.g. breath

Abstract

A sampling device for photometric determination of the content of an analyte in a sample of whole blood has at least one measuring chamber having locally transparent wall parts, at least one wall part being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber, with a transparent body having a radiation transmission characteristic dependent upon the concentration of a predetermined analyte in the whole blood sample disposed between the wall parts. The sampling device is employed in an analyzer for photometric determination of the content of analyte in a sample of whole blood and in a method of photometric in vitro determination of the content of an analyte in a sample of whole blood. In the method, a sample of whole blood is transferred directly from an in vivo locality to the sampling device, the measuring chamber therein is deformed in a controlled manner to substantially drain the whole blood from the measuring chamber, radiation is transmitted through the substantially drained measuring chamber, detected, and the analyte content determined. A measuring chamber for photometric determination of an analyte in a sample of whole blood has locally transparent wall parts, at least one being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber, and a transparent body disposed between the wall parts. The measuring chamber is employed in an analyzer and in a method for the photometric determination of an analyte in a sample of whole blood.

Claims

1. A sampling device for photometric determination of the content of an analyte in a sample of whole blood, comprising:

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole body sample from the at least one measuring chamber for photometric analysis, said at least one measuring chamber further including a transparent body disposed between said locally transparent wall parts the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact o said analyte with said transparent body, a detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the construction of said analyte in the whole body sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence said whole blood sample can be performed.

2. A sampling device according to claim 1, wherein the transparent body has two planoparallel surfaces.

3. A sampling device according to claim 2 wherein the locally transparent wall parts of the at least one measuring chamber are planoparallel parts extending parallel to the planoparallel surfaces of the transparent body.

4. A sampling device according to claim 1, wherein one of the locally transparent wall parts is so deformable that it can be brought into abutment with the transparent body while displacing any sample of whole blood within the at least one measuring chamber.

5. A sampling device according to claim 1, wherein both of the locally transparent wall parts are so deformable that they can be brought into abutment with the transparent body while displacing any sample of whole blood within the at least one measuring chamber.

6. A sampling device according to claim 1, wherein one of the locally transparent wall parts is so deformable that it can be brought into abutment with the transparent body which simultaneously causes the transparent body to be brought into abutment with the opposite locally transparent wall part while displacing any sample of whole blood within the at least one measuring chamber.

7. A sampling device according to claim 1, wherein an indicator is fixed to the transparent body, for reaction with said analyte, the radiation transmission characteristics of the indicator varying the content of the analyte to be determined in the sample of whole blood.

8. A sampling device according to claim 7, wherein the indicator is a pH indicator having a pronounced pH sensitivity at physiological blood pH values.

9. A sampling device according to claim 1, wherein the transparent body comprises a polymer material containing --OH groups having a pH indicator immobilized thereto.

10. A sampling device according to claim 9, wherein the polymer material containing --OH groups is selected from the group consisting of cellulose and cellphone material.

11. A sampling device according to claim 1, wherein the transparent body comprises a transparent material that is able to absorb carbon dioxide.

12. A sampling device according to claim 11, wherein the transparent material is silicone rubber.

13. An analyzer for photometric determination of the content of an analyte in a sample of whole blood comprising:

a) a radiation source;

b) means for detecting radiation transmitted from the radiation source;

c) a sampling device comprising;

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis.

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transport body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body, a detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed;

d) a sampling device station containing the sampling device; and

e) means for deforming the locally transparent wall parts of the at least one measuring chamber in the sampling device in a controlled manner to reduce the volume of the at least one measuring chamber such that the sample of whole blood is substantially drained from the at least one measuring chamber, wherein the sampling device station of step (d) is arranged relative to the radiation source and the radiation detection means so that the radiation transmitted from the radiation source will pass through the at least one volume-reduced measuring chamber to the radiation detection means.

14. An analyzer according to claim 13, wherein the means from deforming the locally transparent wall parts of the at least one measuring chamber in the sampling device displaces and deforms one of the locally transparent wall parts of the at least one measuring chamber such that the deformed and displaced locally transparent wall part is brought into abutment with one surface of the transparent body and the opposite surface of the transparent body is brought into abutment with the other locally transparent wall part of the measuring chamber.

15. A method of photometric in vitro determination of the content of an analyte in a sample of whole blood, comprising the steps of:

a) transferring a sample of whole blood directly from an in vivo locality to a sampling device, wherein the sampling device comprises;

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis,

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed;

b) placing the sampling device in a sampling device station wherein the sampling device station is arranged relative to an optical system comprised of a radiation source and a means for detecting radiation such that the sampling device is located between the radiation source and the radiation detection means;

c) deforming the at least one measuring chamber of the sampling device in a controlled manner to reduce the volume of the at least one measuring chamber thereby substantially draining the sample of whole blood from the measuring chamber;

d) transmitting radiation from the radiation source through the deformed, substantially drained at least one measuring chamber to the radiation detector;

e) detecting the radiation transmitted in step d); and

f) determining the analyte content of the sample of whole blood from the radiation detected in step e).

