Temperature controlled microfabricated two-pin liquid sample dispensing system

• US 7,686,967 B2
• Filed: 06/08/2007
• Issued: 03/30/2010
• Est. Priority Date: 12/21/2001
• Status: Expired due to Term

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Inventors: Gilbert, John R., Böhm, Sebastian
• Primary Examiner(s): ALANKO, ANITA KAREN
• Application Number:
  US11/811,021
• Publication Number:
  US 20070298171A1
• Time in Patent Office: 1,026 Days
• Field of Search: None
• US Class Current: 216/2
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0248 Prongs, quill pen type dispenser
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: B01L 9/543 for disposable pipette tips, e.g. racks or cassettes
• CPC Class Codes: G01N 2035/1037 Using surface tension, e.g. pins or wires
• CPC Class Codes: Y10S 977/888 Shaping or removal of materials, e.g. etching
• CPC Class Codes: Y10T 29/49 Method of mechanical manufacture
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A cooled liquid sample dispensing system comprises a pair of pins for holding a droplet of liquid therebetween and a cooling element. Each pin includes a tip spaced predetermined distance from the other pin to define a sample acquisition region. The pins acquire and hold a droplet of the liquid sample in the sample acquisition region formed in the space between the tips and apply the droplet to a selected sample handing system. The cooling element, when activated, cools the droplet of liquid to reduce evaporation.

Claims

1. A method of manufacturing a pin-based fluid handling system, comprising the steps of:

providing a substrate,

imprinting a pattern defining a plurality of components of the pin-based fluid handling system on the substrate;

etching the substrate around the pattern to remove excess material from the substrate and form the components of the fluid handling system; and

coupling a cooling element to one of the components for cooling at least one of the plurality of components of the fluid handling system.

2. The method of claim 1, wherein the components of the fluid handling system comprise at least one fluid handling pin.

3. The method of claim 1, wherein the components of the fluid handling system comprise:

a holder,

a first pin coupled to the holder, and

a second pin coupled to the holder,

wherein the second pin is spaced from the first pin to define a channel therebetween, the channel sized and dimensioned for receiving and retaining a fluid sample by capillary action.

4. The method of claim 3, wherein the first pin and second pin extend from and are integral with the holder.

5. The method of claim 1, wherein the components of the fluid handling system comprise a base, a first pin tip connected to the base and a second pin tip connected to the base and spaced from the first pin tip to form a cavity for receiving a fluid volume.

6. The method of claim 5, further comprising the step of applying a chemical coating for enhancing fluid handling to one of said first pin tip and said second pin tip.

7. The method of claim 6, wherein the chemical coating comprises one of a hydrophilic coating, a hydrophobic coating, and combinations thereof.

8. The method of claim 7, wherein the step of applying the chemical coating comprises applying a coating mask defining a coating pattern to the fluid handling system and applying the coating in a predetermined pattern, defined by the coating mask.

9. The method of claim 1, further comprising the step of coupling a temperature sensor to a component of the fluid handling system.

10. The method of claim 9, further comprising the step of connecting the temperature sensor to a controller for comparing an actual temperature measured using the temperature sensor to a reference temperature, and for selectively actuating the cooling element to adjust the actual temperature to equal the reference temperature.

11. The method of claim 10, wherein the temperature sensor comprises a thin-film resistor.

12. The method of claim 1, wherein the substrate comprises a silicon wafer.

13. The method of claim 1, wherein the substrate comprises one of glass, plastic, silicon and combinations thereof.

14. The method of claim 1, wherein the step of imprinting the pattern comprises applying a photo-mask containing the pattern to the substrate, applying a photoresist layer and projecting light through the photo-mask to create the pattern.

15. The method of claim 1, wherein the cooling element is a Peltier element.

16. The method of claim 1, further comprising the step of forming a second fluid handling system on the substrate.

17. The method of claim 16, wherein the step of forming the second fluid handling system comprises the steps of:

imprinting a second pattern defining a plurality components of the second fluid handling system on the substrate in a different region of the substrate from a region in which the first fluid handling system is formed;

etching the substrate around the second pattern to remove excess material from the substrate and form the components of the second fluid handling system; and

coupling a second cooling element to one of the components of the second fluid handling system.

