Flow cells utilizing surface-attached structures, and related systems and methods

Abstract

A flow cell is provided that includes surface-attached structures in a chamber. The structures are movable in response to a magnetic or electric field. A target extraction or isolation system includes the flow cell and a driver configured for applying a magnetic or electric field to the interior of the flow cell to actuate movement of the structures. The flow cell may be utilized to extract or isolate a target from a sample flowing through the flow cell. Further, a microfluidic system is provided that includes surface-attached structures and a microarray, wherein actuated motion of the surface-attached structures is used to enhance flow, circulation, and/or mixing action for analyte capture on the microarray.

1 - 83 . (canceled) 
     
     
         84 . A target extraction system, comprising:
 a flow cell with a plurality of flow cell units, such that the fluid inlet or the fluid outlet of each flow cell unit communicates with the fluid inlet or the fluid outlet of at least one other flow cell unit. each flow cell unit comprising a chamber and a plurality of surface-attached structures to the inside surface at a plurality of respective attachment sites and extending into the interior therefrom, and a driver configured for applying a magnetic or electric field to the interior of the flow cell to actuate movement of the surface-attached structures; wherein application of a magnetic or electric field actuates the surface-attached structure into movement relative to the corresponding attachment site.   
     
     
         85 . A target extraction system of  claim 84 , wherein the driver is configured for varying a parameter of the magnetic or electric field selected from the group consisting of:
 magnetic or electric field strength; magnetic or electric field direction; a frequency at which the magnetic or electric field is cycled between ON and OFF states or high-strength and low-strength states; and a combination of two or more of the foregoing.   
     
     
         86 . The target extraction system of  claim 84 , wherein the driver comprises electromagnets or electrodes, and the driver is configured for varying electrical power applied to the electromagnets or the electrodes. 
     
     
         87 . The target extraction system of  claim 84 , wherein the driver comprises one or more magnets, and the driver is configured for moving one or more of the magnets relative to the housing; for moving one or more of the magnets in a reciprocating manner. 
     
     
         88 . The target extraction system of  claim 84 , wherein the driver is configured for rotating one or more of the magnets about a longitudinal axis of the flow cell, or for moving one or more of the magnets in a direction toward or away from the flow cell, or both of the foregoing. 
     
     
         89 . The target extraction system of any of  claim 84 , wherein the driver comprises a motor configured for powering movement of one or more of the magnets. 
     
     
         90 . The target extraction system of any of  claim 84 , comprising a fluid supply source configured for flowing a fluid to a fluid input of the flow cell, the fluid supply source comprising a sample source configured for flowing a target-containing sample to the fluid input; wherein the sample source is configured for flowing the target-containing sample to the fluid inputs of the flow cell units simultaneously when the plurality of flow cell units are arranged in parallel; or the sample source is configured for flowing the target-containing sample to the fluid input of a first flow cell unit of the plurality of flow cell units arranged in series. 
     
     
         91 . The target extraction system of  claim 84 , comprising a processing fluid source configured for flowing a processing fluid to the fluid input of the flow cell, wherein the processing fluid source is selected from the group consisting of: a source of processing fluid comprising a release agent effective for releasing targets bound to a surface inside the flow cell; a source of processing fluid comprising a rinsing agent effective for purging the flow cell of residual components from a previous operation of the flow cell; and both of the foregoing; wherein the processing fluid source comprises a source of release agent selected from the group consisting of: a chemical lysing agent; a pH cell lysing agent; an enzymatic liquefaction agent; and a solvent. 
     
     
         92 . The target extraction system of any of  claim 84 , further comprising a photon source configured for directing photons into the flow cell under conditions effective for releasing targets bound to the surface-attached structures by photolysis. 
     
     
         93 . The target extraction system of any of  claim 84 , comprising a receptacle configured for receiving processed fluid from the fluid output of the flow cell units simultaneously, when the plurality of flow cell units are arranged in parallel; and the receptacle configured for receiving processed fluid from the fluid output of a last flow cell unit when the plurality of flow cell units are arranged in series; wherein the receptacle is part of or communicates with an analytical instrument configured for measuring an attribute of the targets collected from the flow cell units. 
     
     
         94 . A method for extracting a target from a sample, the method comprising:
 flowing a target-containing sample through a flow cell and into contact with surface-attached structures disposed in the flow cell, wherein the surface-attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, and the surface-attached structures are movable in the flow cell relative to the attachment sites in response to magnetic or electric actuation; and   while flowing the sample, isolating targets of the sample from a remaining portion of the sample.   
     
     
         95 . The method of  claim 94 , wherein isolating targets comprises binding the targets to a binding agent disposed in the flow cell; wherein the binding agent is selected from the group consisting of: a binding agent disposed on or integrated with an outer surface of at least some of the surface-attached structures;
 a binding agent disposed on or integrated with the inside surface; and   both of the foregoing.   
     
