Cartridge and electrowetting sample processing system with delivery zone

Abstract

A cartridge, in particular a disposable cartridge, for use in an electrowetting sample processing system. The cartridge has a liquid input port for introducing an input liquid into an internal gap of the cartridge, the input liquid providing for at least one droplet, directly or via a liquid separation process within the internal gap, and the internal gap having at least one hydrophobic surface, at least one processing zone for processing samples located in the processing zone, and a delivery zone for delivering the at least one droplet from the liquid input port to the at least one processing zone. The delivery zone is configured to provide a repeating pattern of interacting electrowetting force for simultaneously transporting the at least one droplet within the delivery zone.

1 . A cartridge ( 2 ), in particular a disposable cartridge, for use in an electrowetting sample processing system ( 1 ), the cartridge ( 2 ) comprising a liquid input port ( 19 ′) for introducing an input liquid into an internal gap ( 6 ) of the cartridge ( 2 ), the input liquid providing for at least one droplet ( 23 ), directly or via a liquid separation process within the internal gap ( 6 ), and the internal gap ( 6 ) comprising at least one hydrophobic surface ( 17 ), at least one processing zone ( 78 ) for processing samples ( 80 ) located in the processing zone ( 78 ), and a delivery zone ( 74 ) for delivering the at least one droplet ( 23 ) from the liquid input port ( 19 ′) to the at least one processing zone ( 78 ),
 wherein the delivery zone ( 74 ) is configured to provide a repeating pattern of interacting electrowetting force for simultaneously transporting the at least one droplet ( 23 ) within the delivery zone ( 74 ). 
 
     
     
         2 . The cartridge ( 2 ) according to  claim 1 , comprising at least two separate processing zones for simultaneously and/or identically processing samples located in the at least two processing zones. 
     
     
         3 . The cartridge ( 2 ) according to  claim 1 , wherein the droplet ( 23 ) is a microfluidic droplet and/or a liquid comprising at least one of: a reagent, a buffer, a diluent, an extraction liquid, a washing liquid and a suspension, which in particular is a suspension of magnetic beads, single cells or cell aggregates. 
     
     
         4 . The cartridge ( 2 ) according to  claim 1 , comprising a first part ( 4 ) with the liquid input port ( 19 ′) and a second part ( 3 ) attached to the first part ( 3 ), such that the gap ( 6 ) is formed between the first part and the second part. 
     
     
         5 . The cartridge ( 2 ) according to  claim 4 , wherein the first part ( 4 ) comprises a rigid body and/or the second part ( 3 ) comprises or is an electrode support element ( 3 ″) or a flexible film, in particular a polymer film and/or an electrically isolating film, and wherein in particular the second part is attached to a peripheral side structure of the first part. 
     
     
         6 . The cartridge ( 2 ) according to  claim 4 , wherein the gap ( 6 ) is defined by a spacer ( 5 ) that is arranged between the first part and the second part, wherein in particular the spacer ( 5 ) comprises the liquid input port ( 19 ′), and/or by the shape of at least one of the two parts of the cartridge ( 2 ), in particular by a flexible part or a rigid part of the cartridge ( 2 ). 
     
     
         7 . The cartridge ( 2 ) according to  claim 1 , wherein the delivery zone ( 74 ) comprises a plurality of electrodes ( 10 ), in particular an electrode array ( 9 ), for applying an electrowetting force to the droplets ( 23 ). 
     
     
         8 . The cartridge ( 2 ) according to  claim 1 , wherein the delivery zone ( 74 ) comprises substantially identical and spaced apart electrodes ( 10 ) that are electrically connected to a common electrical interface ( 90 ) of the cartridge ( 2 ). 
     
     
         9 . The cartridge ( 2 ) according to  claim 1 ,
 wherein the repeated pattern comprises at least four electrodes in longitudinal direction, at least two of them being operated differently.   
     
     
         10 . The cartridge ( 2 ) according to  claim 1 , configured to manipulate droplets located in the processing zones ( 78 ) independently and/or asynchronously from droplets located in the delivery zone ( 74 ). 
     
     
         11 . The cartridge according to  claim 1 , comprising at least one waste removal zone ( 84 ) configured to provide a repeated pattern of electrowetting force for simultaneously transporting the at least one droplet within the waste removal zone ( 84 ). 
     
     
         12 . The cartridge ( 2 ) according to  claim 1 , wherein the waste removal zone ( 84 ) is arranged adjacent to the processing zone ( 78 ) and opposite to the delivery zone ( 74 ), further comprising at least one optical reading zone adjacent to the processing zone ( 78 ). 
     
     
         13 . The cartridge ( 2 ) according to  claim 1 , comprising a waste removal line with an output port, which in particular is arranged adjacent to the liquid input port. 
     