16. A method according to claim 15, wherein the transparent body has two planoparallel surfaces arranged perpendicular to the radiation transmitted from the radiation source.

17. A method according to claim 16, wherein the locally transparent wall parts of the at least one measuring chamber comprise planoparallel parts extending parallel to the planoparallel surfaces of the transparent body within the sampling device.

18. A method according to claim 15, wherein the transparent body further comprises an indicator fixed thereto for reaction with said analyte, the radiation transmission characteristics of the indicator varying with the content of the analyte to be determined in the sample of whole blood.

19. A method according to claim 18, wherein the analyte is H⁺.

20. A method according to claim 19, wherein the indicator is a pH indicator having a pronounced pH sensitivity at physiological blood pH values.

21. A method according to claim 20, wherein the pH indicator is a compound comprising the functional group --SO₂ --CH₂ --CH₂ --O--SO₃ H.

22. A method according to claim 20, wherein the pH indicator is fixed to the transparent body within the sampling device by covalent bonding.

23. A method according to claim 22, wherein the transparent body comprises a polymer material containing --OH groups having said pH indicator immobilized thereto.

24. A method according to claim 23, wherein the polymer material containing --OH groups is selected from the group consisting of cellulose and cellophane material.

25. A method according to claim 15, wherein the analyte in the sample of whole blood is a blood electrolyte.

26. A method according to claim 15, wherein the analyte in the sample of whole blood is a cationic blood component.

27. A method according to claim 26, wherein the cationic blood component is selected from the group consisting of H⁺, Li⁺, Na⁺, K⁺, Ca⁺⁺, and Mg⁺⁺.

28. A method according to claim 15, wherein the analyte in the sample of whole blood is carbon dioxide.

29. A method according to claim 28, wherein the transparent body within the sampling device comprises a transparent material that is able to absorb carbon dioxide.

30. A method according to claim 29, wherein the transparent material of the transparent body is silicone rubber.

31. A measuring chamber for photometric determination of the content of an analyte in a sample of whole blood, comprising:

two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber for photometric analysis,

said measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed.

32. A measuring chamber according to claim 31, wherein the transparent body has two planoparallel surfaces.

33. A measuring chamber according to claim 32, wherein the locally transparent wall parts of the measuring chamber are planoparallel parts extending parallel to the planoparallel surface of the transparent body.

34. A measuring chamber according to claim 31, wherein one of the locally transparent wall parts of the measuring chamber is so deformable that it can be brought into abutment with the transparent body while displacing any sample of whole blood within the measuring chamber.

35. A measuring chamber according to claim 31, wherein both of the locally transparent wall parts of the measuring chamber are so deformable that they can be brought into abutment with the transparent body while displacing any sample of whole blood within the measuring chamber.

36. A measuring chamber according to claim 31, wherein one of the locally transparent wall parts of the measuring chamber is so deformable that it can be brought into abutment with the transparent body which simultaneously causes the transparent body to be brought into abutment with the opposite locally transparent wall part of the measuring chamber, while displacing any sample of whole blood within the measuring chamber.

37. An analyzer for photometric determination of the content of an analyte in a sample of whole blood, comprising:

a) a radiation source;

b) means for detecting radiation transmitted from the radiation source;

c) at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis,

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing acid analyte or reacting with said analyte such that upon contact of said analyte with said transparent body and detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed,

wherein the at least one measuring chamber is arranged relative to the radiation source and the radiation detection means so that the radiation transmitted from the radiation source will pass through the at least one measuring chamber to the radiation detection means; and

d) means for deforming at least one of the locally transparent wall parts of the at least one measuring chamber in a controlled manner to reduce the volume of the at least one measuring chamber such that the sample of whole blood is substantially drained from the at least one chamber.

38. An analyzer according to claim 37, wherein the means for deforming at least one of the locally transparent wall parts of the at least one measuring chamber displaces and deforms one of the locally transparent wall parts of the at least one measuring chamber such that the deformed and displaced locally transparent wall part is brought into abutment with one surface of the transparent body and the opposite surface of the transparent body is brought into abutment with the other locally transparent wall part of the at least one measuring chamber.

39. A method of photometric in vitro determination of the content of an analyte in a sample of whole blood, comprising the steps of:

a) transferring a sample of whole blood to a measuring chamber which has two locally transparent wall parts located opposite one another at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber for photometric analysis,

said measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte said that upon contact of said analyte with said transparent body a detectable change in a radiation transmission characteristic of said transparent body occurs which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed.

the measuring chamber being arranged relative to an optical system comprised of a radiation source and a means for detecting radiation such that the measuring chamber is located between the radiation source and the radiation detection means;

b) deforming the measuring chamber in a controlled manner to reduce the volume of the measuring chamber thereby substantially draining the sample of whole blood from the measuring chamber;

c) transmitting radiation from the radiation source through the deformed, substantially drained measuring chamber to the radiation detector;

d) detecting the radiation transmitted in step c); and

e) determining the analyte content of the sample of whole blood from the radiation detected in step d).

