Cartridge, electrowetting sample processing system and droplet formation

Abstract

A cartridge for use in an electrowetting sample processing system, the cartridge having at least one inlet port for introducing an input liquid in an internal gap of the cartridge, wherein the gap has at least one hydrophobic surface and is configured to provide an electrowetting induced movement of a microfluidic droplet of input liquid, wherein the input liquid has a carrier liquid and a processing liquid and the gap has a capture zone that is configured to capture at least a part of the processing liquid as a microfluidic droplet by use of electrowetting force and the gap further has a transfer zone that is configured to provide a passage for the carrier liquid next to the microfluidic droplet, while processing liquid is captured in the capture zone.

1 : A cartridge ( 2 ), in particular a disposable cartridge for use in an electrowetting sample processing system, the cartridge ( 2 ) comprising at least one inlet port ( 19 ′) for introducing an input liquid ( 60 , 61 ) in an internal gap ( 6 ) of the cartridge ( 2 ), wherein the gap ( 6 ) comprises at least one hydrophobic surface ( 17 ) and is configured to provide an electrowetting induced movement of a microfluidic droplet ( 23 ) of input liquid ( 60 , 61 ),
 wherein the input liquid ( 60 , 61 ) comprises a carrier liquid ( 60 ) and a processing liquid ( 61 ) and the gap ( 6 ) comprises a capture zone ( 62 ) that is configured to capture at least a part of the processing liquid ( 60 , 61 ) as a microfluidic droplet ( 23 ) by use of electrowetting force and the gap ( 6 ) further comprises a transfer zone ( 63 ) that is configured to provide a passage for the carrier liquid ( 60 ) next to the microfluidic droplet ( 23 ), while processing liquid ( 61 ) is captured in the capture zone ( 62 ). 
 
     
     
         2 : The cartridge according to  claim 1 , comprising a first part ( 4 ) with the inlet port ( 19 ′) and a second part ( 3 ) attached to the first part, such that the gap ( 6 ) is formed between the first part and the second part. 
     
     
         3 : The cartridge according to  claim 2 , wherein the first part ( 4 ) comprises a rigid body and/or the second part ( 3 ) comprises or is an electrode support element ( 11 ′) or a flexible film ( 3 ′), in particular a polymer film and/or an electrically isolating film. 
     
     
         4 : The cartridge according to  claim 2 , wherein the gap ( 6 ) is defined by a spacer ( 5 ) that is arranged between the first part and the second part and/or by the shape of at least one of the two parts of the cartridge, in particular by a flexible part or a rigid part of the cartridge, and wherein in particular the second part is attached to a peripheral side structure of the first part. 
     
     
         5 : The cartridge according to  claim 1 , comprising at least one electrode ( 10 ), in particular an electrode array ( 9 ), for applying an electrowetting force to the microfluidic droplet ( 23 ). 
     
     
         6 : The cartridge according to  claim 1 , comprises an inlet channel ( 19 ″) for transferring the processing liquid from the inlet port ( 19 ′) to the gap ( 6 ), wherein in particular the inlet channel ( 19 ″) is arranged substantially perpendicular or parallel to the orientation of the gap. 
     
     
         7 : The cartridge according to  claim 1 , comprises an inlet channel ( 19 ″) for transferring the processing liquid from the inlet port ( 19 ′) to the gap ( 6 ), wherein in particular the inlet channel ( 19 ″) is arranged substantially perpendicular or parallel to the orientation of the gap. 
     
     
         8 : The cartridge according to  claim 1 , configured to capture the processing liquid ( 61 ), which comprises at least one of: a reagent liquid, a buffer, a diluent, an extraction liquid, a washing liquid and a suspension, which further in particular is a suspension of magnetic beads, single cells or cell aggregates. 
     
     
         9 : The cartridge to  claim 1 , configured to be operated with a carrier liquid ( 60 ) that is a carrier liquid, in particular an electrowetting filler liquid, further in particular a silicone oil. 
     
     
         10 : The cartridge according to  claim 1 , configured to receive the input liquid ( 60 , 61 ), in which the carrier liquid ( 60 ) sequentially and/or alternatingly encloses the processing liquid ( 61 ). 
     
     
         11 : The cartridge according to  claim 1 , configured to provide the transfer zone ( 63 ) by an open space, which is located between the inlet port ( 19 ′) and the top of the microfluidic droplet ( 23 ) captured in the capture zone ( 62 ). 
     
     
         12 : The cartridge according to  claim 1 , comprising at least one capture zone ( 63 ) that is located closest to the inlet port ( 19 ′) such that the area of the capture zone covers between 5% and 95% of the opening area of the inlet port ( 19 ′), in particular between 10% and 90%, further in particular between 25% and 75%. 
     
     
         13 : The cartridge according to  claim 1 , comprising at least one capture electrode that is located closest to the inlet port ( 19 ′) such that the area of the capture electrode covers between 5% and 95% of the opening area of the inlet port ( 19 ′), in particular between 10% and 90%, further in particular between 25% and 75%. 
     
     
         14 : The cartridge according to  claim 1 , configured to receive the processing liquid ( 61 ) that comprises multiple parts, in particular parts of different compositions, and to accumulate these parts for providing the microfluidic droplet. 
     
     
         15 : The cartridge according to  claim 1 , configured to receive at least one part of the processing liquid ( 61 ) that comprises a volume that is insufficient for a transportation by electrowetting and/or that comprises a volume of less than 2 μl, in particular less than 1.5 μl. 
     
     
         16 : The cartridge according to  claim 1 , configured to capture or to accumulate a microfluidic droplet ( 23 ) of less than 10 μl in volume, in particular of less than 3 μl in volume. 
     
