Bead separation in microfluidics

Patent metadata

Field	Value
Publication number	US-2018339923-A1
Application number	US-201615756209-A
Country	US
Kind code	A1
Filing date	Sep 1, 2016
Priority date	Sep 2, 2015
Publication date	Nov 29, 2018
Grant date	—

Abstract

Digital microfluidics system with electrodes attached to a PCB has control unit for manipulating liquid droplets by electrowetting, cartridge accommodation site for taking up a disposable cartridge having a working gap in-between two hydrophobic surfaces, and magnetic conduit/backing combination. A barrier element on an individual electrode of the PCB for narrowing the working gap. A disposable cartridge is positioned at the cartridge accommodation site, its flexible working film touching there and of the barrier element an uppermost surface. In the working gap and above a path of selected electrodes a liquid portion or liquid droplet with magnetically responsive beads moves by electrowetting on the electrode path until a magnetic field of the magnetic conduit is reached. The backing magnet is activated before and during the moving to thereby attract and remove magnetically responsive beads therefrom.

First claim

1 . A method of substantially removing magnetically responsive beads from liquid portions or droplets in digital microfluidics,
wherein the method comprises the steps of: a) providing a digital microfluidics system ( 1 ) comprising: a number or array of individual electrodes ( 2 ) attached to a first substrate or PCB ( 3 );
a central control unit ( 7 ) in operative contact with said individual electrodes ( 2 ) for controlling selection and for providing a number of said individual electrodes ( 2 ) that define a path of individual electrodes ( 2 ′) with voltage for manipulating liquid portions ( 8 - 2 ) or liquid droplets ( 8 - 1 ) by electrowetting;
a cartridge accommodation site ( 18 ) that is configured for taking up a disposable cartridge ( 17 ) which comprises a first hydrophobic surface ( 5 ) that belongs to a flexible working film ( 19 ), a second hydrophobic surface ( 6 ) that belongs to a cover plate ( 20 ) of the disposable cartridge ( 17 ), and a working gap ( 4 ) that is located in-between the two hydrophobic surfaces ( 5 , 6 ); and
at least one magnetic conduit ( 9 ) located in the first substrate or PCB ( 3 ) of the microfluidics system ( 1 ) and below said individual electrodes ( 2 ), said at least one magnetic conduit ( 9 ) being backed by a backing magnet ( 10 ) with a magnetic field, being configured for directing said magnetic field through the magnetic conduit ( 9 ) to the first hydrophobic surface ( 5 ) on said individual electrodes ( 2 ), and being located in close proximity to individual electrodes ( 2 );
b) providing at least one barrier element ( 40 ) and positioning said barrier element ( 40 ) at least partially on an individual operating electrode ( 2 ) located at the cartridge accommodation site ( 18 ) of the PCB ( 3 ), the barrier element ( 40 ) narrowing the working gap ( 4 ) of a disposable cartridge ( 17 ) situated on a surface of said cartridge accommodation site ( 18 ); c) providing a disposable cartridge ( 17 ) and positioning said disposable cartridge ( 17 ) at a cartridge accommodation site ( 18 ) of said digital microfluidics system ( 1 ); the flexible working film ( 19 ) comprising a backside ( 21 ) that, when the disposable cartridge ( 17 ) is accommodated on said cartridge accommodation site ( 18 ), touches an uppermost surface ( 22 ) of the cartridge accommodation site ( 18 ) of the digital microfluidics system ( 1 ) and of said at least one barrier element ( 40 ); d) providing on the hydrophobic surface ( 5 ) and above a path of selected electrodes ( 2 ′) at least one liquid portion ( 8 - 2 ) or liquid droplet ( 8 - 1 ) that comprises magnetically responsive beads ( 11 ); e) moving by electrowetting said at least one liquid portion ( 8 - 2 ) or liquid droplet ( 8 - 1 ) with the magnetically responsive beads ( 11 ) on said path of selected electrodes ( 2 ′) until said magnetic field of the at least one magnetic conduit ( 9 ) backed by a backing magnet ( 10 ) is reached; and f) activating said backing magnet ( 10 ) before and during moving by electro-wetting said at least one liquid portion ( 8 - 2 ) or liquid droplet ( 8 - 1 ) with the magnetically responsive beads ( 11 ) on said path of selected electrodes ( 2 ′) and over and/or around said at least one barrier element ( 40 ), thereby attracting and substantially removing magnetically responsive beads ( 11 ) from said liquid portion ( 8 - 2 ) or liquid droplet ( 8 - 1 ).

