Disposable cartridge for an assay of a biological sample

• US 5,627,041 A
• Filed: 09/02/1994
• Issued: 05/06/1997
• Est. Priority Date: 09/02/1994
• Status: Expired due to Fees

• Current Assignee: Biometric Imaging, Inc. (Becton, Dickinson & Co)
• Original Assignee: Biometric Imaging, Inc. (Becton, Dickinson & Co)
• Inventors: Shartle, Robert J.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/300,360
• Time in Patent Office: 977 Days
• Field of Search: 436/536, 436/70, 436/172, 436/179, 436/45, 436/809, 436/165, 436/514, 422/50, 422/68.1, 422/72, 422/82.06, 422/82.07, 422/82.08, 422/58, 435/287.1, 435/287.2, 435/287.6, 435/288.4, 435/288.5, 435/288.7, 435/810, 435/7.24, 435/808, 435/973
• US Class Current: 435/7.24
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 25/422 between stacked plates, e.g. grooved or perforated plates
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/7172 using capillary forces
• CPC Class Codes: B01F 35/71725 using centrifugal forces
• CPC Class Codes: B01F 35/7173 using gravity, e.g. from a hopper
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 21/07 Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/111666 : Utilizing a centrifuge or compartmented rotor
• CPC Class Codes: Y10T 436/25625 : Dilution

Abstract

A cartridge is provided to present a biological sample for analysis by an imaging instrument. The cartridge of the invention utilizes a series of channels, capillaries, reservoirs and stop junctions to precisely move a sample, reagent and diluent through the cartridge as a function of the sum of capillary, gravitational and low centrifugal forces. The operator applies a precise amount of sample to the cartridge; therefore, the cartridge fluidics need not meter the sample prior to dilution. A practical and cost effective cartridge and assay process is disclosed which overcomes many of the limitations of the prior art. Such a cartridge is especially useful with fixed volume assays which permit low centrifugal accelerations to move the fluids within the cartridge.

Claims

1. A fluidics circuit which permits fluid flow at low centrifugal accelerations, the fluidics circuit comprising:

radial means for delivering fluid, said radial means including an inlet and an outlet having a radial position outward from the inlet, said radial means further including a fluid passage configured to prohibit fluid flow through the outlet of said radial means; and

receiving means for providing a stop junction in fluid communication with the outlet of said radial means, wherein the radial position of the inlet and the outlet of said radial means are selected such that fluid will flow through the outlet when a low level of centrifugal acceleration having a range of one to one hundred meters per second per second is applied to said radial means.

2. A fluidics circuit which permits fluid flow at low centrifugal accelerations, the fluidics circuit comprising:

radial means for delivering fluid, said radial means including an inlet and an outlet having a radial position outward from the inlet, said radial means further including a fluid passage configured to allow fluid flow through the outlet of said radial means;

a stop flow capillary including an inlet in fluid communication with the outlet of said radial means, said stop flow capillary further including an outlet and a fluid passage configured to prohibit fluid flow through the outlet of said stop flow capillary; and

receiving means for providing a stop junction in fluid communication with the outlet of said stop flow capillary, wherein the radial position of the inlet and the outlet of said radial means are selected such that fluid will flow through said stop flow capillary when a low level of centrifugal acceleration having a range of one to one hundred meters per second per second is applied to said radial means and said stop flow capillary.

3. The fluidics circuit of claim 2, wherein the low level of centrifugal acceleration applied to said radial means and said stop flow capillary is twenty meters per second per second.

4. The fluidics circuit of claim 2, wherein the radial position of the outlet of said radial means is at least one millimeter from the inlet of said radial height means.

5. The fluidics circuit of claim 4, wherein the radial position of the outlet of said radial means is less than one hundred-fifty millimeters from the inlet of said radial height means.

6. The fluidics circuit of claim 2, wherein the radial position of the outlet of said radial means is twenty-five millimeters from the inlet of said radial means.

7. The fluidics circuit of claim 2, wherein a column of fluid containing a suspended particle having a diameter is disposed between the inlet and the outlet of said radial means, and wherein the fluid passage of said stop flow capillary is configured with a cross-sectional area so that the suspended particle will not migrate a distance greater than one thousand times the diameter of the suspended particle when the column of fluid is subjected to the low level of centrifugal acceleration.

8. A fluidics circuit which permits fluid flow at low centrifugal accelerations, the fluidics circuit comprising:

a first capillary including an inlet and an outlet having a radial position outward from the inlet, said first capillary including a fluid passage having a capillary back pressure which allows fluid flow through the outlet of said first capillary;

a second capillary including an inlet in fluid communication with the outlet of said first capillary, said second capillary further including an outlet and a fluid passage having a capillary back pressure which prohibits fluid flow through the outlet of said second capillary; and

a chamber providing a stop junction in fluid communication with the outlet of said second capillary, wherein the radial position of the inlet and the outlet of said first capillary are selected such that fluid will flow through said second capillary when a low level of centrifugal acceleration having a range of one to one hundred meters per second per second is applied to said first capillary and said second capillary.

9. An assay cartridge comprising:

a body;

a first reservoir configured in said body to receive a fluid sample;

a first capillary configured in said body so as to have a first end in fluid communication with said first reservoir;

a first stop junction configured in said body and in fluid communication with a second end of said first capillary, said first stop junction including a second capillary having a capillary back pressure which prohibits fluid flow from said first capillary; and

a second reservoir configured in said body and in fluid communication with said first stop junction, wherein the fluid sample flows from said first reservoir, through said first capillary and through said first stop junction and into said second reservoir upon application to said body of a first low centrifugal acceleration having a range of one to one hundred meters per second per second.

10. The cartridge of claim 9, further comprising:

a third reservoir configured in said body to retain a glass ampule having a diluent;

a third capillary configured in said body and having a first end in fluid communication with said third reservoir; and

a second stop junction configured in said body and in fluid communication with a second end of said third capillary and said second reservoir, wherein after said glass ampule is broken the diluent flows from said third reservoir to said second reservoir upon application to said body of a second low centrifugal acceleration having a range of one to one hundred meters per second per second.

11. The cartridge of claim 10, further comprising:

a scan capillary configured at least partially in said body; and

a third stop junction configured in said body and in fluid communication with said second reservoir and with said scan capillary, wherein said third stop junction prevents the fluid sample and the diluent from leaving said second reservoir when the second low centrifugal acceleration is applied to said body, and wherein a portion of the fluid sample and diluent flows from said second reservoir into said scan capillary upon application to said body of a third low centrifugal acceleration greater than the second low centrifugal acceleration and having a range of one to one hundred meters per second per second.

12. The cartridge of claim 11, wherein said body comprises a first plate, a second plate and a third plate, said first reservoir being configured in the first plate and the second plate, said second reservoir being configured in the second plate and the third plate, and said third reservoir being configured in the first plate, the second plate and the third plate.

13. The cartridge of claim 11, wherein said scan capillary has a rectangular internal cross-section.

14. The cartridge of claim 9, wherein said first reservoir contains at least one antibody tagged with a fluorescent dye.

15. The cartridge of claim 9, wherein said body is substantially shaped in the form of a triangle.

16. The cartridge of claim 9, wherein said first reservoir is configured to receive variable amounts of a sample.