Robotic end effector for frozen aliquotter and methods of taking a frozen aliquot from biological samples

• US 9,134,202 B2
• Filed: 01/26/2012
• Issued: 09/15/2015
• Est. Priority Date: 01/26/2012
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: CryoXtract Instruments, LLC
• Inventors: Bruehwiler, Michel, Sokhanvar, Saeed, Constantineau, Cole, Rosen, Melissa, Basque, Todd
• Primary Examiner(s): WEST, PAUL M
• Application Number:
  US13/359,301
• Publication Number:
  US 20130192391A1
• Time in Patent Office: 1,328 Days
• US Class Current: 1/1
• CPC Class Codes: B25J 15/0019 End effectors other than grippers
• CPC Class Codes: G01F 17/00 Methods or apparatus for determining the capacity of containers or cavities, or the volume of solid bodies measuring linear dimensions to determine volume G01B
• CPC Class Codes: G01N 1/08 involving an extracting tool, e.g. core bit
• CPC Class Codes: G01N 1/42 Low-temperature sample treatment, e.g. cryofixation
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• 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: Y10S 901/41 Tool

Abstract

A robotic end effector for collecting frozen aliquots from an array of frozen samples in a plurality of containers has a coring bit for taking frozen sample cores from the frozen samples and a frozen sample core extraction system adapted to extract frozen sample cores from the frozen samples. A fill level detection system is adapted to detect the positions of the surfaces of the frozen samples. A processor is adapted to receive signals from the fill level detection system and use the signals and information concerning operation of the frozen sample core extraction system to determine at least one of the following: (a) the amount of material contained in a frozen sample core obtained by the coring bit; and (b) the number of frozen sample cores needed from a particular frozen sample to obtain a predetermined amount of material from that frozen sample.

Claims

1. A robotic end effector for collecting frozen aliquots from an array of frozen samples, the frozen samples being contained in a plurality of containers, each frozen sample having a surface spaced from a bottom of the container, the robotic end effector comprising:

a coring bit for taking frozen sample cores from the frozen samples;

a frozen sample core extraction system adapted to move the coring bit relative to the frozen samples in a manner that extracts frozen sample cores from the frozen samples;

a fill level detection system adapted to detect the positions of the surfaces of the frozen samples; and

a processor adapted to receive signals from the fill level detection system and use the signals and information concerning operation of the frozen sample core extraction system to determine at least one of the following;

(a) the amount of material contained in a particular frozen sample; and

(b) the number of frozen sample cores needed from a particular frozen sample to obtain a predetermined amount of material from that frozen sample.

2. A robotic end effector as set forth in claim 1 wherein the frozen sample core extraction system comprises a motor adapted to rotate the coring bit.

3. A robotic end effector as set forth in claim 1 wherein the coring bit has a longitudinal axis and the frozen sample core extraction system comprises a motor adapted to move the coring bit axially.

4. A robotic end effector as set forth in claim 3 further comprising an ejector adapted to eject a frozen sample core taken by the coring bit from the coring bit, the ejector being moveable between an extended position in which the ejector extends beyond a distal end of the coring bit and a retracted position in which the ejector does not extend beyond the distal end of the coring bit.

5. A robotic end effector as set forth in claim 4 wherein the fill level detection system comprises a sensor adapted to detect contact between the ejector and the surfaces of the frozen samples.

6. A robotic end effector as set forth in claim 5 wherein the sensor is adapted to detect a change in an electrical property, wherein the change is associated with contact between the ejector and the frozen sample.

7. A robotic end effector as set forth in claim 5 wherein the ejector is adapted to be moved from the extended position toward the retracted position by the frozen samples when the ejector is in the extended position and the robotic end effector is moved so the ejector contacts one of the frozen samples, the sensor comprising a sensor that detects movement of the ejector toward the retracted position.

8. A robotic end effector as set forth in claim 1 wherein the fill level detection system comprises a sensor adapted to detect contact between the robotic end effector and the surface of a frozen sample.

9. A robotic end effector as set forth in claim 1 wherein the fill level detection system comprises an imaging system, wherein the processor is adapted to move the imaging system relative to the surface of a frozen sample, determine when the imaging system is focused on the surface, and determine the position of the surface of said frozen sample using information about the position of the imaging system when it is focused on the surface of the frozen sample.

