INTEGRATED ROBOTIC SAMPLE TRANSFER DEVICE

• US 20090180931A1
• Filed: 09/16/2008
• Published: 07/16/2009
• Est. Priority Date: 09/17/2007
• Status: Abandoned Application

• Current Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: Cuzens, Justin, Capella, Richard, Silbert, Rolf
• Application Number:
  US12/211,796
• Publication Number:
  US 20090180931A1
• Time in Patent Office: Days
• US Class Current: 422/63
• 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 2219/00277 Apparatus
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01L 2400/025 tapping tip on substrate
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0251 Pin and ring type or pin in tube type dispenser
• CPC Class Codes: G01N 2035/1037 Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: Y10S 901/24 Stepper motor

Abstract

Embodiments include integrated robotic sample transfer devices and components thereof which are used for reliably and accurately transferring small samples of material from one registered position to another registered position. Such transfers of material may be carried out by a single pin tool or an array of pin tools of a pin tool head assembly of robotic sample transfer devices. Some embodiments also include automated cleaning of the pin tools used to transfer the sample material. Some embodiments are fully integrated units having internal fluid supply and waste tanks, vacuum source, fluid pumps, controllers and user interface devices.

Claims

1. A robotic sample transfer device, comprising:

a substantially horizontal work surface including a plurality of functional elements configured for small sample processing;

a three axis robotic positioning assembly having a fixed mount portion secured in fixed relation with the work surface, a translatable carrier configured to be translatable in three axes with respect to the fixed mount portion and working surface and having a stepper motor corresponding to each axis and at least one linear encoder assembly configured to generate position data for at least one axis;

at least one pin tool coupled to the translatable carrier; and

a controller in communication with the stepper motors of each of the three axes of the three axis robotic positioning assembly and the at least one linear encoder assembly.

2. The sample transfer device of claim 1 further comprising a housing disposed about the work surface, three axis robotic positioning assembly and controller.

3. The sample transfer device of claim 2 further comprising a graphic user interface on an exterior of the housing and operatively coupled to the controller for providing user input to the controller.

4. The sample transfer device of claim 1 wherein the three axes of the three axis robotic positioning assembly are substantially orthogonal to each other.

5. The sample transfer device of claim 1 wherein the three axis robotic positioning assembly further comprises a bar code reader.

6. The sample transfer device of claim 1 wherein the three axis robotic positioning assembly further comprises an imaging camera translatable in at least two axes and operatively coupled to an image processor.

7. The sample transfer device of claim 1 wherein the controller comprises at least one processor which is disposed within the housing at a level which is above the level of the work surface.

8. A robotic sample transfer device, comprising:

a housing;

a substantially horizontal work surface disposed within the housing;

a three axis robotic positioning assembly disposed within the housing having a fixed mount portion secured in fixed relation with the work surface and a translatable carrier member translatable in three different axes with respect to the fixed mount portion and work surface;

at least one pin tool coupled to the translatable carrier having a shaft and a sample reservoir in a distal end of the shaft;

a plurality of functional elements disposed on the work surface having a nominal upper surface at substantially the same height; and

a controller operatively coupled to the three axis robotic positioning assembly.

9. The sample transfer system of claim 8 further comprising an imaging camera movable in at least the x-y plane substantially parallel to the work surface and having a shallow range of focus and focused at the nominal upper surface of the functional elements.

10. The sample transfer device of claim 8 wherein the functional elements comprise a vacuum drying station, a fluid rinse station, a microtiter plate having an array or regularly space sample supply wells and a chip having an array of regularly spaced sample deposition sites.

11. The sample transfer device of claim 8 further comprising a pin tool head assembly having an array of regularly spaced pin tools secured to the translatable carrier and wherein the vacuum drying station includes a plurality of regularly spaced vacuum drying ports corresponding to the spacing of the pin tools of the pin tool head assembly, the fluid rinse station includes individual rinse tubes corresponding to each of the pin tools of the array of regularly spaced pin tools of the pin tool head assembly.

