Solid-state optical assay imaging apparatus

• US 4,737,464 A
• Filed: 09/26/1985
• Issued: 04/12/1988
• Est. Priority Date: 09/26/1985
• Status: Expired due to Fees

• Current Assignee: Molecular Devices
• Original Assignee: Molecular Devices
• Inventors: Briggs, Jonathan, Parce, John W., McConnell, Harden M.
• Primary Examiner(s): Marcus, Michael S.
• Application Number:
  US06/780,485
• Time in Patent Office: 929 Days
• Field of Search: 422/63, 422/65, 422/67, 422/72, 422/73, 422/68, 436/47, 436/43, 436/805, 436/807, 356/127, 356/246, 358/213
• US Class Current: 436/43
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/272 for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
• 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 2201/0461 Simultaneous, e.g. video imaging
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

An apparatus for determining a characteristic of a signal modulating component related to an analyte of interest at an assay site by measuring light modulated by the component. A light source uniformly illuminates the assay site and a reference site. The light is directed from the sites onto a group of memory cells on the surface of a random access memory. The memory cells will decay from a logical 1 to a logical 0 due to the light over a period of time which is a function of the intensity of the light and the reference voltage of the memory cells marking the difference between a 1 and a 0. The digital state of each of the memory cells in the group is measured a predetermined exposure time. The measured states of a group of memory cells corresponding to the assay site are compared to the memory cell states for a reference group. The measured states are then analyzed to determine a characteristic of the analyte.

Claims

1. An apparatus for determining a characteristic of an analyte in a sample by measuring the light transmitted from an assay site in relation to the amount of signal modulating component present at said assay site, wherein the amount of said component is related to the presence of said analyte in said sample, said apparatus comprising:

means for irradiating an assay site and a standard reference site with light while correcting for any nonuniformity in the light;

a dynamic random access memory;

means for directing light from said sites onto a first and a second group of memory cells, respectively, of said dynamic random access memory;

means for exposing said memory cells to said directed light for a predetermined period of time;

means for measuring the states of said memory cells after said exposure of said group of memory cells;

means for comparing said measured states of said first group and said second group; and

means for analyzing said compared states to determine said characteristic of said analyte.

2. The apparatus of claim 1 further comprising means for measuring the state of said memory cells at a plurality of different times to produce a gray scale.

3. The apparatus of claim 1 further comprising means for varying a reference voltage of said memory cells so that the sensitivity to light of said memory cells is varied.

4. The apparatus of claim 3 further comprising means for adjusting said reference voltage to a plurality of levels and means for measuring the states of said memory cells at each of said levels to produce a gray scale.

5. The apparatus of claim 1 further comprising means for focussing said light from said assay and reference sites onto said group of memory cells.

6. The apparatus of claim 1 further comprising means for irradiating a plurality of assay sites simultaneously and means for directing light from each said assay site to a different one of a plurality of groups of memory cells of said dynamic random access memory.

7. The apparatus of claim 1 further comprising means for changing the memory cells composing said group so that light from said assay site is substantially centered in said group.

8. An apparatus for determining a characteristic of a plurality of analytes in a plurality of samples by measuring the light transmitted from a plurality of assay sites on a solid support in relation to the amount of signal modulating component present at each said assay site, wherein the amount of said component is related to the presence of analyte in a sample, said apparatus comprising:

a light source for uniformly directing light to a plurality of assay sites and to a reference site;

a dynamic random access memory having a plurality of memory cells, said memory having an exposed surface covered by a light-transmitting non-reflective plate;

a lens for focussing light from each said site onto a separate block of said memory cells;

a sequencer for sequentially reading said memory cells after a predetermined exposure time;

means for comparing the states of said memory cells for each said block;

means for comparing said measured states for a reference site block to each of the other blocks; and

means for analyzing said compared states to determine said characteristic of said analytes.

9. The apparatus of claim 8 further comprising a computer for controlling the operation of said apparatus and analyzing the states of said memory cells.

10. The apparatus of claim 8 further comprising a plurality of lenses arranged to focus an image from a single site onto a plurality of blocks of memory cells on said dynamic random access memory and a plurality of filters, each filter being arranged to filter an image projected by one of said lenses onto one of said blocks of memory cells.

11. The apparatus of claim 8 further comprising means for applying reagents to said sites on said solid support.

12. A method for determining a characteristic of an analyte in a sample, said method comprising the steps of:

irradiating an assay site and a standard reference site with light while correcting for any non-uniformity in the light;

directing light from said sites onto a first and a second group of memory cells, respectively, of a dynamic random access memory;

exposing said memory cells to said directed light for a predetermined period of time;

measuring the states of said memory cells after said exposure of said group of memory cells;

comparing said measured states of said first group and said second group; and

analyzing said compared states to determined said characteristic of said analyte.

13. The method of claim 12 wherein said step for measuring the state of said memory cells is performed at a plurality of different times to produce a gray scale.