Fluidic devices with freeze-thaw valves with ice-nucleating agents and related methods of operation and analysis

Patent metadata

Field	Value
Publication number	US-2018200720-A1
Application number	US-201615742662-A
Country	US
Kind code	A1
Filing date	Jul 22, 2016
Priority date	Jul 22, 2015
Publication date	Jul 19, 2018
Grant date	—

Abstract

Embodiments of the invention provide fluidic devices such as, but not limited to, microfluidic chips, with one or more freeze thaw valves (FTVs) employing one or more ice-nucleating agents (INAs), that can reliably operate to freeze at relatively higher temperatures and/or at faster rates than conventional microfluidic devices with FTV systems.

First claim

1 . A fluidic analysis device, comprising:
at least one fluid channel comprising at least one freeze thaw valve and at least one ice nucleating agent (INA), wherein the at least one INA is a carbon-containing INA.

2 . The fluidic analysis device of claim 1 , wherein the at least one INA comprises an ice-nucleating protein and/or a functional fragment thereof, an ice-nucleating nucleic acid, an ice-nucleating lipid, and/or an ice-nucleating carbohydrate.

3 . The fluidic analysis device of claim 1 , wherein the at least one INA is extracted or derived from an organism.

4 . The fluidic analysis device of claim 1 , wherein the at least one INA comprises an ice-nucleating protein (INP) and/or a functional fragment thereof.

5 . The fluidic analysis device of claim 4 , wherein the INP and/or the functional fragment thereof is encoded by a gene selected from the group consisting of: iceE, iceH, inaA, inaE, inaF, inaK, inaPb, inaQ, inaU, inaV, inaW, inaX, and inaZ, and wherein the gene is found in or obtained from an organism selected from the group consisting of: Pseudomonas syringae , Ps. fluorescens KUIN-1 , Erwinia herbicola, E. uredovora, Pantoea ananatis, Xanthomonas campestris, E. carotovora , Ps. antarctica , Ps. aeruginosa , Ps. putida , Ps. viridiflava , Pa. agglomerans, E. ananas , and/or Ps. borealis.

6 . The fluidic analysis device of claim 1 , further comprising first and second substrates attached together to define a microfluidic chip as the fluid analysis device with the at least one fluid transport channel and a plurality of spaced apart freeze thaw valves along the at least one fluid transport channel as the at least one freeze thaw valve.

7 . The fluidic analysis device of claim 1 , in fluid communication with a liquid buffer comprising the at least one INA, wherein the at least one INA is flowably introduced into a fluid port on the fluidic analysis device.

8 . The fluidic analysis device of claim 1 , wherein the at least one freeze thaw valve is a plurality of spaced apart freeze thaw valves, each comprising a thermoelectric cooler in thermal communication with a defined region of the at least one fluid channel, and wherein the at least one fluid channel has at least a segment that is sized to be a microfluidic or nanofluidic channel.

9 . The fluidic analysis device of claim 1 , wherein the at least one fluid channel comprises a primary transport channel and at least one reagent channel, and wherein the fluidic analysis device comprises a sample input, a buffer input and a bead well array, all in fluid communication with the primary transport channel, with the at least one freeze thaw valve comprising a plurality of spaced apart freeze thaw valves in fluid communication with the primary transport channel and/or at least one reagent channel.

10 . The fluidic analysis device of claim 1 , wherein the at least one fluid channel comprises at least one fluid channel with the at least one INA bonded and/or coated to a surface thereof.

11 . The fluid analysis device of claim 9 , further comprising a bead storage/sample incubation chamber, a waste reservoir and a sample metering loop, the sample metering loop residing between the bead storage/incubation chamber and the sample input, wherein the sample metering loop has a volumetric capacity of between about 1 μL to about 1 mL and is in fluid communication with first and second freeze thaw valves on respective end portion of the sample metering loop.

12 . The fluid analysis device of claim 1 , wherein the at least one INA may comprise a structure similar to ice and/or a structure that aligns water molecules into an ice-like lattice.

