Apparatus and method for sample delivery

• US 6,605,475 B1
• Filed: 04/16/1999
• Issued: 08/12/2003
• Est. Priority Date: 04/16/1999
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Perspective Biosystems, Inc.
• Inventors: Yao, Xian-Wei, Taylor, Todd A., Carson, William W.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R
• Application Number:
  US09/293,314
• Time in Patent Office: 1,579 Days
• Field of Search: 422/58, 422/59, 422/68.1, 422/157, 422/146, 422/147, 422/164, 422/172, 422/99, 422/173, 436/180, 204/265, 204/271, 204/274, 374/20, 374/39, 374/43, 374/54, 219/521, 392/465-466, 392/480-482, 392/484, 165/110
• US Class Current: 436/180
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Apparatus and methods have been developed to deliver automatically a sample to a reaction vessel, an analytical device or any location where sample introduction or deposition is desired. A sample delivery system of the invention generally includes a housing defining a channel, e.g., a capillary, and a volume controller, which is a temperature control device, in thermal communication with the channel. The channel preferably is closed at one end, and contains an opening for introduction of a sample. The closed end of the channel is associated thermally with the temperature control device. The temperature control device heats and cools a thermally expandable fluid in the channel which controls movement of a sample into, within and out of the channel.

Claims

1. A thermally-controlled sample delivery system comprising:

a housing defining a channel, the channel comprising an open end and a closed end;

an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both;

a thermally expandable fluid disposed within the channel; and

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally expandable fluid disposed within the channel,

wherein the volume controller is used to transport a sample in the channel.

2. A thermally-controlled sample delivery system comprising:

a housing defining a channel, the channel comprising an open end and a closed end;

at least one chemical reagent that is capable of interacting with a sample or a component of a sample disposed within the channel;

an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both;

a thermally expandable fluid disposed within the channel; and

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally expandable fluid disposed within the channel,

wherein the volume controller is used to transport a sample in the channel.

3. The thermally-controlled sample delivery system of claim 2 wherein the chemical reagent is immobilized within the channel.

4. The thermally-controlled sample delivery system of claim 2 wherein the chemical reagent is selected from the group consisting of an oligonucleotide, a peptide nucleic acid, a binding protein, an enzyme, a substrate, a ligand, a receptor, an antibody and an antigen.

5. The thermally-controlled sample delivery system of claim 2 further comprising a stabilizer for the chemical reagent.

6. The thermally-controlled sample delivery system of claim 2 wherein the chemical reagent is labeled with a detectable moiety or a chemical modifying moiety.

7. The thermally-controlled sample delivery system of claim 2 wherein the chemical reagent comprises a first set of chemical reagents and a second set of chemical reagents, and

the first set of chemical reagents is spaced apart from the second set of chemical reagents.

8. A thermally-controlled sample delivery system comprising:

a housing defining a channel, the channel comprising an open end and a closed end;

an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both;

a thermally expandable fluid disposed within the channel; and

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally expandable fluid disposed within the channel,

wherein the volume controller is used to transport a sample in the channel and the channel is a polymeric tubing material or etched or molded into the surface of a substrate.

9. A thermally-controlled sample delivery system comprising:

a housing defining a channel, the channel comprising an open end and a closed end;

an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both;

a thermally expandable fluid disposed within the channel; and

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally expandable fluid disposed within the channel,

wherein the volume controller is used to transport a sample in the channel, and the channel is formed by enclosing a longitudinally open channel which has been etched or molded into an organic or an inorganic substrate defining said housing.

10. A thermally-controlled sample delivery system comprising:

a housing defining a channel, the channel comprising an open end and a closed end;

a thermally expandable fluid disposed within the channel;

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally expandable fluid disposed within the channel; and

a second temperature control device defining a first conduit and a second conduit, where the temperature of each of the conduits is regulated independently, wherein the volume controller is used to transport a sample in the channel and the second temperature control device moves in a direction parallel to the length of the channel.