10. A fill level detection system for a frozen aliquotter system that automatically collects frozen aliquots from an array of frozen samples, the frozen samples being contained in a plurality of containers, each frozen sample having a surface spaced from a bottom of the container, the fill level detection system comprising a processor and at least one of the following:

(a) an imaging system and a system adapted to move the imaging system toward and away from one of the frozen samples, wherein the processor is adapted to determine when the imaging system is focused on the surface of said frozen sample and use information about the position of the imaging system when it is focused on the surface of said frozen sample to determine the position of the surface of the frozen sample;

(b) a probe, a system for moving the probe toward and away from the surface of one of the frozen samples, and a sensor adapted to detect contact between the surface of said frozen sample and the probe, wherein the processor is adapted to use a signal from the sensor and information about operation of the system for moving the probe to determine the position of the surface of said frozen sample; and

(c) a robotic end effector comprising a gripper adapted to lift one of the containers and a sensor adapted to detect a weight of the lifted container by measuring a force exerted by the lifted container on the end effector, wherein the processor is adapted to use a signal from the sensor and information about the sample contained in the container to determine the position of the surface of said frozen sample,

wherein the processor is adapted to determine a distance between the surface of said frozen sample and the bottom of the respective container.

11. A fill level detection system as set forth in claim 10 wherein the fill level detection system comprises a probe, a system for moving the probe toward and away from the surface of one of the frozen samples, a sensor adapted to detect contact between the surface of said frozen sample and the probe, and a processor adapted to use a signal from the sensor and information about operation of the system for moving the probe to determine the position of the surface of said frozen sample.

12. A fill level detection system as set forth in claim 11 wherein the probe comprises an ejector that is adapted to eject a frozen sample core from the coring bit.

13. A fill level detection system as set forth in claim 12 wherein the sensor comprises a sensor adapted to detect movement of the probe associated with contact between the probe and the surface of said frozen sample.

14. A fill level detection system as set forth in claim 12 wherein the sensor is adapted to detect a change in an electrical property, wherein the change is associated with contact between the probe and the surface of said frozen sample.

15. A fill level detection system as set forth in claim 10 wherein the fill level detection system comprises a robotic end effector comprising a gripper adapted to lift one of the containers and a sensor adapted to detect a weight of the lifted container by measuring a force exerted by the lifted container on the end effector, wherein the processor is adapted to use a signal from the sensor and information about the sample contained in the container to determine the position of the surface of said frozen sample.

16. A fill level detection system as set forth in claim 15 wherein the sensor is mounted on the end effector.

17. A fill level detection system as set forth in claim 16 further comprising a locking mechanism and first and second brackets, the second bracket being connected to the first bracket so the second bracket supports the weight of the first bracket, the locking system being operable to lock the first and second brackets into position relative to one another when the locking system is in a locked state, wherein the sensor is a strain gauge connecting the first bracket to the second bracket, the strain gauge being positioned so the stain gauge supports the weight of the first bracket when the locking system is in an unlocked state.

18. A fill level detection system as set forth in claim 17, wherein the strain gauge comprises a load cell.

19. An automated method of taking a frozen aliquot from a frozen sample contained in a container, the method comprising:

using a sensor to determine the position of a surface of the frozen sample that is spaced from a bottom of the container and output a signal indicative of the position of the surface to a processor;

robotically inserting the tip of a coring bit into the frozen sample under the guidance of the processor to the bottom of the container;

robotically withdrawing the coring bit from the frozen sample to obtain a frozen sample core, the frozen sample core forming at least part of the frozen aliquot; and

ensuring that the frozen aliquot includes at least a predetermined minimum volume of sample material by using information about the position of the surface of the sample relative to the bottom of the container to determine whether or not the frozen aliquot contains at least the predetermined minimum volume of sample material.

20. An automated method as set forth in claim 19 further comprising repeating the inserting and withdrawing steps to obtain another frozen sample core from the frozen sample and adding said another frozen sample core to the frozen aliquot until the frozen aliquot contains at least the predetermined volume of sample material.

21. An automated method as set forth in claim 19 wherein finding the position of the surface of the frozen sample comprises robotically contacting the surface of the frozen sample with a probe and using a sensor to detect contact between the probe and the surface of the frozen sample.

22. An automated method as set forth in claim 21 further comprising using the probe to eject the frozen sample core from the coring bit.

23. An automated method as set forth in claim 19 wherein finding the position of the surface of the frozen sample comprises moving an imaging system relative to the sample and using the processor to determine when the imaging system is focused on the surface of the frozen sample.

24. An automated method as set forth in claim 19 further comprising placing the remaining frozen sample into a cryopreservation unit after taking the aliquot to store the remaining frozen sample for later use.