12. The sample transfer device of claim 10 further comprising a self-leveling gravity fed ultrasonic cleaning well and an ultrasonic cleaning fluid reservoir having a supply port configured to couple into fluid communication with the ultrasonic cleaning well when coupled to an inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well.

13. The sample transfer device of claim 10 wherein the ultrasonic cleaning fluid reservoir further comprises a ball valve which is configured to seal the supply port when the fluid reservoir is removed from the inlet port of the ultrasonic cleaning well.

14. The sample transfer device of claim 8 wherein the controller comprises at least one processor which is disposed within the housing at a level which is above the level of the work surface.

15. An integrated robotic sample transfer device, comprising:

a housing;

a three axis robotic positioning assembly disposed within the housing having a fixed mount portion, a translatable carrier translatable in three axes with respect to the fixed mount portion and working surface and having a stepper motor corresponding to each axis and at least one linear encoder assembly for generating position data for at least one axis of the translatable carrier;

a pin tool head assembly secured to the translatable carrier member having an array of regularly spaced pin tools with sample reservoirs disposed in the distal ends thereof and configured for axial displacement relative to a pin head body secured to the translatable carrier of the three axis robotic positioning assembly;

a substantially horizontal work surface disposed within the housing and secured in fixed relation to the fixed mount portion of the three axis positioning assembly and having a fluid rinse station, a vacuum drying station including a plurality of regularly spaced vacuum drying ports corresponding to the regular spacing of the array of pin tools, a self-leveling ultrasonic cleaning well and a microtiter plate mount block configured to releasably secure a sample well;

a controller including a processor disposed within the housing at a position which is above the level of the work surface;

a rinse fluid supply tank in fluid communication with the fluid rinse station and disposed within the housing;

a waste fluid tank in fluid communication with an overflow basin of the fluid rinse station and disposed within the housing;

a vacuum source in fluid communication with the vacuum drying station; and

an ultrasonic cleaning fluid reservoir in fluid communication with a self-leveling ultrasonic cleaning well.

16. The sample transfer device of claim 15 wherein in the ultrasonic cleaning fluid reservoir comprises a gravity feed reservoir having a supply port configured to couple into fluid communication with the ultrasonic cleaning well when coupled to an inlet port of the ultrasonic cleaning well and be substantially sealed when the removed from the inlet port of the ultrasonic cleaning well.

17. The sample transfer device of claim 15 further comprising a rinse fluid supply tank fluid level indicator.

18. The sample transfer device of claim 15 further comprising a rinse fluid supply pump disposed within the housing, in fluid communication with the rinse fluid supply tank and fluid rinse station and configured to pump rinse fluid from the rinse fluid supply tank to the fluid rinse station.

19. The sample transfer device of claim 15 further comprising a waste fluid tank fluid level indicator.

20. The sample transfer device of claim 15 further comprising a vacuum drying supply tank in fluid communication with the vacuum drying ports of the vacuum drying station.

21. The sample transfer device of claim 20 further comprising a vacuum pump in fluid communication with the vacuum drying supply tank.

22. The sample transfer device of claim 15 wherein a nominal upper surface of the fluid rinse station, nominal upper surface of the vacuum drying station, nominal upper surface of the ultrasonic cleaning well, nominal upper surface of a chip disposed in the chip mount block and microtiter plate/sample well mounted in the sample well mount blocks all being at substantially the same z-axis level.

23. The sample transfer device of claim 15 further comprising an imaging camera and image processing controller.

24. The sample transfer device of claim 15 further comprising a bar code reader head and bar code reader processor in communication with the bar code reading head and controller.

25. The sample transfer device of claim 15 wherein the fluid rinse station comprises an array of regularly spaced individual rinse tubes having a regular spacing corresponding to the regular spacing of the pin tools of the pin tool head assembly.

26. The sample transfer device of claim 15 further comprising a door on the housing covering an opening to a processing chamber disposed within the housing.

27. The sample transfer device of claim 15 wherein the controller comprises an assembly of electronics and logic circuits which are disposed within the housing at a position which is above the level of the work surface.

