Analytical cartridge and system for detecting analytes in liquid samples

• US 5,223,219 A
• Filed: 04/10/1992
• Issued: 06/29/1993
• Est. Priority Date: 04/10/1992
• Status: Expired due to Term

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Biotrack, Inc. (Novartis Ag)
• Inventors: Subramanian, Kumar, Voss, Fred, Saltman, Marina, Sterling, Bernhard B., Sugarman, Jeffrey
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): BHAT, NINA NMN
• Application Number:
  US07/867,162
• Time in Patent Office: 445 Days
• Field of Search: 422/55, 422/58, 422/82.09, 422/73, 422/102, 422/119, 422/82, 210/451, 210/505
• US Class Current: 422/404
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/082 Handling hazardous material
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/035 Supports for sample drops
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: Y10S 366/01 Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway

Abstract

A diagnosis system, which comprises a monitor, comprising a detector providing multiple reflectance readings in an array of individual locations, registering an analytical cartridge in the monitor at a fixed location and orientation relative to the array, and determines and displays analytical results from reflectance readings; and an analytical cartridge, comprising a liquid impervious housing, a sample application site in the housing located outside the monitor when the cartridge is registered in the monitor by the means for registering, one or more reflectance reading sites in the housing that register with one or more of the locations in the array, a capillary pathway in the housing leading from the sample application site to each of the reflectance reading sites, and a reflectance matrix located in at least one of the reflectance reading sites. In some embodiments of the invention, control features that optimize accuracy of measurement by controlling when and if sample reaches reflectance reading sites and by drawing excess sample away from undesirable locations in the cartridge are present. One control element balances the liquid-holding capacities of the application site, the sample-transporting capillary passageway that leads to the reflectance reading site, and the porous matrices from which the reflectance reading will be made, so that excess sample is excluded from entry into the cartridge while sample volumes that are below the minimum necessary for accurate operation do not reach the matrix, thereby avoiding false readings.

Claims

1. An analytical cartridge, comprising:

a. a liquid impervious housing,

b. a sample application site comprising a cavity located in an exterior surface of said housing and having an application-site liquid-holding capacity,

c. a reflectance reading site comprising a chamber in said housing,

d. means for venting said chamber to atmosphere,

e. a sample-transporting capillary passageway in said housing connecting said sample application site to said reflectance reading site and having a sample-transport liquid-holding capacity, and

f. a porous matrix located in said reflectance reading site and having a porous-matrix liquid-holding capacity,

wherein said sample-transport capacity is greater than said porous-matrix capacity and said application-site capacity is less than the sum of said sample-transport capacity and said porous-matrix capacity.

2. The analytical cartridge of claim 1, wherein said sample-transporting capillary passageway comprises wall means for subjecting said sample to equal motive and retarding forces at locations of leading and trailing meniscuses when a sample having a volume equal to said porous-matrix capacity enters said capillary passageway from said application site, whereby said sample is prevented from flowing into said matrix, the locations of said leading and trailing meniscuses for said volume of sample equal to said matrix capacity being identified as a leading equal-volume location and a trailing equal-volume location, respectively.

3. The analytical cartridge of claim 2, wherein said capillary passageway and said application site are connected at an application-site junction and said capillary passageway comprises wall means for providing a radius of curvature at said junction for a trailing sample meniscus located at said junction equal to a radius of curvature for a leading sample meniscus located at said leading equal-volume location.

4. The analytical cartridge of claim 2, wherein said capillary passageway has equal cross-sectional dimensions at said equal-volume locations.

5. The analytical cartridge of claim 2, wherein said capillary passageway has different cross-sectional dimensions at said equal-volume locations, but said equal forces are provided by walls of said capillary having different surface energies or gravitational potentials at said equal-volume locations.

6. The analytical cartridge of claim 1, wherein said cartridge comprises directing means for causing sample applied near said application site to flow into said application site.

7. The analytical cartridge of claim 6, wherein said directing means comprises a surface substantially surrounding said application site and sloping toward said application site.

8. The analytical cartridge of claim 6, wherein said directing means further comprises means for excluding sample in excess of said application-site capacity from said application site.

9. The analytical cartridge of claim 8, wherein said directing means site comprises a surface substantially surrounding said application and sloping toward said application site and said means for excluding sample comprises a slot in an upper region of said surface.

10. The analytical cartridge of claim 2, wherein said cartridge further comprises an overflow capillary passageway connected to said sample-transporting capillary passageway at an overflow junction.

11. The analytical cartridge of claim 10, wherein said overflow junction is located in said sample-transporting capillary passageway beyond said leading equal-volume location.

12. The analytical cartridge of claim 11, wherein said overflow capillary passageway comprises wall means for forming a meniscus that exerts a capillary force less than that present in said sample-transporting capillary passageway or said porous matrix when a sample is present in said overflow caapillary passageway and in said sample-transporting capillary passageway or porous matrix.

13. The analytical cartridge of claim 10, wherein said overflow junction is located in said sample-transporting capillary passageway before said leading equal-volume location.

14. The analytical cartridge of claim 13, wherein said overflow capillary passageway comprises wall means for forming a meniscus that exerts a capillary force less than that present in said sample-transporting capillary passageway when a sample is present in said overflow caapillary passageway and in said sample-transporting capillary passageway.

15. The analytical cartridge of claim 1, wherein (1) said cartidge comprises multiple reflectance reading sites containing multiple reflectance-reading matrices, said muliple matrices jointly having said porous-matrix capacity, and (2) said sample-transporting capillary passageway comprises (a) branch capillaries leading to each of said sites from one or more branch sites in said sample-transporting capillary passageway and (b) an initial trunk capillary connecting said sample application site to a first branch site of said branch sites in said sample-transporting capillary passageway.

