Systems and methods for handling and analyzing samples

Patent metadata

Field	Value
Publication number	US-2024326055-A1
Application number	US-202218579231-A
Country	US
Kind code	A1
Filing date	Jul 14, 2022
Priority date	Jul 15, 2021
Publication date	Oct 3, 2024
Grant date	—

Abstract

Methods and systems for handling and/or analyzing samples are provided. In one example, a method comprises: introducing (406), with a liquid handler (322), at least one assisting agent into a sample well (310) of a well plate (312), wherein the sample comprises a sample volume; and ejecting (408), with an acoustic droplet ejector, ADE, (306), a mixture comprising the sample mixed with the at least one assisting agent from the sample well, wherein the at least one assisting agent interacts (406) with an analyte of the sample to limit gel formation at a top surface of the sample volume, prior to the mixture ejection.

First claim

What is claimed is:

1 . A system for analyzing a sample, the system comprising:
a first plate handler; a liquid handler; an acoustic droplet ejector (ADE); an open port interface (OPI); a mass capture and analysis system; a processor operatively coupled to each of the first plate handler, the liquid handler, the ADE, the OPI, and the mass capture and analysis system; and memory, operatively connected to the processor, the memory storing instructions that, when executed by the processor, perform a set of operations comprising:
receiving, by the first plate handler, a well plate comprising a plurality of sample wells, each sample well configured to contain a sample having a sample volume;
introducing, by the liquid handler, at least one assisting agent into at least one sample well;
ejecting, with the ADE, a mixture comprising the sample and the at least one assisting agent from the at least one sample well and into the OPI for transport to the mass capture and analysis system; and
detecting, with the mass capture and analysis system, at least one analyte of the mixture.

2 . The system of claim 1 , further comprising a sample handler, wherein the set of operations further comprises introducing, with the sample handler, the sample into the at least one sample well.

3 . The system of claim 2 , wherein the set of operations further comprises introducing, with the liquid handler, the at least one assisting agent into the at least one sample well, at least one of:
before introduction of the sample to the at least one sample well, after introduction of the sample to the at least one sample well, and simultaneously with introduction of the sample to the at least one sample well.

4 . The system of claim 1 , wherein the mixture is transported from the OPI to the mass capture and analysis system via a transfer conduit.

5 . The system of claim 1 , wherein the set of operations further comprises introducing a transport liquid to the OPI, and wherein the mixture is diluted in the transport liquid during transport of the mixture to the mass capture and analysis system.

6 . The system of claim 1 , further comprising a housing at least partially enclosing the well plate.

7 . The system of claim 6 , further comprising a non-reactive gas source communicatively coupled to an interior of the housing, and wherein the set of operations further comprises:
introducing a non-reactive gas from the non-reactive gas source to the interior of the housing.

8 . (canceled)

9 . The system of claim 1 , further comprising a protector for selectively applying and removing a seal from the well plate.

10 . The system of claim 1 , wherein the liquid handler comprises at least one of an automatic pipetting robot, an automated dispensing device, and an acoustic dispenser.

11 . A method for handling a sample for analysis, the method comprising:
introducing, with a liquid handler, at least one assisting agent into a sample well of a well plate, wherein the sample comprises a sample volume; and ejecting, with an acoustic droplet ejector (ADE), a mixture comprising the sample mixed with the at least one assisting agent from the sample well, wherein the at least one assisting agent interacts with an analyte of the sample to limit gel formation at a top surface of the sample volume, prior to the mixture ejection.

12 . The method of claim 11 , further comprising introducing the sample into the sample well; wherein the at least one assisting agent prevents gel formation at the top surface of the sample volume, prior to the mixture ejection.

13 . (canceled)

14 . The method of claim 11 , further comprising:
supplying a non-reactive gas to isolate the sample well from reactive gas in ambient air; and ejecting the mixture from the sample well through the non-reactive gas.

15 . The method of claim 11 , wherein the at least one assisting agent is selected from the group consisting of: a reducing agent, an alkylation agent, a blocking agent, a buffer, an enzyme, a substrate, a co-factor, a stabilizer, a viscosity-modifying agent, and combinations thereof.

16 . The method of claim 11 , wherein the analyte comprises at least one biomolecule analyte having at least a S—S or a S—H group.

17 . The method of claim 16 , wherein the at least one assisting agent comprises a reducing agent capable of converting the S—S group into S—H group and/or preventing the S—H group from being oxidized or being coupled to another S—H group.

18 . The method of claim 16 , wherein the at least one assisting agent further comprises an alkylation agent capable of converting the S—H group into a more stable S—R group.

19 . The method of claim 16 , wherein the at least one assisting agent reduces inter-molecular coupling of the analyte through S—S formation.

20 . The method of claim 15 , wherein the at least one assisting agent comprises a reducing agent that is selected from the group consisting of: dithiothreitol (DTT), dithioerythritol (DTE), tris (2-carboxyethyl) phosphine hydrochloride (TCEP), 2-mercaptoethanol, 2-mercaptoethylamine, thioglycolic acid, cysteine, guanidine, urea, or any salt or derivative thereof, and combinations thereof.

21 . The method of claim 15 , wherein the at least one assisting agent comprises an alkylation agent that is selected from the group consisting of: iodoacetamide, iodoacetic acid, acrylamide, chloroacetamide, and combinations thereof.

22 . A system for analyzing a sample, the system comprising:
a first plate handler; a second plate handler; a liquid handler; an acoustic droplet ejector (ADE); a processor operatively coupled to each of the first plate handler, the second plate handler, the liquid handler and the ADE, and memory, operatively connected to the processor, the memory storing instructions that, when executed by the processor, perform a set of operations comprising: receiving, by the first plate handler, a well plate comprising a plurality of sample wells, each sample well configured to contain a sample having a sample volume; introducing, by the liquid handler, at least one assisting agent into at least one sample well; positioning via the second plate handler, an opposed sample well in relation to the at least one sample well; ejecting, with the ADE, a mixture comprising the sample and the at least one assisting agent from the at least one sample well and into the opposed sample well.

Assignees

• Dh Technologies Dev Pte Ltd

Inventors

• Covey Thomas R
• Liu Chang

Classifications

• H01J49/0431 Primary

  for liquid samples (interfaces to liquid chromatographs G01N30/7233) · CPC title

• B01L2400/0436

  acoustic forces, e.g. surface acoustic waves [SAW] · CPC title

• B01L2300/0829

  Multi-well plates; Microtitration plates · CPC title

• B01L2200/027

  for microfluidic devices · CPC title

• B01L2400/0439

  ultrasonic vibrations, vibrating piezo elements · CPC title