Apparatus for improved luminescence assays using particle concentration and chemiluminescence detection

• US 5,798,083 A
• Filed: 06/06/1995
• Issued: 08/25/1998
• Est. Priority Date: 11/03/1988
• Status: Expired due to Fees

• Current Assignee: BioVeris Corporation (Roche Holding AG)
• Original Assignee: IGEN International, Inc. (Roche Holding AG)
• Inventors: Shah, Haresh P., Massey, Richard J., Blackburn, Gary F., Wilkins, Elizabeth W.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/469,464
• Time in Patent Office: 1,176 Days
• Field of Search: 422/52, 436/172, 356/244-246, 73/864, 252/363, 252/366
• US Class Current: 422/52
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/103 luminescence
• CPC Class Codes: C12Q 2563/131 the label being a member of a cognate binding pair, i.e. extends to antibodies, haptens, avidin
• CPC Class Codes: C12Q 2565/102 Multiple non-interacting labels
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 21/69 specially adapted for fluids , e.g. molten metal
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2458/30 Electrochemically active labels
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/585 with a particulate label, e.g. coloured latex

Abstract

What is described are methods and apparatus for performing a binding assay for an analyte of interest present in a sample. The methods include the steps of: forming a composition containing the sample, an assay-performance-substance which contains a component linked to a label compound capable of chemiluminescing when triggered, and a plurality of particles capable of specifically binding with the analyte and/or the assay-performance-substance; incubating the composition to form a complex which includes a particle and the labeled component; collecting the complex in a collection zone; introducing into the collection zone a trigger capable of triggering the label such that the label luminesces; and measuring the emitted luminescence to measure the presence of the analyte of interest in the sample.

Claims

1. An apparatus for measurement of an analyte of interest based upon measurement of chemiluminescence comprising:

(a) a cell consisting essentially of a sample volume having a vertical columnar zones, inlet means and outlet means for generating a magnetic field positioned proximate to a single collection zone, said collection zone being below a substantial volume of said cell and said columnar zone, and said field being sufficient to collect said analyte of interest at said collection zone when any such analyte of interest is bound directly or indirectly to a magnetic particle; and

(b) means to measure the chemiluminescence generated at the collection zone.

2. An apparatus as recited in claim 1, wherein said means to measure the chemiluminescence is a photomultiplier tube.

3. An apparatus as recited in claim 1, further comprising a means for reflecting chemiluminescence generated at the collection zone onto said means to measure the chemiluminescence.

4. An apparatus as recited in claims 1, wherein said means for generating said magnetic field is a permanent magnet.

5. An apparatus as recited in claim 1, wherein said means for generating said magnetic field is an electromagnet.

6. An apparatus as recited in claim 1, further comprising a housing enclosing said cell and shielding said means to measure the chemiluminescence from external light during chemiluminescent measurements.

7. An apparatus as recited in claim 1, further comprising a shutter mechanism provided between said cell and said means to measure the chemiluminescence.

8. An apparatus as recited in claim 7, wherein said shutter mechanism is controllably operated to open only so far as to expose the means to measure the chemiluminescence from the collection zone in the cell during chemiluminescence measurement periods.

9. An apparatus as recited in claim 1, further comprising a pump suitable for providing fluid transport to, through and from said cell.

10. An apparatus as recited in claim 9, wherein said pump is a peristatic pump.

11. An apparatus as recited in claim 9, wherein said pump is a positive displacement pump.

12. An apparatus as recited in claim 1, wherein said means to measure chemiluminescence does so by directly measuring chemiluminescence emitted at the collection zone.

13. An apparatus as recited in claim 12, further comprising a shutter mechanism provided between said cell and said means to measure the chemiluminescence.

14. An apparatus as recited in claim 12, wherein said shutter mechanism is controllably operated to open only so far as to expose the means to measure the chemiluminescence from the collection zone in the cell during chemiluminescence measurement periods.

15. An apparatus as recited in claim 12, further comprising a means for reflecting chemiluminescence generated at the collection zone onto said means to measure the chemiluminescence.

16. An apparatus as recited in claim 12, further comprising a housing enclosing said cell and shielding said means to measure the chemiluminescence from external light during chemiluminescent measurements.

17. An apparatus as recited in claim 12, wherein said means to measure the chemiluminescence is a photomultiplier tube.

18. An apparatus as recited in claim 12, further comprising a pump suitable for providing fluid transport to, through and from said cell.

19. An apparatus as recited in claim 18, wherein said pump is a peristatic pump.

20. An apparatus as recited in claim 18, wherein said pump is a positive displacement pump.

21. An assay apparatus for measurement of an analyte of interest based upon measurement of chemiluminescence comprising:

(a) a cell consisting essentially of a sample volume having inlet means and outlet means and a single collection zone;

(b) means for generating a magnetic field at said collection zone, wherein said means for generating said magnetic field is positioned proximate to said cell and said field is sufficient to collect said analyte at said collection zone when any such analyte of interest is bound directly or indirectly to a magnetic particle; and

(c) means to measure the chemiluminescence generated at the collection zone.

22. An apparatus as recited in claim 21, wherein said means to measure chemiluminescence does so by directly measuring chemiluminescence emitted at the collection zone.