13 . A method of analyzing a target analyte, comprising:
providing a fluidic analysis device with at least one fluidic channel in fluid communication with at least one freeze thaw valve; introducing at least one ice nucleating agent (INA) into the at least one fluidic channel, wherein the at least one INA contains a carbon atom; and electronically selectively cooling the at least one freeze thaw valve to freeze the at least one freeze thaw valve using the at least one INA.

14 . The method of claim 13 , wherein the at least one freeze thaw valve is a plurality of spaced apart freeze thaw valves, and wherein the method comprises setting coolers thermally communicating with the at least one fluidic channel to a temperature between −100 degrees C. and −1 degree C. to freeze the freeze thaw valves.

15 . The method of claim 13 , wherein the fluidic device is a fluidic microchip with a thickness between 0.1 mm and 10 mm, wherein the at least one freeze thaw valve is a plurality of spaced apart freeze thaw valves, and wherein at least some of the freeze thaw valves have thermoelectric coolers set to between about −100 degrees C. and about −1 degree C. for a freeze operation that occurs in three minutes or less, and wherein the electronically selectively cooling is carried out a plurality of times for a respective sample.

16 . The method of claim 13 , wherein the device is a fluidic microchip, and wherein the analyte is an organic molecule, elemental compound, inorganic compound, pharmaceutical, DNA, RNA, peptide, protein, glycan, or other biological or synthetic macromolecule.

17 . The method of claim 13 , wherein the at least one INA comprises an ice-nucleating protein and/or a functional fragment thereof, an ice-nucleating nucleic acid, an ice-nucleating lipid, and/or an ice-nucleating carbohydrate.

18 . The method of claim 13 , wherein the at least one INA is extracted or derived from an organism.

19 . The method of claim 13 , wherein the at least one INA comprises an ice-nucleating protein (INP) and/or a functional fragments thereof.

20 . The method of claim 19 , wherein the INP and/or the functional fragment thereof is encoded by a gene selected from the group consisting of: iceE, iceH, inaA, inaE, inaF, inaK, inaPb, inaQ, inaU, inaV, inaW, inaX, and inaZ, and wherein the gene is found in or obtained from an organism selected from the group consisting of: Pseudomonas syringae , Ps. fluorescens KUIN-1 , Erwinia herbicola, E. uredovora, Pantoea ananatis, Xanthomonas campestris, E. carotovora , Ps. antarctica , Ps. aeruginosa , Ps. putida , Ps. viridiflava , Pa. agglomerans, E. ananas , and/or Ps. borealis.

21 . The method of claim 13 , wherein the at least one INA is flowably introduced into the at least one fluidic channel in a liquid.

22 . The method of claim 21 , wherein the liquid is a buffer, and wherein the at least one INA is diluted in the buffer.

23 . The method of claim 13 , wherein the at least one INA is introduced from a surface comprising a coating of the at least one INA and/or the at least one INA is adsorbed and/or chemically bonded to a surface of the at least one fluidic flow channel.

24 . The method of claim 13 , wherein the at least one INA is immobilized on or coupled to a solid support.

25 . The method of claim 13 , wherein the at least one INA may comprise a structure similar to ice and/or a structure that aligns water molecules into an ice-like lattice.

26 . A liquid buffer for DNA processing comprising at least one ice nucleating agent (INA), wherein the at least one INA contains a carbon atom, and optionally wherein the at least one INA is present in the liquid buffer in an amount between 1 molecule/μL and 10 billion molecules/μL and/or in a concentr

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Ramsey John Michael
• Henley William Hampton
• Gaiteri Joseph Carl

Classifications

• C12N15/115

  Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers} · CPC title

• F16K99/0044 Primary

  using thermo-electric means · CPC title

• B01L7/50 Primary

  Cryostats · CPC title

• F16K2099/0084

  Chemistry or biology, e.g. "lab-on-a-chip" technology · CPC title

• F16K99/0032

  using phase transition or influencing viscosity · CPC title