Sample manipulation and assay with rapid temperature change

Patent metadata

Field	Value
Publication number	US-2021069709-A1
Application number	US-201816772396-A
Country	US
Kind code	A1
Filing date	Dec 12, 2018
Priority date	Dec 12, 2017
Publication date	Mar 11, 2021
Grant date	—

Abstract

Among other things, the present invention is related to devices and methods of performing biological and chemical assays, particularly an easy sample manipulation and/or a rapid change or a rapid thermal cycling of a sample temperature is needed (e.g. Polymerase Chain Reaction (PCR) for amplifying nucleic acids).

First claim

1 . A device for fluidically isolating a portion of a sample, comprising: a first plate, a second plate, a plurality of spacers, and a clamp, wherein:
i. the first plate and the second plate are movable relative to each other into different configurations, including an open configuration and a closed configuration, wherein one or both of the plates is flexible, wherein each of the plates comprises, on its respective surface, a sample contact area for contacting a fluidic sample, and wherein at a closed configuration the plates sandwich a sample to be analyzed into a layer, that has a thickness 200 um or less, and has an sample area at last 100 times larger than the sample thickness; ii. the plurality of spacers have a predetermined substantially uniform height that is equal to or less than 200 microns, wherein at least one of the spacers is inside the sample contact area; iii. the clamp has two operation modes:
(a) a non-active mode, wherein the top ring and the bottom ring of the clamp do not push the first plate and second plate together; and
(b) an active mode, wherein the top ring and the bottom ring of the clamp are configured to exert a force to (i) squeeze the first plate and the second plate and deform the area of the flexible plates that is under the compression of the clamp, and (ii) deform the spacers that are under the compression of the clamp and crush at least one of the spacers, thereby reducing the spacing between the two plates in that area, and wherein the reduction of the plate spacing reduces or prevents a fluidic flow between a sample portion encircled by the rings and a sample portion outside the rings,
wherein in the open configuration the two plates are partially or completely separated apart, the spacing between the plates is not regulated by the spacers, and the clamp is in non-active mode, and the sample is deposited on one or both of the plates; and wherein in the closed configuration, at least a part of the sample deposited in the open configuration is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is regulated by the plates and the spacers.

2 . A device for fluidically isolating a portion of a sample and providing a rapid temperature change in the portion, comprising: a first plate, a second plate, a plurality of spacers, and a clamp, wherein:
i. the first plate and the second plate are movable relative to each other into different configurations, including an open configuration and a closed configuration, wherein one or both of the plates is flexible, wherein at least on plate has a thickness of 300 um or less, wherein each of the plates comprises, on its respective surface, a sample contact area for contacting a fluidic sample, and wherein at a closed configuration the plates sandwich a sample to be analyzed into a layer that has a thickness 200 um or less, and layer has an sample area at last 100 times larger than the sample thickness; ii. the plurality of spacers have a predetermined substantially uniform height that is equal to or less than 200 microns, wherein at least one of the spacers is inside the sample contact area; iii. the plates have a thin thickness that are configured to rapidly change the temperature of the sample; and iv. the clamp has two operation modes:
(a) a non-active mode, wherein the top ring and the bottom ring of the clamp do not push the first plate and second plate together; and
(b) an active mode, wherein the top ring and the bottom ring of the clamp apply a force to (i) squeeze the first plate and the second plate and deform the area of the flexible plates that is under the compression of the clamp, and (ii) deform the spacers that are under the compression of the clamp and crush at least one of the spacers, thereby reducing the spacing between the two plates in that area, and wherein the reduction of the plate spacing reduces or prevents a fluidic flow between a sample portion encircled by the rings and a sample portion outside the rings,
wherein in the open configuration the two plates are partially or completely separated apart, the spacing between the plates is not regulated by the spacers, the clamp is in non-active mode, and the sample is deposited on one or both of the plates; and wherein in the closed configuration, at least a part of the sample deposited in the open configuration is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is regulated by the plates and the spacers.

3 . The device of any prior claim, wherein the first plate or the second plate have a thickness less than or equal to 100 μm.

4 . The device of any prior claim, wherein both the first plate and the second plate have a thickness less than or equal to 100 μm.

5 . The device of any prior claim, further comprises a heating/cooling layer disposed on the exterior of either the first plate or the second plate, wherein the heating/cooling layer is configured to receive electromagnetic radiation.

6 . The device of any prior claim, wherein the heating/cooling layer disposed on the exterior of either the first plate or the second plate, the heating/cooling layer has a conductance of 6×10 −5 W/K or higher.

7 . The device of any prior claim, wherein the heating/cooling layer disposed on the exterior of either the first plate or the second plate, the heating/cooling layer has a conductance of from 6×10 −5 W/K to 1.5×10 −4 W/K.

8 . A device for rapidly changing the temperature of a thin fluidic sample layer with image monitoring, comprising:
i. any prior device; ii. a heater, and iii. an imager; wherein the imager images an area of the sample and a portion of the plates in the area, and the imager is configured to characterize a process of a rapid temperature change of the sample.

9 . A device for qPRC, comprising:
i. any prior device; ii. a heater; and iii. an imager for detecting a label; wherein the imager images an area of the sample and a portion of the plates in the area.

10 . The device of any prior claim, wherein the ring is circular, oval, rectangular, pentagonal, hexagonal, square, star, or any combination thereof with optional rounded corners.

11 . The device of any prior claim, wherein the plates and the clamp are configured to change the temperature of the sample at a rate of 10° C./s or higher.

12 . The device of any prior claim, wherein activation of the clamp exerts a pressure of 0.01 kg/cm{circumflex over ( )}2 or higher on the plates.

13 . The device of any prior claim, wherein the clamp comprises a top ring on the first plate and a bottom ring on the second plate that are movable toward each other.

14 . The device of any prior claim, wherein the first and/or second plate comprises a well and in the closed configuration the flow of sample from the inside to the outside of the well during thermal cycling or temperature changing is reduced compared to without using a clamping structure.

15 . The device of any prior claim, wherein the plurality of clamps, each reduce the flow of the sample from the inside to the outside of the ring area during thermal cycling or temperature changing.

16 . The device of any prior claim, wherein the plurality of clamps comprises at least 2, at least 4, at least 8, at least 16, at least 32 or at least 64 or more, top and bottom clamp rings, where the top rings are movable relative to the bottom rings, and when the plates are in the closed position the rings oppose each other and pinch different areas of the device to produce multiple isolated reaction chambe

Assignees

• Essenlix Corp

Inventors

• Chou Stephen
• Ding Wei
• Qi Ji
• Tan Hua
• Zhang Yufan

Classifications

• B01L2300/0851

  Bottom walls · CPC title

• B01L2200/10

  Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept · CPC title

• B01L2200/021

  Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry · CPC title

• B01L3/502738

  characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746) · CPC title

• B01L2300/123

  Flexible; Elastomeric · CPC title