Method and apparatus for measuring phase transition characteristics of macromolecules
AssigneeCambridge Enterprise Limited
InventorsWilliam E. ARTER, Georg KRAINER, Timothy WELSH, Runzhang QI, Tuomas P.J. KNOWLES
Life of this patent
Estimating the term…
Abstract
A method measuring the phase transition characteristics of a macromolecule, the method comprising: generating a stream of micro-droplets comprising at least one constituent, of which one constituent comprises the macromolecule, varying the conditions in the micro-droplets; and measuring the relative concentrations of the constituents of, and the phases of the macromolecule present in, the micro-droplets.
Claims33
A method measuring the phase transition characteristics of a macromolecule, the method comprising:
- generating a stream of micro-droplets comprising at least one constituent, of which one constituent comprises the macromolecule,
- varying the conditions in the micro-droplets;
- and
- measuring the relative concentrations of the constituents of, and the phases of the macromolecule present in, the micro-droplets.
The method of any preceding claim, wherein the conditions in the micro-droplets are varied by varying the relative concentrations, in the micro-droplets, of the constituent comprising the macromolecule and at least one further constituent.
The method of any preceding claim, wherein the stream of micro-droplets is a continuous stream.
The method of claim any preceding claim, wherein the measuring is performed continuously on the stream of micro-droplets.
The method of any preceding claim, wherein the stream of micro-droplets is generated by injecting a stream of a first fluid comprising the constituents into a stream of a second fluid, the second fluid being immiscible with the first fluid.
The method of claim any preceding claim, wherein the relative concentrations of the constituents of the micro-droplets are varied by varying relative flow rates of the respective streams of the at least two constituents of the micro-droplets.
The method of any preceding claim, wherein the relative concentrations of the constituents of the micro-droplets are measured by a first optical means.
The method of any preceding claim, wherein the phases of the macromolecule present in the micro-droplets are measured by a second optical means.
The method of any preceding claim, wherein the relative concentrations of the constituents of the micro-droplets are varied based on the measured relative concentrations of the constituents of, and the phases of the macromolecule present in, the micro-droplets.
The method of any preceding claim, wherein the macromolecule comprises one or more of:
- a protein, and a nucleic acid.
The method of any preceding claim, wherein the at least two constituents further comprise one or more of:
- a pH buffer, a phase separator, a salt solution and a therapeutic drug/drug candidate.
A method of screening therapeutic drug candidates, the method comprising the steps of the method of any preceding claim, wherein at least one constituent of the micro-droplets, other than the macromolecule, comprises a drug candidate.
An apparatus for measuring phase transition characteristics of a macromolecule, the apparatus comprising:
- a microfluidics system configured to generate a stream of micro-droplets comprising at least one constituent, of which one constituent comprises the macromolecule, and vary the relative concentrations of the constituents of the micro-droplets and/or the temperature of the micro-droplets;
- and
- a first optical system configured to measure the relative concentrations of the constituents of the micro-droplets generated by the microfluidics system;
- and
- a second optical system configured to measure the phases of the macromolecule present in the micro-droplets generated by the microfluidics system.
The methods or apparatus of any one of any preceding claim, wherein the constituent comprising the macromolecule comprises one or more of:
- the macromolecule itself, a cell, a subcellular organelle, a cell lysate.
The methods or apparatus of any preceding claim, wherein the phase transition characteristics of two or more macromolecules are measured simultaneously, at least one constituent comprising a further macromolecule.
Dependencies are inferred from the claim text.