28. The sample transfer device of claim 15 further comprising a universal power supply in communication with the controller that produces a constant output voltage with varied input voltage to allow device to operate in varying countries.

29. The sample transfer device of claim 15 wherein the entire dry weight of the device is less than about 150 pounds.

30. The sample transfer device of claim 15 further comprising a graphic user interface disposed on an outer surface of the housing and in communication with the controller.

31. The sample transfer device of claim 15 further comprising a humidity sensor disposed within the processing chamber of the device and in communication with the controller which is configured to sense the humidity within the processing chamber.

32. The sample transfer device of claim 31 further comprising closed loop feedback from the humidity sensor with the controller in conjunction with a humidity control device for maintaining a substantially constant humidity within the processing chamber.

33. The sample transfer device of claim 15 further comprising a temperature sensor disposed within the processing chamber of the sample transfer device in communication with the controller which is configured to sense the temperature within the processing chamber.

34. The sample transfer device of claim 33 further comprising closed loop feedback from the temperature sensor with the controller and a temperature control device for maintaining a substantially constant temperature within the processing chamber.

35. A method of registering the position of a pin tool head assembly of a robotic sample transfer device relative to sample deposition sites on a chip, comprising:

providing a robotic sample transfer device having a work surface with a plurality of functional elements with a nominal upper surface at substantially the same level and a three axis positioning system with a camera and pin tool head assembly secured to a translatable carrier thereof;

imaging the nominal upper surfaces of functional elements disposed on work surface with the camera;

processing the image data of the nominal upper surfaces of the functional elements from the camera to determine the approximate position of the pin tool head assembly relative to the functional elements;

using the approximate position data to move the camera to a first chip having an array of regularly spaced sample deposition sites and an array of regularly spaced fiducial marks disposed between the sample deposition sites;

imaging fiducial marks on the first chip;

processing the image data of fiducial marks on the first chip;

obtaining feedback regarding a position of the pin tool head assembly from linear encoders of three axes of a three axis robotic positioning system;

comparing encoder feedback with image processing feedback and look up table data to determine the precise position of the pin tools of the pin tool head assembly with respect to the sample deposition sites on the first chip.

36. The method of claim 35 further comprising repeating the process for multiple chips.

37. The method of claim 35 wherein the precise position of the pin tools of the pin tool head assembly with respect to the sample deposition sites on the first chip is determined to within about 1 micron to about 10 microns.

38. A method of dispensing calibration material onto a chip, comprising:

providing a chip having a first array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof and at least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip and which is off pitch with respect to the regular spacing of the first array of regularly spaced sample deposition sites of the chip;

providing a robotic sample transfer device having a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar in a relaxed state and which have a regular spacing which is the same as the regular spacing of the first array of sample deposition sites or an integer multiple thereof and configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof;

loading sample reservoirs of the array of regularly spaced pin tools of the robotic sample transfer device with calibration material;

dispensing calibration material from the pin tools of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array.

39. The method of claim 38 wherein the chip comprises a second array of regularly spaced sample deposition sites for receiving calibration material sample which are off pitch with respect to the first array of regularly spaced sample deposition sites and further comprising dispensing calibration material from pin tools of the robotic sample transfer device to the second array of sample deposition sites for receiving calibration material such that the pin tools which are not aligned with sample deposition sites for receiving calibration material of the second array are off pitch with respect to the first array of regularly spaced sample deposition sites of the chip and do not contact any of the regularly spaced sample deposition sites of the first array.

40. The method of claim 38 wherein the first array of regularly spaced sample deposition sites comprises an array of regularly spaced mass spectrometry sample deposition sites.

41. A pin tool displacement block for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device in an axial direction, comprising:

a block body having a bottom surface and a plurality of parallel slots formed into the block body portion substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing of pin tools of a pin tool head assembly and having a transverse dimension sized to allow easy movement of a width of a nominal shaft of the pin tools in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools; and

at least one relieved portion in a slot which has a transverse dimension sized to allow easy downward movement of the enlarged portion of a pin tool shaft which is greater than the transverse dimension of the slot and which extends from a top surface of the block body towards the bottom surface.

