Jet droplet device

• US 5,958,342 A
• Filed: 05/17/1996
• Issued: 09/28/1999
• Est. Priority Date: 05/17/1996
• Status: Expired due to Fees

• Current Assignee: Combion, Inc. (Incyte Corporation)
• Original Assignee: Incyte Pharmaceuticals, Inc.
• Inventors: Baldeschwieler, John, Gamble, Ronald C., Theriault, Thomas P.
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US08/649,535
• Time in Patent Office: 1,229 Days
• Field of Search: 422/100, 422/65, 347/68-72
• US Class Current: 422/507
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00531 essentially square
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2001/282 with mapping; Identification of areas; Spatial correlated pattern
• CPC Class Codes: G01N 2035/1041 Ink-jet like dispensers

Abstract

Devices and methods are provided for precise production of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Claims

1. A pulse jetting device providing droplets capable of providing arrays of spots of less than 500 microliters from center to center with substantially no contamination of one spot with another, said device comprising:

a housing comprising a first constricted opening at one end and a second opening at the other end;

a capillary comprising a dispensing orifice having a diameter in the range of about 10 to 100 microns and a volume capacity in the range of about 1 to 10 microliters and extending a portion of the length of said housing with said dispensing orifice extending through said first opening;

proximal to said dispensing orifice, a piezoelectric transducer mounted concentrically on said capillary and affixed to said capillary, wherein the walls of said capillary move with the movement of said transducer;

proximal to said second end and extending at least about 40% of the length of said capillary a capillary casing affixed to said capillary, with said casing filling the space between said capillary and the inner wall of said housing;

in liquid transfer relationship with said second end and extending into said housing, a receptacle for a sample, wherein the compositions of said receptacle and capillary are selected so that upon contact of said sample with said capillary, said sample fills said capillary by capillary action;

a lid having a plurality of conduits, each conduit being valved;

means for hermetically sealing said lid to said receptacle; and

means for connecting said piezoelectric transducer to a control system.

2. A pulse jetting device according to claim 1, wherein said capillary has walls of from 0.10 to 0.40 mm in thickness.

3. A pulse jetting device according to claim 1, wherein said sample receptacle has volume ranging from about 5 to 50 μ

l.

4. A pulse jetting device according to claim 1, wherein said capillary is hydrophilic and said receptacle is hydrophobic.

5. A pulse jetting device according to claim 4, wherein said capillary is glass and said receptacle is nylon.

6. A spot array forming system comprising:

a plurality of pulse jetting devices according to claim 1;

means for moving at least one pulse jetting device from a reserve position to an active position for dispensing droplets;

a substrate holding device for holding a substrate in position to receive said droplets;

means for accurately moving said at least one pulse jetting device and said substrate holding device in relation to each other for precisely positioning spots on said substrate in a spot array.

7. A spot array forming system according to claim 6, wherein said system forms adjacent spots that are less than 500 microns from center to center and at least 15 microns from border to border.

8. A spot array forming system according to claim 6, wherein said means for accurately moving comprises an x-y raster servomechanism.

9. A spot array forming system according to claim 6, wherein said means for accurately moving is a linear servomechanism and said substrate holding device comprises a rotating platform for supporting said substrate.

10. A spot array forming system according to claim 6, wherein said system forms adjacent spots with a center-to-center separation of not more than 100 microns.

11. A spot array forming system according to claim 6, wherein a plurality of jetting devices are held together to move as a group.

12. A pulse jetting device providing droplets capable of providing arrays of spots of less than 500 microns from center to center with substantially no contamination of one spot with another, said device comprising:

a housing comprising a first constricted opening at the lower end and a second opening at the top end;

a glass capillary comprising a dispensing orifice having a diameter in the range of about 10 to 100 microns and a volume capacity in the range of about 1 to 10 microliters and extending a portion of the length of said housing with said dispensing orifice extending through said first opening;

proximal to said dispensing orifice, a piezoelectric transducer mounted concentrically on said capillary and affixed to said capillary, wherein the walls of said capillary move with the movement of said transducer;

proximal to said second end and extending at least about 40% of the length of said capillary a capillary casing affixed to said capillary and threaded into said housing, with said casing filling the space between said capillary and the inner wall of said housing, the top of said casing being flush with said housing and being below the top of said housing;

in liquid transfer relationship with said second end and extending into said housing, a sample receptacle threaded into said housing and locking said casing in said housing, wherein the composition of said receptacle is hydrophobic, so that upon contact of a polar sample with said capillary, said polar sample fills said capillary by capillary action;

a lid having a plurality of conduits, each conduit being valved;

means for hermetically sealing said lid to said receptacle; and

means for connecting said piezoelectric transducer to a control system.

13. A pulse jetting device according to claim 12, wherein said dispensing orifice has a diameter in the range of 10 to 80μ

.

14. A pulse jetting device according to claim 12, wherein said capillary has walls of from 0.10 to 0.40 mm in thickness.

15. A pulse jetting device according to claim 12, wherein said sample receptacle has volume ranging from about 5 to 50 μ

l.

16. A pulse jetting device according to claim 12, wherein the length of said capillary is in the range of 1.5 to 4 cm.

17. A spot array forming system comprising:

a plurality of pulse jetting devices according to claim 12;

means for moving at least one pulse jetting device from a reserve position to an active position for dispensing droplets;

a substrate holding device for holding a substrate in position to receive said droplets; and

means for accurately moving said at least one pulse jetting device and said substrate holding device in relation to each other for precisely positioning spots on said substrate in a spot array.