Apparatus and method for transferring small volumes of substances

• US 6,916,447 B2
• Filed: 12/12/2001
• Issued: 07/12/2005
• Est. Priority Date: 04/16/1999
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Kowallis, Reid Burton
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US10/016,979
• Publication Number:
  US 20020041829A1
• Time in Patent Office: 1,308 Days
• Field of Search: 422/63, 422/65, 422/66, 422/67, 422/99, 422/100, 422/102, 422/104, 436/43, 436/44, 436/46, 436/50, 436/54, 436/174, 436/180
• US Class Current: 422/66
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 35/00009 provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/10 Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25625 Dilution
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides a method and apparatus for dispensing small volumes of selected substances, such as biological reagents or samples, onto substrates. According to one general embodiment, a plurality of spaced, tandemly-arranged substrates are advanced, e.g., by way of a conveyor, along a transport pathway extending over a reagent-supply location, such as a reservoir supported at a fixed position in a base. From a position over the reagent-supply location and the pathway, a reagent-transfer instrument, or tip, is extended along an axis through an intervening region, e.g., an opening defined by a surface of the conveyor, separating an adjacent pair of advancing substrates to contact reagent held at the reagent-supply location. The reagent-transfer instrument is then withdrawn, along with a portion of such reagent, through the intervening region to a position above the transport pathway. Once the conveyor has advanced a selected substrate, upstream of the intervening region, to a position aligned with the axis of the reagent-transfer instrument, a selected amount of reagent is transferred from the instrument onto a selected site of the substrate. Advantageously, the apparatus and method are readily adaptable for the production of micro-arrays having a great number of closely spaced spots.

Claims

1. A spotting system, comprising:

a base including one or more areas adapted to hold one or more reagents;

a conveyor positioned over said base, said conveyor including a surface defining (i) a plurality of substrate-support areas for holding or containing substrates to be spotted with said one or more reagents, and (ii) a plurality of openings permitting access to said one or more base areas;

a transfer head which is movable along an axis for obtaining reagents from the base through said openings in the conveyor surface; and

one or more controllers for controlling the movement of the conveyor and the transfer head.

2. The system of claim 1, wherein an elongate flexible belt defines said conveyor.

3. The system of claim 1, which further includes one or more additional transfer heads disposed at spaced positions along said conveyor.

4. The system of claim 3, wherein at least one of said transfer heads is laterally offset from the other transfer heads.

5. The system of claim 3, wherein a plurality of transfer heads are disposed in a row extending laterally or obliquely across the conveyor surface at one or more of said spaced positions.

6. A reagent-manipulation apparatus, comprising:

a conveyor including a surface with a plurality of spaced, tandemly-arranged substrate-support regions, each adapted to support a substrate, said conveyor surface defining an opening between each adjacent pair of substrate-support regions;

a base located under the conveyor and adapted to hold one or more reagents;

a transfer head being mounted for movement along an axis, between a raised position at which the head is disposed above the conveyor surface and a lowered position whereat the head can contact said one or more reagents; and

one or more controllers for controlling the movement of the conveyor and transfer head.

7. The system of claim 6, wherein an elongate flexible belt defines said conveyor.

8. The system of claim 6, which further includes one or more additional transfer heads disposed at spaced positions along said conveyor.

9. The system of claim 8, wherein at least one of said transfer heads is laterally offset from the other transfer heads.

10. The system of claim 8, wherein a plurality of transfer heads are disposed in a row extending laterally or obliquely across the conveyor surface at one or more of said spaced positions.

11. A method for accessing a reagent held at a reagent-supply location, under a plurality of spaced substrates, comprising:

(i) advancing said plurality of spaced substrates along a transport pathway extending over said reagent-supply location; and

(ii) from a position over said reagent-supply location and said pathway, extending a reagent-transfer instrument through an intervening region separating an adjacent pair of said substrates to contact said reagent held at said reagent-supply location.