16. The analytical cartridge of claim 15, wherein said trunk capillary has a trunk liquid-holding capacity larger than said porous-matrix capacity.

17. The analytical cartridge of claim 16, wherein said branch capillaries each have wall means for providing a motive capillary force larger than retarding capillary force in said trunk capillary when a sample is present in said sample-transport capillary and said sample has a leading meniscus in one of said branch capillaries and a trailing meniscus in said trunk capillary.

18. The analytical cartridge of claim 17, wherein said trunk capillary comprises wall means for subjecting said sample to equal motive and retarding forces at locations of leading and trailing meniscuses when a sample having a volume equal to said porous-matrix capacity enters said truck capillary from said application site, whereby said sample is prevented from flowing into said branch capillaries, the locations of said leading and trailing meniscuses for said volume of sample equal to said matrix capacity being identified as a leading equal-volume location and a trailing equal-volume location, respectively.

19. The analytical cartridge of claim 1, wherein said means for venting comprises an opening in an upper surface of said housing at said chamber, whereby a surface of said reflectance matrix is exposed to external irradiation and reflectance through said opening.

20. The analytical cartridge of claim 19, wherein said opening comprises a stop-flow junction below said upper surface.

21. The analytical cartridge of claim 20, wherein said opening is circular and said stop-flow junction comprises a ledge having an edge with an interior angle of 90°

or less projecting into said opening.

22. A diagnosis system, which comprises:

a. a monitor, comprising;

i. means for detecting multiple reflectance readings in an array of individual locations,

ii. means for registering an analytical cartridge at a fixed location and orientation relative to said array in an interior space of said monitor, and

iii. means for determining and displaying analytical results from reflectance readings obtained at individual locations in said array; and

b. a first analytical cartridge, comprising;

i. a liquid impervious housing,

ii. a sample application site in said housing at a location that is outside said monitor when said cartridge is registered in said monitor by said means for registering,

iii. one or more reflectance reading sites positioned in said housing to register with one or more of said locations in said array when said cartridge is registered in said monitor,

iv. a capillary pathway in said housing leading from said sample application site to each of said one or more reflectance reading sites, and

v. a reflectance matrix located in at least one of said reflectance reading sites.

23. The system of claim 22, wherein multiple reflectance reading sites are present in said cartridge.

24. The system of claim 23, wherein said system further comprises a second analytical cartridge capable of measuring at least one analyte not in common with analytes measured by said first cartridge.

25. The system of claim 24, wherein said second analytical cartridge comprises at least one reflectance reading site at a location in said array different from reflectance reading sites utilized by said first analytical cartridge.

26. The system of claim 22, wherein said monitor further comprises means for detecting and identifying said analytical cartridge when inserted into said monitor and said cartridge further comprises information encoded on said cartridge whereby said means for detecting and identifying said analytical cartridge identifies said cartridge as belonging to a predetermined cartridge type recognized by said monitor when said cartridge is inserted in said monitor.

27. The system of claim 26, wherein said second analytical cartridge comprises at least one capillary passageway different from capillary passageways utilized by said first analytical cartridge.

28. The system of claim 22, wherein said housing comprises a capillary tree connecting a single application site to a plurality of assay stacks, wherein said capillary tree comprises an initial capillary passageway with a first cross-sectional area and a plurality of branch capillary passageways connecting said initial capillary passageway to said assay stacks, either directly or through further branch capillary passageways, wherein each of said branch capillaries in a pathway connecting said trunk capillary to one of said assay stacks is smaller than said trunk capillary and any preceding branch capillary in said connection.

29. The system of claim 22, wherein said reflectance reading sites are present in an array accessible on one flat surface of said housing.

30. An analytical cartridge, comprising:

a. a liquid impervious housing,

b. a sample application site comprising a cavity located in an exterior surface of said housing,

c. a reflectance reading site comprising a chamber in said housing,

d. a sample-transporting capillary passageway in said housing connecting said sample application site to said reflectance reading site,

e. a porous matrix located in said reflectance reading site, and

f. an opening in said housing at said chamber, whereby a surface of said reflectance matrix is exposed to potential external irradiation and reflectance through said opening, comprises a stop-flow junction.

31. The analytical cartridge of claim 30, wherein said opening is circular and said stop-flow junction comprises a ledge having an edge with an interior angle of 90°

or less.

32. The analytical cartridge of claim 31, wherein said opening is circular and said stop-flow junction occurs at junction in said opening where said opening changes from a proximal smaller diameter to a distal larger diameter, proximal and distal locations in said opening being relative to said surface of said reflectance matrix.

33. In a diagnostic cartridge comprising a four-walled interior capillary passageway that supplies an analytical liquid to a chamber containing a porous, disk-shaped matrix having a diameter D greater than its height and a bottom surface substantially in contact with the floor of said chamber, an improvement which comprises:

said four-walled capillary passageway located so that it enters said chamber at a lower edge of said disk,

one or more three-walled capillary passageways provided in said floor connected to the entrance location of said four-wall capillary passageway into said chamber, wherein no point on the bottom surface of said disk is further than one-half D from at least one point of said three-walled capillary passageways.

34. The cartridge of claim 33, wherein said four-walled capillary passageway enters an empty space beneath said floor, said space having a secondary floor that slopes upward to a central location of said matrix and a three-walled capillary channel is present in said secondary floor, whereby sample entering said space is drawn upward by said three-walled capillary channel to said matrix.