40. A method according to claim 39, wherein the transparent body has two planoparallel surface arranged perpendicular to the radiation transmitted from the radiation source.

41. A method according to claim 40, wherein the locally transparent wall parts of the measuring chamber comprise planoparallel parts extending parallel to the planoparallel surfaces of the transparent body within the measuring chamber.

42. A method according to claim 39, wherein the transparent body further comprises an indicator fixed thereto for reaction with said analyte, the radiation transmission characteristics of the indicator varying with the content of the analyte to be determined in the sample of whole blood.

43. A sampling device for photometric determination of the content of an analyte in a sample of whole blood, comprising:

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body, a detectable radiation modification is caused in said transparent body which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation modification after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed.

44. An analyzer for photometric determination of the content of an analyte in a sample of whole blood comprising;

a) a radiation source;

b) means for detecting radiation transmitted from the radiation source;

c) a sampling device comprising;

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis,

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transport body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body, a detectable radiation modification is caused in said transparent body which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation modification after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed;

d) a sampling device station containing the sampling device; and

e) means for deforming the locally transparent wall parts of the at least one measuring chamber in the sampling device in a controlled manner to reduce the volume of the at least one measuring chamber such that the sample of whole blood is substantially drained from the at least one measuring chamber, wherein the sampling device station of step (d) is arranged relative to the radiation source and the radiation detection means so that the radiation transmitted from the radiation source will pass through the at least one volume-reduced measuring chamber to the radiation detection means.

45. A method of photometric in vitro determination of the content of an analyte in a sample of whole blood, comprising the steps of:

a) transferring a sample of whole blood directly from in vivo locality to a sampling device, wherein the sampling device comprising;

at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis,

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable radiation modification is caused in said transparent body which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation modification after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed;

b) placing the sampling device in a sampling device station wherein the sampling device station is arranged relative to an optical system comprised of a radiation source and a means for detecting radiation such that the sampling device is located between the radiation source and the radiation detection means;

c) deforming the at least one measuring chamber of the sampling device in a controlled manner to reduce the volume of the at least one measuring chamber thereby substantially draining the sample of whole blood from the measuring chamber;

d) transmitting radiation from the radiation source through the deformed, substantially drained at least one measuring chamber to the radiation detector;

e) detecting the radiation transmitted in step d); and

f) determining the analyte content of the sample of whole blood from the radiation detected in step e).

46. A measuring chamber for photometric determination of the content of an analyte in a sample of whole blood, comprising:

two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber for photometric analysis,

said measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable radiation modification is caused in said transparent which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation modification after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed.

47. An analyzer for photometric determination of the content of an analyte in a sample of whole blood, comprising:

a) a radiation source;

b) means for detecting radiation transmitted from the radiation source;

c) at least one measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the two locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the at least one measuring chamber for photometric analysis,

said at least one measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable radiation modification is caused in said transparent body which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation modification after displacement of the whole blood sample from said at least one measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed

wherein the at least one measuring chamber is arranged relative to the radiation source and the radiation detection means so that the radiation transmitted from the radiation source will pass through the at least one measuring chamber to the radiation detection means; and

d) means for deforming at leas tone of the locally transparent wall parts of the at least one measuring chamber in a controlled manner to reduce the volume of the at least one measuring chamber such that the sample of whole blood is substantially drained from the at least one measuring chamber.

48. A method of photometric in vitro determination of the content of an analyte in a sample of whole blood, comprising the steps of:

a) transferring a sample of whole blood to a measuring chamber which has two locally transparent wall parts located opposite one another, at least one of the locally transparent wall parts being sufficiently deformable to facilitate displacement of the whole blood sample from the measuring chamber for photometric analysis,

said measuring chamber further including a transparent body disposed between the locally transparent wall parts, the transparent body being capable of selectively absorbing said analyte or reacting with said analyte such that upon contact of said analyte with said transparent body a detectable radiation modification is caused in said transparent body. which is dependent upon the concentration of said analyte in the whole blood sample, wherein the transparent body maintains said radiation transmission characteristic after displacement of the whole blood sample from said measuring chamber so that photometric analysis of said analyte in the absence of said whole blood sample can be performed;

the measuring chamber being arranged relative to an optical system comprised of a radiation source and a means for detecting radiation such that the measuring chamber is located between the radiation source and the radiation detection means;

b) deforming the measuring chamber in a controlled manner to reduce the volume of the measuring chamber thereby substantially draining the sample of whole blood from the measuring chamber;

c) transmitting radiation from the radiation source through the deformed, substantially drained measuring chamber to the radiation detector;

d) detecting the radiation transmitted in step c); and

e) determining the analyte content of the sample of whole blood from the radiation detected in step d).