     
         17 : The cartridge according to  claim 1 , wherein the inlet port ( 19 ′) comprises a sealing surface ( 82 ) for a tube ( 51 ) to be inserted into the inlet port ( 19 ′), wherein in particular the inlet port ( 19 ′) is funnel-shaped with an enlarged opening towards the tube ( 51 ) to be inserted. 
     
     
         18 : An electrowetting sample processing system ( 1 ), in particular a biological sample processing system comprising a cartridge ( 2 ) according to  claim 1 . 
     
     
         19 : An electrowetting sample processing system ( 1 ) comprising at least one inlet port ( 19 ′) for introducing an input liquid and an internal gap ( 6 ) that comprises at least one hydrophobic surface ( 17 ) and
 that is configured to manipulate a microfluidic droplet ( 23 ) separated from the input liquid ( 60 , 61 ), if an electrowetting force is applied to the at least one microfluidic droplet, 
 wherein the input liquid comprises a processing liquid ( 61 ) and a carrier liquid ( 60 ) and the gap comprises a capture zone ( 62 ) that is configured to capture at least a part of the processing liquid by use of electrowetting force and the gap further comprises a transfer zone ( 63 ) that is configured to provide a passage for the carrier liquid from the inlet port to the gap, while processing liquid is captured in the capture zone. 
 
     
     
         20 : The electrowetting sample processing system according to  claim 18 , comprising at least one electrode ( 10 ), in particular an electrode array ( 9 ), for applying an electrowetting force to the processing liquid and/or the microfluidic droplet ( 23 ). 
     
     
         21 : The electrowetting sample processing system according to  claim 20 , wherein at least one electrode ( 10 ) comprises at least one capture electrode ( 62 ′) that is configured to capture at least a part of the processing liquid as a microfluidic droplet by use of electrowetting force, wherein in particular the edge of the capture electrode is arranged with an offset from the axis of flow of the inlet port ( 19 ′), further in particular with an offset of at least a quarter or at least half of a largest diameter of the capture electrode. 
     
     
         22 : The electrowetting sample processing system according to  claim 21 , wherein the one of the at least one capture electrode ( 62 ′) located closest to the inlet port ( 19 ′) covers between 5% and 95% of the opening area of the inlet port ( 19 ′), in particular between 10% and 90%, further in particular between 25% and 75%. 
     
     
         23 : The electrowetting sample processing system according to  claim 20 , wherein the at least one electrode ( 10 ) comprises a transport electrode ( 10 ′) for removing the microfluidic droplet from the capture zone. 
     
     
         24 : The electrowetting sample processing system according to  claim 18 , comprising a liquid feeder ( 50 ) that is operatively connected to the inlet port ( 19 ′) by a tube ( 51 ), in particular a flexible tube, for feeding an input liquid ( 60 , 61 ) of predetermined volume to the inlet port. 
     
     
         25 : The electrowetting sample processing system according to  claim 24 , wherein the liquid feeder ( 50 ) is configured to provide the input liquid ( 60 , 61 ) as at least one sequential and/or alternating feed of the processing liquid ( 61 ) and the carrier liquid ( 60 ). 
     
     
         26 : The electrowetting sample processing system according to  claim 18 , comprises a detector ( 70 , 71 ) for monitoring the feed of the input liquid ( 60 , 61 ), in particular the processing liquid ( 61 ) and/or the carrier liquid ( 60 ). 
     
     
         27 : The electrowetting sample processing system according to  claim 18 , comprises a controller for operating the liquid feeder ( 50 ), in particular a droplet generator, independently and/or asynchronously from the operation of electrodes used for electrowetting. 
     
     
         28 : A method for operating the cartridge or the sample processing system according to  claim 18 . 
     
     
         29 : A method for operating a cartridge ( 2 ) that comprises at least one inlet port ( 19 ′) and an internal gap ( 6 ) with a capture zone ( 62 ) and a transfer zone ( 63 ), the method comprising:
 providing an input liquid ( 60 , 61 ) that comprises a processing liquid ( 61 ) and a carrier liquid ( 60 ); 
 separating at least a part of the processing liquid ( 61 ) in the capture zone ( 62 ) by use of electrowetting force; 
 transferring the carrier liquid ( 60 ) from the inlet port ( 19 ′) to the gap ( 6 ) via the transfer zone ( 63 ), while the processing liquid ( 61 ) is captured in the capture zone ( 62 ); and 
 capturing at least a part of the processing liquid ( 61 ) in the capture zone ( 62 ) for providing a microfluidic droplet ( 23 ) that is movable by applying an electrowetting force to the microfluidic droplet ( 23 ). 
 
     
     
         30 : The method according to the  claim 28 , wherein the step of providing the input liquid ( 60 , 61 ) is accomplished by sequentially and/or alternatingly feeding the processing liquid ( 61 ) and the carrier liquid ( 60 ). 
     
     
         31 : The method according to  claim 28 , wherein the input liquid ( 60 , 61 ) comprises multiple liquid parts, in particular parts of different compositions, and the capturing is accomplished by accumulating these parts for providing the microfluidic droplet ( 23 ). 
     
     
         32 : The method according to  claim 31 , wherein the input liquid ( 60 , 61 ) comprises at least one part that comprises a volume that is insufficient for a transportation by electrowetting and/or that comprises a volume of less than 2 μl, in particular less than 1.5 μl. 
     
     
         33 : The method according to  claim 28 , comprising sequentially actuating electrodes for inducing a motion of the microfluidic droplets away from the capture zone ( 62 ), thereby enabling a following part of the processing liquid ( 61 ) to be captured.