Nanoscale biochemical sample preparation and analysis

Patent metadata

Field	Value
Publication number	US-12005452-B2
Application number	US-202117404478-A
Country	US
Kind code	B2
Filing date	Aug 17, 2021
Priority date	Nov 7, 2016
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

First claim

What is claimed is:

1. A platform for biological sample preparation, comprising:
a substrate comprising at least one reactor vessel having one or more hydrophilic surfaces configured for containment of a biological sample, wherein the hydrophilic surface is formed on an upper surface of a pillar and defines the lateral boundary of the least one reactor vessel and the hydrophilic surfaces have a non-zero total surface area less than 25 mm 2 ;
a spacer containing an aperture, wherein the aperture is dimensioned to surround the at least one reactor vessel when the spacer is positioned on the substrate;
a cover positioned on the spacer; and
a membrane interposed between the spacer and the cover and the membrane overlies the spacer, wherein the membrane has a membrane aperture that is dimensioned to surround the at least one reactor vessel when the membrane is positioned on the spacer, wherein the substrate, spacer and cover are each formed from a material that is transparent to optical light.

2. The platform of claim 1 , wherein the substrate is formed from glass.

3. The platform of claim 1 , further comprising at least one hydrophobic surface surrounding the at least one reactor vessel.

4. The platform of claim 1 , further comprising at least two reactor vessels, wherein the at least two reactor vessels are separated by a hydrophobic surface.

5. The platform of claim 1 , wherein the hydrophilic surfaces of the at least one reactor vessel have a total surface area of less than 5 mm 2 .

6. The platform of claim 1 , wherein the hydrophilic surfaces of the at least one reactor vessel have a total surface area of less than 1 mm 2 .

Assignees

• Battelle Memorial Institute

Inventors

• Kelly Ryan T
• Zhu Ying
• Smith Richard D

Classifications

• B01J2219/00659

  Two-dimensional arrays · CPC title

• G01N33/68

  involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} · CPC title

• B01J2219/00317

  Microwell devices, i.e. having large numbers of wells · CPC title

• G01N33/4833

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• B01J19/0046

  Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays (synthesis methods per se C40B50/00) · CPC title