18. A method of manufacturing a pin-based fluid handling system, comprising the steps of:

etching a plurality of components of a fluid handling system in a substrate, the plurality of components including a holder, a first pin tip and a second pin tip spaced from the first pin tip to define a sample acquisition region; and

placing a cooling element in temperature communication with one of the components for cooling the fluid handling system.

19. The method of claim 18, wherein the substrate comprises one of silicon, glass, plastic and combinations thereof.

20. The method of claim 18, wherein the cooling element is a Peltier element.

21. The method of claim 18, wherein the cooling element is coupled to the holder.

22. The method of claim 18, wherein the cooling element is coupled to one to the first pin tip and the second pin tip.

23. The method of claim 18, further comprising the step of applying a chemical coating for enhancing fluid handling to one of the first pin tip and the second pin tip.

24. The method of claim 18, further comprising the step of coupling a temperature sensor to a component of the fluid handling system.

25. The method of claim 24, further comprising the step of connecting the temperature sensor to a controller for comparing an actual temperature measured using the temperature sensor to a reference temperature and for selectively actuating the cooling element to adjust the actual temperature to equal the reference temperature.

26. The method of claim 21, wherein the temperature sensor comprises a thin-film resistor.

27. The method of claim 18, wherein the fluid-handling system is formed in a first region of the substrate, and a second fluid-handling system is formed in a second region of the substrate.

28. A method of manufacturing a pin-based fluid handling system, comprising the steps of:

etching a fluid handling system from a substrate, the fluid handling system comprising a plurality of components; and

coupling a temperature control system to one of the components for controlling a temperature of at least one of the plurality of components of the fluid handling system.

29. The method of claim 28, wherein the temperature control system comprises:

a temperature sensor for measuring a temperature of a component of the fluid handling system;

a cooling element for selectively cooling a component of the fluid handling system; and

a controller in communication with the temperature sensor and the cooling element for comparing an actual temperature measured using the temperature sensor to a reference temperature and for selectively actuating the cooling element to adjust the actual temperature to equal the reference temperature.

30. The method of claim 29, wherein the temperature sensor comprises a thin-film resistor.

31. The method of claim 29, wherein the cooling element comprises a Peltier element.

32. The method of claim 28, wherein the components of the fluid handling system comprise at least one fluid handling pin.

33. The method of claim 28, wherein the components of the fluid handling system comprise a holder, a first pin coupled to the holder, and a second pin coupled to the holder, wherein the second pin is spaced from the first pin to define a channel therebetween, the channel sized and dimensioned for receiving and retaining a fluid sample by capillary action.

34. The method of claim 33, further comprising the step of applying a chemical coating for enhancing fluid handling to one of the first pin tip and the second pin tip.

35. The method of claim 28, further comprising the step of imprinting a pattern defining the plurality components of the fluid handling system on the substrate prior to the step of etching the substrate.

36. The method of claim 35, wherein the step of imprinting a pattern comprises the steps of:

applying a photo-mask containing the pattern to the substrate,

applying a photoresist layer to the substrate and photo-mask, and

projecting light through the photo-mask to create the pattern.

37. A method of manufacturing an array of fluid handling systems comprising the steps of:

providing a substrate;

for each fluid handling system in the array, imprinting a pattern defining a plurality of components of the associated fluid handling system on the substrate;

for each imprinted pattern, etching the substrate around the pattern to remove excess material from the substrate and form the components of the associated fluid handling system; and

for each thus-formed fluid handling system, coupling a cooling element to a component for cooling the associated fluid handling system.

38. The method of claim 37, wherein the substrate comprises a silicon wafer.

39. The method of claim 37, wherein each fluid handling system comprises a holder, a first pin coupled to the holder, and a second pin coupled to the holder, wherein the second pin is spaced from the first pin to define a channel therebetween, the channel sized and dimensioned for receiving and retaining a fluid sample by capillary action.

40. The method of claim 37, wherein the array comprises at least about 300 fluid handling systems formed in the substrate.

41. The method of claim 37, wherein the step of imprinting the pattern comprises applying a photo-mask containing an array of patterns to the substrate, applying a photoresist layer and projecting light through the photo-mask to create the array of patterns.

42. The method of claim 37, wherein the cooling elements are Peltier elements.