SUBSTRATE FOR SAMPLE HANDLING

• US 20150253224A1
• Filed: 03/04/2014
• Published: 09/10/2015
• Est. Priority Date: 03/04/2013
• Status: Abandoned Application

• Current Assignee: Cell Prep Technologies, LLC
• Original Assignee: Stanley M. Liffmann
• Inventors: LIFFMANN, STANLEY M., Domenicali, Peter
• Application Number:
  US14/196,234
• Publication Number:
  US 20150253224A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: G01N 1/2813 Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 1/30 Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/1425 using an analyser being characterised by its control arrangement
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2035/1032 Dilution or aliquotting
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735
• CPC Class Codes: G01N 33/56972 White blood cells
• CPC Class Codes: G01N 35/00009 provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/00584 Control arrangements for automatic analysers
• 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: G02B 21/0096 with photometer devices photometers per se G01J
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides

Abstract

An automated microscopy system having a sample applicator configured to dispense a sample, a flexible ribbon having a surface configured to receive the sample, a light receiver, such as, for example, an automated microscope, and a ribbon controller configured to receive the flexible ribbon and guide the ribbon from the sample applicator to the light receiver. A monolayer of cells can be formed on a hydrophilic portion of the flexible ribbon and can be transported using the ribbon controller to the light receiver for analysis. The cell monolayer can be continuous.

Claims

1. A microscopy system, comprising:

a sample applicator having a tip end configured to dispense a sample;

a flexible ribbon having a hydrophilic surface configured to receive a sample from the tip;

a light receiver; and

a ribbon controller configured to receive the flexible ribbon and guide the ribbon under the light receiver.

2. The system of claim 1, wherein the flexible ribbon is formed from a material selected from the group consisting of a polymer, polyester, polystyrene, and a co-polymer.

3. The system of claim 1, wherein the flexible ribbon is optically clear in the range of about 400 nm to 700 nm.

4. The system of claim 1, wherein the ribbon controller is configured to guide the ribbon under the light receiver at a substantially constant velocity.

5. The system of claim 1, wherein the light receiver comprises at least one lens.

6. The system of claim 1, wherein the light receiver comprises a magnifying lens.

7. The system of claim 1, wherein the light receiver comprises a camera.

8. The system of claim 1, wherein the flexible ribbon has a thickness in the range of about 0.04 mm to 1.0 mm, and a width in the range of about 2.5 mm to 30 mm.

9. The system of claim 1, wherein the flexible ribbon has a length in the range of about 10 cm to 100,000 cm.

10. The system of claim 1, further comprising a roll for dispensing the ribbon, wherein the ribbon controller is configured to receive the flexible ribbon from the roll.

11. The system of claim 1, further compromising a mechanism for cutting the ribbon into a plurality or pieces, wherein the ribbon controller is configured to receive at least one piece of the plurality of pieces.

12. The system of claim 11, further comprising a collector for receiving the pieces of ribbon following passage under the light receiver.

13. The system of claim 1, wherein the sample applicator is configured to dispense a monolayer of cells on the hydrophilic surface of ribbon.

14. The system of claim 1, wherein the sample applicator comprises an applicator pump.

15. The system of claim 1, further comprising:

a diluent vessel in operable communication with the sample applicator, wherein the diluent vessel comprises at least one diluent; and

a diluent pump configured to deliver at least one diluent to the sample applicator.

16. A method for preparing a sample for microscopy, the method comprising:

engaging a flexible piece of ribbon having a hydrophilic surface with at least one ribbon controller;

dispensing cells from a tip of a sample applicator comprising the sample on to the hydrophilic surface; and

guiding the flexible ribbon under a dispenser configured to dispense fixing and/or staining solution using the at least one ribbon controller.

17. The method of claim 16, wherein the dispenser is configured to use methanol and Wright Giemsa stain.

18. The method of claim 16, wherein the flexible ribbon is optically clear in the range of about 400 nm to about 700 nm.

19. The method of claim 16, further comprising guiding the flexible ribbon with at least one ribbon controller under a light receiver, wherein the light receiver is configured to analyze cells.

20. The method of claim 19, wherein the light receiver comprises a camera that is configured to acquire images of the cells.

21. The method of claim 16, wherein the sample applicator comprises an applicator pump that dispenses cells from the tip of the sample applicator.

22. The method of claim 16, further comprising using a storage vessel having at least one diluent in operable communication with the sample applicator, and a diluent pump that delivers the at least one diluent to the sample applicator.

23. The method of claim 16, wherein the sample applicator dispenses a monolayer of cells on to the hydrophilic surface.

24. The method of claim 16, further comprising executing computer-executable instructions stored on at least one tangible, non-transitory computer-readable storage medium such that the computer-executable instructions, when executed by at least one processor, cause a computing device to instruct the sample applicator to vary the distance between the tip of the sample applicator and the flexible ribbon.

