IP Library Granted Patent US 9,442,049
Granted Patent B2
US 9,442,049 · App. 13/937,891 · Granted Sep 13, 2016

Efficient processing systems and methods for biological samples

Inventors: Stephen Barker (Concord, CA); Saradha Avantsa (Concord, CA)
Assignee: Biocare Medical, LLC
G01N1/31B01F11/0071B01F13/0083G01N1/312G01N33/54346G01N33/587G01N35/0098Y10T436/25
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Quick Facts
Patent No.
US 9,442,049
App. No.
13/937,891
Granted
Sep 13, 2016
Kind
B2
Abstract

Systems and methods of sample and staining processing including compression and dynamic movement of liquids in a fluidically moving substantially contained liquid bridge perhaps between a hydrophobic wand and a hydrophilic sample support element. Embodiments may include low volume reagent and perhaps even low volume buffer wash in sample processing. In addition, antibodies can be conjugated with nanoparticles and can be used in sample processing. Exposing a sample with or without movement to AC, DC, or even a permanent magnet field may improve staining. Staining with nanoparticle reagents could be quantified using a microscope with a magnetometer below the slide viewing area. The detection of nanoparticles attached to the chemistry may facilitate the quantification of cancerous cells stained in the tissue.

Claims (29)

1. A method for efficient sample processing of a non-liquid biological sample with a dynamically moving aqueous-based processing liquid, comprising the steps of:

providing a stationary sample support with a hydrophilic surface;

providing the non-liquid biological sample fixed on the stationary sample support;

providing a moveable wand positioned above the sample support, the moveable wand having a substantially flat hydrophobic surface;

applying the aqueous-based processing liquid to the stationary sample support with the non-liquid biological sample;

contacting said substantially flat hydrophobic surface of the moveable wand with the aqueous-based processing liquid;

forming a substantially contained liquid bridge with the aqueous-based processing liquid between the substantially flat hydrophobic surface of the wand and the hydrophilic surface of the stationary sample support;

steadily oscillating the moveable wand back and forth above the stationary sample support and the non-liquid biological sample, therefore steadily oscillating the substantially contained liquid bridge over the stationary sample support and the non-liquid biological sample;

wherein contact between said liquid bridge and said hydrophilic surface of said stationary sample support comprises an acute angle;

wherein contact between said liquid bridge and said hydrophilic surface of said movable wand comprises an obtuse angle;

applying an electrical field or magnetic field to said aqueous-based processing liquid; and

efficiently processing the non-liquid biological sample with the aqueous-based processing liquid.

2. A method for efficient sample processing according to claim 1 wherein said step of applying an electrical field or magnetic field to said aqueous-based processing liquid comprises the step of changing a contact angle of said substantially contained liquid bridge with said substantially flat hydrophobic surface of the wand and said hydrophilic surface of the stationary sample support.

3. A method for efficient sample processing according to claim 1 and further comprising a step of as a result of said efficiently processing the non-liquid biological sample with the aqueous-based processing liquid, providing a stained sample.

4. A method for efficient sample processing according to claim 3 wherein said stained sample comprises a property selected from a group consisting of a sharp stain, crisp stain, a stained sample with substantially no background, a stained sample with substantially no non-specific staining, and a stained sample with substantially no hue on the sample support element.

5. A method for efficient sample processing according to claim 1 wherein said step of applying an electrical field or magnetic field to said aqueous-based processing liquid comprises the step of increasing electrostatic charge of said aqueous-based processing liquid.

6. A method for efficient sample processing according to claim 1 and further comprising the step of supporting said stationary sample support with a conducting plate.

7. A method for efficient sample processing according to claim 1 and further comprising the step of applying a voltage between said hydrophobic wand and said stationary sample support.

8. A method for efficient sample processing according to claim 7 wherein said step of applying a voltage between said hydrophobic wand and said stationary sample support comprises the step of applying a voltage selected from a group consisting of static voltage, variable negative voltage, DC bias voltage, DC voltage, and AC voltage.

9. A method for efficient sample processing according to claim 1 and further comprising the step of varying a field strength of said electrical field or said magnetic field.

10. A method for efficient sample processing according to claim 1 wherein said hydrophobic surface comprises a nano structured hydrophobic surface.

11. A method for efficient sample processing according to claim 1 and further comprising the step of pretreating said sample.

12. A method for efficient sample processing according to claim 11 wherein said step of pretreating said sample comprises the step of pretreating said sample with a process selected from a group consisting of deparaffinization, antigen retrieval, epitope retrieval, heat induced antigen retrieval, antigen retrieval, epitope retrieval, proteolytic-induced epitope retrieval, and any combination thereof.

13. A method for efficient sample processing according to claim 1 wherein said substantially contained liquid bridge comprises at least one component in said substantially contained liquid bridge.

14. A method for efficient sample processing according to claim 13 wherein said at least one component is selected from a group consisting of an antibody, a DNA probe, a RNA probe, a particle, a nanoparticle, a micro particle, a salt, a primary antibody, a secondary antibody, a tertiary antibody, a chromogenic substrate, a counterstain compatible with an antibody-enzyme conjugate, a surfactant, a component capable of reducing surface tension of a water based reagent, any combination thereof.

15. A method for efficient sample processing according to claim 1 wherein said step of efficiently processing the non-liquid biological sample with the aqueous-based processing liquid comprises the step of detecting a stain result on said non-liquid biological sample.

16. A method for efficient sample processing according to claim 15 wherein said step of detecting said stain result on said sample comprises the step of detecting said stain result with a process selected from a group of automatic detection, change in property detection, fluorescent detection, magnetic detection, electrical detection, visual detection, radioactive detection, calorimetric detection, and qualitative detection.

17. A method for efficient sample processing according to claim 1 wherein said step of steadily oscillating the moveable wand back and forth above the stationary sample support and the non-liquid biological sample comprises the step of automatically steadily oscillating the moveable wand back and forth above the stationary sample support and the non-liquid biological sample.

18. A method for efficient sample processing according to claim 1 wherein said step of steadily oscillating the moveable wand back and forth above the stationary sample support and the non-liquid biological sample comprises the step of manually steadily oscillating the moveable wand back and forth above the stationary sample support and the non-liquid biological sample.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Jun 25, 2026
From: VARAGON CAPITAL PARTNERS AGENT, LLC, AS ADMINISTRATIVE AGENT
To: BIOCARE MEDICAL LLC
Reel/Frame 075082/0723 →
SECURITY INTEREST Recorded Dec 9, 2021
From: BIOCARE MEDICAL LLC
To: VARAGON CAPITAL PARTNERS AGENT, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 058344/0799 →
RELEASE OF SECURITY INTEREST Recorded Dec 9, 2021
From: VARAGON CAPITAL PARTNERS AGENT, LLC, AS ADMINISTRATIVE AGENT
To: BIOCARE MEDICAL LLC
Reel/Frame 058351/0058 →
SECURITY INTEREST Recorded Aug 25, 2017
From: BIOCARE MEDICAL LLC
To: VARAGON CAPITAL PARTNERS AGENT, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 043401/0661 →
NUNC PRO TUNC ASSIGNMENT Recorded Jul 11, 2013
From: BARKER, STEPHEN; AVANTSA, SARADHA
To: BIOCARE MEDICAL, LLC
Reel/Frame 030779/0074 →
Continuity (4)
Continuation 13463500 · May 3, 2012
Continuation PCTUS2011055161 · Oct 6, 2011
Provisional Application 61390437 · Oct 6, 2010
Related Publication 20130309688A1 · Nov 21, 2013