11. A scientific instrument comprising:

a thermally-controlled sample delivery system comprising;

a housing defining a channel, the channel comprising an open end and a closed end,

an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both;

a thermally expandable fluid disposed within the channel, and

a volume controller, which is a temperature control device, in thermal communication with the closed end of the channel to regulate the volume of the thermally

expandable fluid disposed within the channel, wherein the volume controller is used to transport a sample in the channel; and

a device in fluid communication with the thermally-controlled sample delivery system, wherein the device is selected from the group consisting of a blood testing device, an immunoassay device, a calorimetric device, an assay device, a toxin detection device, a chemical synthesis device, a sequencing device, a peptide or nucleotide sequencing device, a peptide or nucleotide amplification device, a peptide or nucleotide modification device, an enzyme screening device, a receptor-ligand reaction screening device, and combinations thereof.

12. The scientific instrument of claim 11 further comprising a computer in communication with the temperature control device to control the temperature control device.

13. A method for delivering a sample into a channel comprising the steps of:

(a) providing a thermally-controlled delivery system comprising;

(i) a housing defining a channel, the channel comprising an open end and a closed end;

(ii) an insulator partition within the channel, an exterior insulator in thermal communication with the channel, or a combination of both; and

(iii) a temperature control device in thermal communication with the closed end of the channel;

(b) exposing the open end of the channel to a sample; and

(c) contracting a thermally expandable fluid disposed within the channel using the temperature control device to transport at least a portion of the sample into the channel.

14. The method of claim 13 wherein introducing the sample into the channel is effected by non-thermally regulated means.

15. The method of claim 13 further comprising the step of expanding the thermally expandable fluid.

16. The method of claim 13 further comprising the step of expanding the thermally expandable fluid subsequent to step (c) to expel a portion of the sample.

17. The method of claim 13 wherein the channel comprises a capillary.

18. The method of claim 13 wherein the thermally expandable fluid comprises a gas.

19. The method of claim 13 further comprising the step of providing a second temperature control device in thermal communication with the channel for independently regulating a temperature.

20. The method of claim 13 further comprising the step of analyzing for a component in the sample.

21. A method for delivering a sample into a channel comprising the steps of:

(a) providing a thermally-controlled delivery system comprising;

(i) a housing defining a channel, the channel comprising an open end and a closed end; and

(ii) a temperature control device in thermal communication with the closed end of the channel;

(b) exposing the open end of the channel to a sample;

(c) contracting a thermally expandable fluid disposed within the channel using the temperature control device to transport at least a portion of the sample into the channel;

(d) expanding the thermally expandable fluid to expel the portion of the sample into a sample plug formation device, wherein the sample plug formation device comprises;

a housing defining

a separation channel comprising a longitudinal axis, and

an introduction channel which forms a juncture with the separation

channel;

(e) applying a first pressure differential to the introduction channel to transport a portion of the sample in communication with the introduction channel to the juncture; and

(f) applying a second pressure differential to the separation channel to transport another portion of the sample in the juncture into the separation channel to form a sample plug.

22. A method for delivering samples into a channel separated by a gas, the method comprising the steps of:

(a) providing a thermally-controlled delivery system comprising;

(i) a housing defining a channel the channel comprising an open end and a closed end; and

(ii) a temperature control device in thermal communication with the closed end of the channel;

(b) exposing the open end of the channel to a first sample;

(c) contracting a thermally expandable fluid disposed within the channel using the temperature control device to transport at least a portion of the first sample into the channel;

(d) exposing the open end of the channel to a gas;

(e) contracting a thermally expandable fluid disposed within the channel using the temperature control device to transport a volume of the gas into the channel;

(f) exposing the open end of the channel to a second sample;

(g) contracting a thermally expandable fluid disposed within the channel using the temperature control device to transport at least a portion of the second sample into the channel.

23. The method of claim 22 wherein the second sample is the first sample.