25. The method of claim 16, further comprising:

executing computer-executable instructions stored on at least one tangible, non-transitory computer-readable storage medium such that the computer-executable instructions, when executed by at least one processor, cause a computing device to perform at least one of;

instructing the sample applicator to dispense a sample on to the hydrophilic surface;

instructing a diluent vessel to dilute or not dilute the sample;

instructing the at least one ribbon controller to vary the distance between the ribbon and the tip of the sample applicator;

instructing the at least one ribbon controller to alter a tension of the ribbon;

instructing the at least one ribbon controller in what direction to guide the ribbon;

instructing the at least one ribbon controller to move the ribbon at a specified velocity, and/or change the velocity of the ribbon relative to a light receiver;

instructing the light receiver to adjust focus in response to a signal received by the light receiver;

instructing the sample applicator to dispense the sample at a specific rate; and

instructing the sample applicator to dispense the sample at a specific volume.

26. A method for analyzing cells, comprising:

engaging a portion of a flexible ribbon having a hydrophilic surface with at least one ribbon controller;

dispensing cells from a tip of a sample applicator comprising a sample of the cells on the hydrophilic surface;

guiding the portion of the flexible ribbon under a dispenser configured to dispense fixing and/or staining solution using the at least one ribbon controller; and

guiding the flexible ribbon with at least one ribbon controller under a light receiver, wherein the light receiver is configured to analyze cells.

27. The method of claim 26, wherein the flexible ribbon is guided under the light receiver at a substantially constant velocity.

28. The method of claim 26, wherein the flexible ribbon is optically clear in the range of about 400 nm to about 700 nm.

29. The method of claim 26, wherein the light receiver comprises a camera configured to acquire images of cells.

30. The method of claim 26, wherein the sample applicator comprises an applicator pump configured to dispense cells from the tip of the sample applicator.

31. The method of claim 26, further comprising using a storage vessel having at least one diluent in operable communication with the sample applicator, and a diluent pump that delivers the at least one diluent to the sample applicator.

32. The method of claim 26, wherein the sample applicator dispenses a monolayer of cells on to the hydrophilic surface.

33. The method of claim 26, further comprising executing computer-executable instructions stored on at least one tangible, non-transitory computer-readable storage medium such that the computer-executable instructions, when executed by at least one processor, cause a computing device to instruct the sample applicator to vary the distance between the tip of the sample applicator and the flexible ribbon.

34. The method of claim 26, further comprising:

executing computer-executable instructions stored on at least one tangible, non-transitory computer-readable storage medium such that, the computer-executable instructions, when executed by at least one processor, cause a computing device to perform at least one of;

instructing the sample applicator to dispense the sample on to the hydrophilic surface;

instructing a diluent vessel to dilute or not dilute the sample;

instructing the at least one ribbon controller to vary the distance between the ribbon and the tip of the sample applicator;

instructing the at least one ribbon controller to alter a tension of the ribbon;

instructing the at least one ribbon controller in what direction to guide the ribbon;

instructing the at least one ribbon controller to move the ribbon at a specified velocity, and/or change the velocity of the ribbon relative the light receiver;

instructing the at least one light receiver to adjust focus in response to a signal received by the light receiver;

instructing the sample applicator to dispense the sample at a specific rate; and

instructing the sample applicator to dispense the sample at a specific volume.

35. The method of claim 26, further comprising acquiring a plurality of images of the cells using the light receiver, and analyzing the plurality of images to obtain a 5-part differential.

36. The method of claim 26, wherein the dispenser is configured to use methanol and Wright Giemsa stain.

37. A kit, comprising:

a flexible ribbon having a hydrophilic surface configured to receive a biological sample, wherein the flexible ribbon is formed from a material selected from the group consisting of a polyester, polystyrene, and mixtures thereof, and wherein the flexible ribbon is optically clear in the range of about 400 nm to about 700 nm; and

instructions for installing the ribbon on a microscopy system comprising a sample applicator having a tip end, a light receiver, and at least one ribbon controller to receive and guide the ribbon under the light receiver.

38. A system for analyzing cells from blood, bone marrow or cell culture comprising:

an applicator comprising a tip adapted for applying a single flow of cells in a monolayer on a glass substrate.

a light or image receiving device adapted for capturing images and fluorescence from the cells on the glass substrate; and

a computer adapted for

instructing the system to aspirate a sample from a collection vessel,

instructing the system to position the tip just above the glass substrate,

instructing the system to move the glass substrate at a predetermined velocity, and

instructing the applicator to dispense the sample at a predetermined rate such that a monolayer of cells results with a width that is between 0.6 and 2.0 mm and a length that is between 6 and 12 cm for a 5 part differential white cell count.