42. The pin tool displacement block of claim 41 wherein the at least one relieved portion terminates at a stop surface which is spaced from the bottom surface.

43. The pin tool displacement block of claim 41 wherein the at least one relieved portion extends completely from the top surface to the bottom surface and is configured to allow the enlarged portion of a pin tool shaft to pass completely through the block body.

44. The pin tool displacement block of claim 41 wherein the relieved portion is configured to mechanically capture the enlarged portion of a pin tool disposed therein in a lateral direction.

45. The pin tool displacement block of claim 41 wherein the enlarged portion of a shaft of a pin tool comprises a collar member and the stop surface of the at least one relieved portion is configured to prevent axial movement of the collar member and mechanically capture a collar disposed therein member to prevent lateral displacement of the block body when the block is deployed in a pin tool head assembly.

46. The pin tool displacement block of claim 41 wherein the top surface and bottom surface of the block body are substantially flat and substantially parallel to each other.

47. The pin tool displacement block of claim 41 wherein the block body comprises an inert material.

48. The pin tool displacement block of claim 46 wherein the inert material comprises Delrin.

49. The pin tool displacement block of claim 41 further comprising a handle member secured to the block body.

50. The pin tool displacement block of claim 41 having a reversible configuration wherein when the block is oriented in a first direction a first pin or set of pins is active and when oriented a second way a second pin or set of pins is active which is different from the first set.

51. The pin tool displacement block of claim 50 wherein the first direction is about 180 degrees from the second direction.

52. A method for selectively displacing at least one pin tool of a pin tool head assembly of a robotic sample transfer device, comprising:

providing a pin tool displacement block including a block body having a bottom surface and a plurality of parallel slots formed into the block body portion substantially perpendicular to the bottom surface with a predetermined regular spacing configured to correspond to regular spacing of pin tools of a pin tool head assembly and having a transverse dimension sized to allow easy movement of a width of a nominal shaft of the pin tools in the slots but restrictive of movement of an enlarged portion of the shaft of the pin tools, and at least one relieved portion in a slot which has a transverse dimension sized to allow easy downward movement of the enlarged portion of a pin tool shaft which is greater than the transverse dimension of the slot and which extends from a top surface of the block body towards the bottom surface;

displacing an array of pin tools of a pin tool head assembly by depressing the pin tools against a flat surface;

deploying the pin tool displacement block into the pin tool head assembly such that the parallel slots of the pin tool displacement block slide over rows of the array of pin tools of the pin tool head assembly; and

allowing the pin tools to return to a relaxed state by retracting the pin tool head assembly from the flat surface with at least one of the pin tools axially displaced in the relaxed state.

53. A method of dispensing calibration material onto a chip, comprising:

providing a chip having an array of regularly spaced sample deposition sites disposed on a substantially flat working surface thereof and at least one sample deposition site for receiving calibration material which is also disposed on the flat working surface of the chip;

providing a robotic sample transfer device having a pin tool head assembly with an array of regularly spaced pin tools having distal ends which are substantially coplanar in a relaxed state and which have a regular spacing which is the same as the regular spacing of the first array of sample deposition sites or an integer multiple thereof and configured to align with the array of regularly spaced sample deposition sites of the chip or a subset thereof;

axially displacing at least one of the pin tools of the pin tool head assembly with a pin tool displacement block;

loading a sample reservoir of at least one un-displaced pin tool of the robotic sample transfer device with calibration material;

dispensing calibration material from the at least one un-displaced pin tool of the robotic sample transfer device to the at least one sample deposition site for receiving calibration material such that the pin tools which are displaced by the pin tool displacement block do not contact the chip.

54. The method of claim 53 wherein the array of regularly spaced sample deposition sites comprises an array of regularly spaced mass spectrometry sample deposition sites.