System and method for preparing a biological sample for analysis

• US 10,379,014 B2
• Filed: 11/21/2016
• Issued: 08/13/2019
• Est. Priority Date: 11/23/2015
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Calatzis, Andreas, Leyser, Harald
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US15/356,694
• Publication Number:
  US 20170146437A1
• Time in Patent Office: 995 Days
• 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 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

Abstract

A method for preparing a biological sample for analysis is provided that includes moving a continuous substrate film past a sample applicator unit including one or more sample applicators and applying at least one trace of a biological sample to be analyzed onto the continuous substrate film by the sample applicator unit.

Claims

1. A method for preparing a biological sample for analysis, the method comprising:

moving a continuous substrate film past a sample applicator unit including one or more sample applicators; and

,

applying, while moving the continuous substrate film, at least one trace of a biological sample to be analyzed onto the continuous substrate film by the sample applicator unit, wherein the biological sample includes cells and wherein the at least one trace of a biological sample forms substantially a monolayer of cells on a surface of the continuous substrate film.

2. The method of claim 1 wherein the applicator unit includes one sample applicator or two or more sample applicators.

3. The method of claim 1 further comprising moving each sample applicator to vary the distance between the applicator and the continuous substrate film, and/or to vary the force employed to apply the biological sample onto the continuous substrate film, wherein the sample applicators are stationary during the applying step, except for a movement to vary the distance between said applicator and the continuous substrate film, and/or to vary the force employed to apply the biological sample onto the continuous substrate film.

4. The method of claim 3 wherein each sample applicator moves only among a straight trajectory to vary the distance of said applicator to the continuous substrate film, and/or to vary the force of the application process onto the continuous substrate film.

5. The method of claim 1, wherein the moving the continuous substrate film includes supplying the continuous substrate film from a supply roll and receiving the continuous substrate film in a container or on a waste roll after the at least one trace of a biological sample applied to the continuous substrate film has been analyzed.

6. The method of claim 1, wherein the biological sample comprises a bodily fluid or a constituent thereof.

7. The method of claim 6, wherein the bodily fluid is blood or a constituent of blood.

8. The method of claim 1, wherein the sample applicator unit is configured to apply two or more traces of the biological sample.

9. The method of claim 1 further comprising adding a staining agent to the biological sample, wherein adding the staining agent comprises spraying the staining agent onto the trace of the biological sample, printing the staining agent onto the trace of the biological sample, or moving the continuous substrate film with the trace of the biological sample through a bath including the staining agent.

10. The method of claim 1 further comprising moving the trace of the biological sample past an imaging stage, wherein said imaging stage is configured to take one or more images of the trace of the biological sample.

11. The method of claim 10, wherein the imaging stage is stationary over a surface of the continuous substrate film except for a movement in a direction perpendicular to a surface of the continuous substrate film.

12. The method of claim 1, wherein the continuous substrate film is supported by a support in an area where the trace of the biological sample to be analyzed is applied onto the continuous substrate film by the one or more applicators, and/or wherein the continuous substrate film is supported by a support in an area where the trace of the biological sample to be analyzed is imaged by an imaging stage, wherein the support includes a roller.

13. The method of claim 1, wherein the sample applicator unit has a tip and said method comprises controlling the flow rate through the tip while applying the at least one trace of the biological sample onto the surface of the continuous substrate film.

14. The method of claim 1, further comprising controlling relative speed with which the transportation device moves the continuous substrate film under the sample applicator unit.

15. The method of claim 1, wherein the sample applicator unit has a tip and said method comprises controlling height of the tip over the continuous substrate film while applying the at least one trace of the biological sample onto the surface of the continuous substrate film.

16. The method of claim 1, wherein the sample applicator unit has a tip and said method comprises controlling the flow rate through the tip while applying the at least one trace of the biological sample onto the surface of the continuous substrate film, and wherein the flow rate through the tip is between 0.005 and 1 microliter per second.

17. The method of claim 1, wherein the sample applicator unit has a tip and said method comprises controlling relative speed with which the transportation device moves the continuous substrate film under the tip, and wherein the continuous substrate film is moving at a speed of between 1 and 120 millimeters per second under the tip.

18. The method of claim 1, wherein the sample applicator unit has a tip and said method comprises controlling height of the tip over the continuous substrate film while applying the at least one trace of the biological sample onto the surface of the continuous substrate film, and wherein the height is between 2 microns and 120 microns.

19. An apparatus for preparing a biological sample for analysis, the apparatus comprising:

a film transportation device configured to move a continuous substrate film past a sample applicator unit; and

,

a sample applicator unit including one or more sample applicators configured to apply a trace of a biological sample to be analyzed onto the continuous substrate film when moved by the film transportation device, wherein the biological sample includes cells and wherein the trace of a biological sample forms substantially a monolayer of cells on a surface of the continuous substrate film.

20. The apparatus of claim 19, wherein the continuous substrate film includes a coating applied to a surface of the continuous substrate film onto which the trace of a biological sample for analysis is to be deposited to improve adherence of the trace of the biological sample.