Devices and methods for tissue and cell staining

Patent metadata

Field	Value
Publication number	US-11326989-B2
Application number	US-201816758938-A
Country	US
Kind code	B2
Filing date	Oct 26, 2018
Priority date	Oct 26, 2017
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

Devices and systems are provided herein relating to a novel and rapid assay for tissue staining. Methods for using the devices and systems for analyzing tissue samples are also disclosed.

First claim

What is claimed is:

1. A device for analyzing a tissue sample, comprising:
a first plate; a second plate; a plurality of spacers; and a staining liquid, wherein:
the first and second plates are movable relative to each other into different configurations, including an open configuration and a closed configuration;
(ii) one or both plates are flexible;
(iii) each of the plates has, on its respective inner surface, a sample contact area for contacting the staining liquid and/or a tissue sample containing or suspected of containing a target analyte;
(iv) one or both of the plates comprise the plurality of spacers on a respective plate;
(v) the plurality of spacers have a predetermined substantially uniform height and a predetermined inter-spacer distance;
(vi) at least one of the plurality of spacers is inside the sample contact area; and
(vii) the staining liquid is deposited on (a) one or both of the plates in the open configuration or (b) the tissue sample;
wherein the open configuration is the configuration, in which: the two plates are partially or entirely separated apart, the spacing between the plates is not regulated by the plurality of spacers, and the tissue sample is deposited on one or both of the plates; and
wherein the closed configuration is the configuration that is configured after the open configuration; and in the closed configuration: at least part of the tissue sample and a layer of at least part of the staining liquid are between the two plates, wherein the thickness of the layer of at least part of the staining liquid is regulated by the plates, the tissue sample, and the plurality of spacers, and has an average distance between the sample surface and the surface of the plates that is equal to or less than 250 μm.

2. The device of claim 1 , further comprising a stain agent coated on one or both of the sample contact areas of the plates, wherein the staining liquid comprises a transfer solution, and wherein the stain agent is configured, upon contacting the transfer solution, to be dissolved in the transfer solution to form a liquid that stains the tissue sample.

3. A method for analyzing a tissue sample, comprising the steps of:
(a) obtaining a tissue sample containing or suspected of containing a target analyte;
(b) obtaining the device of claim 1 ;
(c) depositing, when the plates are in the open configuration, (i) the tissue sample on one or both of the plates and (ii) the staining liquid on the tissue sample or on one or both of the plates;
(d) after (c), bringing the two plates together and pressing the plates into the closed configuration; and
(e) analyzing, without washing the tissue sample, the target analyte in the tissue sample when the plates are in the closed configuration.

4. A method for analyzing a tissue sample, comprising:
(a) obtaining a tissue sample containing or suspected of containing a target analyte;
(b) obtaining the device of claim 2 ;
(c) depositing, when the plates are in the open configuration, (i) the tissue sample on one or both of the plates and (ii) the transfer solution on the tissue sample or on one or both of the plates;
(d) after (c), bringing the two plates together and pressing the plates into the closed configuration; and
(e) analyzing, without washing the tissue sample, the target analyte in the tissue sample when the plates are in the closed configuration.

5. The method of claim 3 , wherein the step (e) uses one or more imagers that image the tissue sample generating one or more images.

6. A system for analyzing a tissue sample, comprising:
(a) the device of claim 1 or 2 ; and
(b) a detector, wherein the detector detects signals of the target analyte in the tissue sample.

7. A smartphone system for tissue analysis assay, comprising:
(a) the device of claim 1 or 2 ; and
(b) a mobile communication device that comprises:
i. one or a plurality of cameras for detecting and/or imaging the tissue sample,
ii. electronics, signal processors, hardware and software for receiving and/or processing the detected signal and/or the image of the tissue sample and for remote communication; and

(c) an adaptor that is configured to accommodate the device that is in the closed configuration and be engageable to the mobile communication device, wherein when engaged with the mobile communication device, the adaptor is configured to facilitate the detection and/or imaging of the target analyte in the tissue sample at the closed configuration.

8. The method of claim 3 , wherein one or both of the plates is configured such that the tissue sample can be dried thereon at the open configuration, and wherein the tissue sample comprises bodily fluid selected from the group consisting of amniotic fluid, aqueous humour, vitreous humour, blood, breast milk, cerebrospinal fluid (CSF), cerumen (earwax), chyle, chime, endolymph, perilymph, feces, breath, gastric acid, gastric juice, lymph, mucus, pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, exhaled breath condensates, sebum, semen, sputum, sweat, synovial fluid, tears, vomit, urine, and any combination thereof.

9. The method of claim 3 , wherein the tissue sample blood is whole blood, fractionated blood, plasma or serum.

10. The method of claim 3 , wherein the tissue sample is mucus comprising nasal drainage or phlegm.

11. The device of claim 1 , wherein the staining liquid has a viscosity in the range of 0.1 to 3.5 mPa S.

12. The method of claim 3 , wherein the tissue sample is dried on one or both plates at the open configuration, and wherein the tissue sample comprises blood smear.

13. The device of claim 1 , wherein the tissue sample contact area of one or both of the plates is configured to be adhesive to the tissue sample, and wherein the tissue sample is a tissue section having a thickness in the range of 1-200 μm.

14. The device of claim 1 , wherein the tissue sample is paraffin-embedded.

15. The device of claim 1 , wherein the tissue sample is fixed.

16. The device of claim 1 , wherein the staining liquid comprises a fixative capable of fixing the tissue sample.

17. The device of claim 1 , wherein the staining liquid comprises a blocking agent.

18. The device of claim 1 , wherein the staining liquid comprises a deparaffinizing agent capable of removing paraffin in the sample.

19. The device of claim 1 , wherein the staining liquid comprises a permeabilizing agent capable of permeabilizing cells in the tissue sample that contain the target analyte.

20. The device of claim 1 , wherein the staining liquid comprises an antigen retrieval agent capable of facilitating retrieval of antigen.

21. The device of claim 1 , wherein the staining liquid comprises a detection agent that specifically labels the target analyte in the tissue sample.

22. The device of claim 1 , wherein the sample contact area of one or both plates comprises a storage site that contains a blocking agent.

23. The device of claim 1 , wherein the sample contact area of one or both plates comprises a storage site that contains a deparaffinizing agent capable of removing paraffin in the tissue sample.

24. The device of claim 1 , wherein the sample contact area of one or both plates comprises a storage site that contains a permeabilizing agent capable of permeabilizing cells in the tissue sample that contain the target analyte.

25. The device of claim 1 , wherein the sample contact area of one or both plates co

Assignees

• Essenlix Corp

Inventors

• Chou Stephen
• Ding Wei
• Li Ji

Classifications

• H04M1/72409

  by interfacing with external accessories (hands-free H04M1/60) · CPC title

• G01N21/69

  specially adapted for fluids {, e.g. molten metal} · CPC title

• G01N21/645

  Specially adapted constructive features of fluorimeters · CPC title

• G01N2021/6482

  Sample cells, cuvettes · CPC title

• G01N1/312 Primary

  for samples mounted on planar substrates · CPC title