# US 8,541,176 B2 · Droplet-based surface modification and washing

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- Number: US 8,541,176 B2
- Document ID: US8541176B2
- Status: Granted
- Kind: B2
- Application number: 12/113,385
- Filed: 2008-05-01
- Published: 2012-06-28
- Granted: 2013-09-24
- Earliest claimed: 2006-04-18
- Assignees: Advanced Liquid Logic, Inc.; Duke University
- Applicants: Vamsee K. Pamula; Vijay Srinivasan; Allen E. Eckhardt; Michael G. Pollack; Richard B. Fair
- Inventors: Vamsee K. Pamula; Vijay Srinivasan; Allen E. Eckhardt; Michael G. Pollack; Richard B. Fair
- Web page: https://patentgrep.com/patent/US8541176B2

## CPC

- G01N 27/26: by investigating electrochemical variables; by using electrolysis or electrophoresis
- B01F 33/3021: {the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets}
- B01F 33/3031: using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502723: {characterised by venting arrangements}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B01L 3/502792: {for moving individual droplets on a plate, e.g. by locally altering surface tension}
- B01L 7/525: {with physical movement of samples between temperature zones}
- C12Q 1/686: Polymerase chain reaction [PCR]
- C12Q 1/6869: Methods for sequencing
- G01N 27/3271: {Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood (amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001)}
- G01N 27/416: Systems (G01N27/27 takes precedence)
- G01N 27/447: using electrophoresis
- G01N 35/00029: {provided with flat sample substrates, e.g. slides (G01N35/028 takes precedence)}
- B01L 3/0268: {using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries}
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B01L 2200/027: for microfluidic devices
- B01L 2200/0668: Trapping microscopic beads
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2300/0654: Lenses; Optical fibres
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0861: Configuration of multiple channels and/or chambers in a single devices
- B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2300/089: Virtual walls for guiding liquids
- B01L 2300/1827: using resistive heater
- B01L 2400/0406: capillary forces
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/0424: Dielectrophoretic forces
- B01L 2400/0427: Electrowetting
- B01L 2400/043: magnetic forces
- B01L 2400/0436: acoustic forces, e.g. surface acoustic waves [SAW]
- B01L 2400/0442: thermal energy, e.g. vaporisation, bubble jet
- B01L 2400/0448: Marangoni flow; Thermocapillary effect
- G01N 2035/00158: {Elements containing microarrays, i.e. "biochip"}
- G01N 2035/00237: {Handling microquantities of analyte, e.g. microvalves, capillary networks}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of modifying a surface on a droplet microactuator is provided, wherein the method includes executing one or more droplet operations to bring a droplet comprising a surface-modifying agent into contact with the surface. According to another embodiment, a droplet microactuator is provided and includes a sample or reagent immobilized on a surface thereof and arranged such that a droplet on the droplet microactuator may contact the surface. According to yet another embodiment, a method of removing a substance from a surface to which the substance is bound is provided, the method including conducting one or more droplet operations to contact a droplet with the surface, the droplet comprising a solution for eluting the substance from the surface

## Claims

### Claim 1

A droplet microactuator comprising:
(a) an oil filler fluid;
(b) one or more electrodes arranged to conduct electrowetting-mediated droplet operations; and
(c) a substance immobilized on a surface of the droplet microactuator, in contact with the oil filler fluid, and arranged such that a droplet on the droplet microactuator in the oil filler fluid may contact the surface via electrowetting-mediated droplet operations and thereby reduce the quantity of the substance in contact with the surface.

### Claim 2 (depends on 1)

The droplet microactuator of claim 1 wherein the surface is arranged such that the droplet may contact the surface during a droplet operation.

### Claim 3 (depends on 1)

The droplet microactuator of claim 1 wherein the substance is selected from the group consisting of proteins and peptides.

### Claim 4 (depends on 1)

The droplet microactuator of claim 1 wherein the substance is selected from the group consisting of antibodies and antigens.

### Claim 5 (depends on 1)

The droplet microactuator of claim 1 wherein the substance is selected from the group consisting of nucleic acids.

### Claim 6 (depends on 1)

The droplet microactuator of claim 1 wherein the substance comprises a dried sample or reagent.

### Claim 7

A droplet microactuator comprising:
(a) an oil filler fluid;
(b) one or more electrodes arranged to conduct electrowetting-mediated droplet operations; and
(c) a substance immobilized on a surface of the droplet microactuator, in contact with the oil filler fluid, and arranged such that a droplet on the droplet microactuator in the oil filler fluid may contact the surface via electrowetting-mediated droplet operations and thereby reduce the quantity of the substance in contact with the surface, wherein the surface comprises a surface of one of a top plate or a bottom plate of the droplet microactuator.