2 . The removing method of claim 1 ,
wherein using a vacuum source ( 23 ) of the digital microfluidics system ( 1 ), an underpressure is established in an evacuation space ( 24 ) between the uppermost surface ( 22 ) of the cartridge accommodation site ( 18 ) and the backside ( 21 ) of the flexible working film ( 19 ) of the disposable cartridge ( 17 ), whereupon the flexible working film ( 19 ) of the disposable cartridge ( 17 ) spreads on the uppermost surface ( 22 ) of the cartridge accommodation site ( 18 ) of the digital microfluidics system ( 1 ) and over said at least one barrier element ( 40 ).

3 . The removing method of claim 1 ,
wherein using a filler-fluid or other fluid, an overpressure is established within the working gap ( 4 ) of the disposable cartridge ( 17 ), whereupon the flexible working film ( 19 ) of the disposable cartridge ( 17 ) spreads on the uppermost surface ( 22 ) of the cartridge accommodation site ( 18 ) of the digital microfluidics system ( 1 ) and over said at least one barrier element ( 40 ).

4 . The removing method of claim 2 ,
wherein the cover plate ( 20 ) of the disposable cartridge ( 17 ) is configured as a rigid cover plate, evenly defining a top of said working gap ( 4 ).

5 . The removing method of claim 1 ,
wherein said at least one magnetic conduit ( 9 ) consists of a single solid ferromagnetic element, or of a multitude of randomly orientated ferromagnetic elements, or of an amorphous paste filled with ferromagnetic material.

6 . The removing method of claim 5 ,
wherein said at least one magnetic conduit ( 9 ) is located under and is covered by an individual electrode ( 2 ).

7 . The removing method of claim 5 ,
wherein said at least one magnetic conduit ( 9 ) is located beside of and is not covered by at least one individual electrode ( 2 ).

8 . The removing method of claim 5 ,
wherein said backing magnet ( 10 ) is used to operatively back at least one magnetic conduit ( 9 ) and is configured as a permanent magnet ( 10 ′), or as a switchable permanent magnet ( 10 ″), or as an electromagnet ( 10 ′″).

9 . The removing method of claim 8 ,
wherein actuating said backing magnet ( 10 ) is achieved by: a) moving a permanent magnet ( 10 ′) to a backside of the at least one magnetic conduit ( 9 ); or b) switching-on a switchable permanent magnet ( 10 ″) that is located at the backside of the at least one magnetic conduit ( 9 ); or c) energizing an electromagnet ( 10 ′″) that is located at the backside of the at least one magnetic conduit ( 9 ).

10 . The removing method of claim 9 ,
wherein switching-on a switchable permanent magnet ( 10 ″) is carried out by switching-off an electromagnet ( 33 ) that is compensating the magnetic field of a PE-magnet ( 32 ).

11 . The removing method of claim 1 ,
wherein said at least one magnetic conduit ( 9 ) is a cylindrical, cuboid, pyramidal, frustoconical, conical, or magnetic conduit ( 9 ′, 9 ″) located in a blind hole ( 15 ) or in a through hole ( 16 ) in the first substrate ( 3 ) of the digital microfluidics system ( 1 ).

12 . The removing method of claim 1 ,
wherein the cartridge accommodation site ( 18 ) of the digital microfluidics system ( 1 ) or the disposable cartridge ( 17 ) comprise a gasket ( 27 ), using which said evacuation space ( 24 ) is sealingly enclosed and a height ( 28 ) of the working gap ( 4 ) between said hydrophobic surfaces ( 5 , 6 ) of the disposable cartridge ( 17 ) is defined.

13 . The removing method of claim 1 ,
wherein the cartridge accommodation site ( 18 ) of the digital microfluidics system ( 1 ) comprises at least one check valve ( 42 ), using which said working gap is sealingly closed and an overpressure produced by a filler fluid or other fluid inside said working gap is enabled.

14 . A method of substantially suspending magnetically responsive beads in liquid portions or droplets in digital microfluidics,
wherein the method comprises the steps of: a) providing a digital microfluidics system ( 1 ) comprising
a number or array of individual electrodes ( 2 ) attached to a first substrate or PCB ( 3 ),
a central control unit ( 7 ) in operative contact with said individual electrodes ( 2 ) for controlling selection and for p

Assignees

• Tecan Trading Ag

Inventors

• Perroud Thomas
• Tran Dan
• Hoffmeyer Daniel
• Lay Tiffany
• Dhindsa Manjeet

Classifications

• B01L2300/123

  Flexible; Elastomeric · CPC title

• B01L3/502761

  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 · CPC title

• B01L2400/043

  magnetic forces · CPC title

• B01L3/50273

  characterised by the means or forces applied to move the fluids · CPC title

• B01L3/508

  Rigid containers without fluid transport within · CPC title