     
         14 . An electrowetting sample processing system ( 1 ), in particular a biological sample processing system, comprising a cartridge ( 2 ) according to  claim 1 . 
     
     
         15 . An electrowetting sample processing system ( 1 ), in particular a biological sample processing system, comprising a liquid input port ( 19 ′) for introducing an input liquid into an internal gap ( 6 ) of the electrowetting sample processing system, the input liquid providing for at least one droplet ( 23 ), directly or via a liquid separation process within the internal gap ( 6 ), and the internal gap ( 6 ) comprising at least one hydrophobic surface ( 17 ), at least one processing zone ( 78 ) for processing samples located in the processing zone ( 78 ), and a delivery zone ( 74 ) for delivering the at least one droplet ( 23 ) from the liquid input port ( 19 ′) to the at least one processing zone ( 78 ),
 wherein the delivery zone ( 74 ) is configured to provide a repeating pattern of interacting electrowetting force for simultaneously transporting the at least one droplet ( 23 ) within the delivery zone ( 74 ). 
 
     
     
         16 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising at least two separate processing zones ( 78 ) for simultaneously and/or identically processing samples located in the at least two processing zones ( 78 ). 
     
     
         17 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising a spacer ( 5 ) that defines the height of the internal gap ( 6 ). 
     
     
         18 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising a plurality of electrodes ( 10 ) for applying an electrowetting force to the droplets ( 23 ), in particular an electrode array ( 9 , 10 ), further in particular a two-dimensional electrode array. 
     
     
         19 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising periodically interconnected electrodes for simultaneously transporting droplets in the delivery zone ( 74 ). 
     
     
         20 . The electrowetting sample processing system ( 1 ) according to  claim 14 , wherein the electrodes are substantially identical and/or connected to a common electrical interface ( 90 , 14 ′), in particular to an electrical connector ( 14 ′) and/or contact field. 
     
     
         21 . The electrowetting sample processing system ( 1 ) according to  claim 19 , wherein the electrodes are arranged in at least two different groups, each group comprising electrically interconnected electrodes that are operated according to a predetermined offset in time. 
     
     
         22 . The electrowetting sample processing system ( 1 ) according to  claim 14 , wherein the electrodes are configured to manipulate the droplets located in the processing zones ( 78 ) independently and/or asynchronously from droplets located in the delivery zone ( 74 ). 
     
     
         23 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising a controller ( 14 ) for providing electrical control signals to the electrodes, in particular via an electrical interface of the cartridge. 
     
     
         24 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising electrodes for operating at least one waste removal zone ( 84 ), which is arranged at a side of the processing zone ( 78 ) that is located opposite to the delivery zone ( 74 ). 
     
     
         25 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising a two-dimensional array with processing zones ( 78 ) arranged in parallel, in particular an array with at least 4 zones, further in particular with at least 8 zones. 
     
     
         26 . The electrowetting sample processing system ( 1 ) according to  claim 14 , comprising a liquid input feed, in particular a droplet generator or a continuous feed, that is configured to operate independently and/or asynchronously from the operation of electrodes used for electrowetting. 
     
     
         27 . A method for operating the cartridge ( 2 ) or the electrowetting sample processing system ( 1 ) according to  claim 14 . 
     
     
         28 . A method for operating a cartridge ( 2 ) or an electrowetting sample processing system ( 1 ) that comprises an internal gap ( 6 ) with at least one processing zone ( 78 ) and at least one delivery zone ( 74 ), the method comprising:
 providing an input liquid into an internal gap ( 6 ) of the cartridge ( 2 ) for providing at least one droplet ( 23 ), directly or via a liquid separation process within the cartridge ( 2 );   transferring the at least one droplet ( 23 ) to the at least one processing zone ( 78 ) via the delivery zone ( 74 ) by repeating pattern of interacting electrowetting force to the at least one droplet ( 23 ) during its movement in the delivery zone.   
     
     
         29 . The method according to  claim 27 , wherein the electrowetting force is provided by a plurality of electrodes, in particular by an electrode array ( 9 ; 10 ), further in particular by a two-dimensional electrode array. 
     
     
         30 . The method according to  claim 27 , comprising the process of manipulating the at least one droplet ( 23 ) located in the delivery zone ( 74 ) independently and/or asynchronously from a droplet ( 23 ) located in the at least one processing zone ( 78 ). 
     
     
         31 . The method according to  claim 27 , comprising delivering of the at least one droplet ( 23 ) to a staging position ( 88 ) prior to a need in the at least one processing zone ( 78 ) and/or moving the at least one droplet ( 23 ) into the at least one processing zone ( 78 ) when required for processing.