     
         96 . The method of  claim 94 , wherein isolating targets comprises releasing the targets after binding, such that the released targets are flowable out from the flow cell; wherein releasing selected from the group consisting of:
 flowing a release agent through the flow cell and into contact with the bound targets;   irradiating the bound targets with photons under conditions effective for inducing photolysis;   applying a shear force to the bound targets at a magnitude effective for unbinding the bound targets; and   a combination of two or more of the foregoing.   
     
     
         97 . The method of  claim 94 , wherein isolating targets comprises, releasing the targets after binding, such that the released targets are flowable out from the flow cell; wherein releasing comprises flowing a release agent through the flow cell and into contact with the bound targets, and the release agent is selected from the group consisting of: a chemical lysing agent; a pH cell lysing agent; an enzymatic liquefaction agent; and a solvent. 
     
     
         98 . The method of  claim 94 , wherein isolating targets comprises, releasing the targets after binding, such that the released targets are flowable out from the flow cell; wherein releasing comprises applying a shear force to the bound targets at a magnitude effective for unbinding the bound targets, and applying the shear force is selected from the group consisting of:
 flowing a liquid through the flow cell at a flow rate effective for releasing the bound targets by shearing;   applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures at a speed effective for releasing the bound targets by shearing;   both of the foregoing.   
     
     
         99 . The method of  claim 94 , wherein a binding agent is disposed on or integrated with an outer surface of at least some of the surface-attached structures, and further comprising, while flowing the sample, applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures in a reciprocating manner to increase a time-averaged cross-section of the surface-attached structures. 
     
     
         100 . The method of  claim 94 , wherein isolating targets comprises trapping the targets by preventing the targets from passing between neighbouring surface-attached structures; and after trapping, releasing the targets by applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures. 
     
     
         101 . The method of  claim 94 , wherein isolating targets comprises separating the targets from non-targets of the sample by size or density, such that the targets and the non-targets elute from the flow cell at different times; wherein: the targets have a different size than the non-targets; the inside surface is a top inside surface, and the flow cell further comprises a bottom inside surface spaced from the top inside surface such that a structure-free region is between the surface-attached structures and the bottom inside surface; and the surface-attached structures are positioned with an inter-structure spacing effective for forcing either the targets or the non-targets, whichever are larger, to flow substantially only through the structure-free region; and wherein:
 the targets have a different density than the non-targets; the inside surface is a top inside surface, and the flow cell further comprises a bottom inside surface spaced from the top inside surface such that a structure-free region is between the surface-attached structures and the bottom inside surface and is below the surface-attached structures; and flowing the sample through the flow cell is done at a flow rate effective for allowing a majority of either the targets or the non-targets, whichever are denser, to diffuse into the structure-free region and toward the bottom inside surface.   
     
     
         102 . The method of  claim 94 , comprising, while flowing the sample, applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures; comprising moving the surface-attached structures at a speed or frequency effective for causing an effect selected from the group consisting of:
 adjusting or varying an inter-structure spacing between the surface-attached structures;   preventing or disrupting clogging of sample material between the surface-attached structures;   preventing or disrupting non-specific binding of sample material on the surface-attached structures; and   a combination of two or more of the foregoing.   
     
     
         103 . The method of any of  claim 94 , comprising, after isolating the targets, transferring the targets to an analytical instrument, and operating the analytical instrument to measure an attribute of the targets. 
     
     
         104 . A method for extracting a target from a sample, the method comprising:
 flowing a target-containing sample through a flow cell and into contact with surface-attached structures disposed in the flow cell, wherein the surface-attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, and the surface-attached structures are movable in the interior relative to the attachment sites in response to magnetic or electric actuation; and   while flowing the sample, capturing the targets on the surface-attached structures, or on the inside surface, or on both the surface-attached structures and the inside surface, and wherein capturing produces a depleted sample containing a reduced concentration of the targets.   
     
     
         105 . The method of  claim 104 , comprising outputting the depleted sample from the flow cell, wherein the captured targets remain captured in the flow cell, and releasing the captured targets and outputting the released targets from the flow cell. 
     
     
         106 . A method for extracting a target from a sample, the method comprising:
 flowing a target-containing sample through a flow cell and into contact with surface-attached structures disposed in the flow cell, wherein the surface-attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, and the surface-attached structures are movable in the flow cell relative to the attachment sites in response to magnetic or electric actuation; and while flowing the sample, isolating targets of the sample from a remaining portion of the sample; wherein, applying the magnetic or electric field moves the surface-attached structures at a speed or frequency effective for causing an effect selected from the group consisting of:   releasing the targets bound to the surface-attached structures by shearing; adjusting or varying an inter-structure spacing between the surface-attached structures;   preventing or disrupting clogging of sample material between the surface-attached structures;   preventing or disrupting non-specific binding of sample material on the surface-attached structures; and   a combination of two or more of the foregoing.   
     
     
         107 . The method for extracting a target from a sample of  claim 94 , wherein the target is a non-analyte target comprising an interferent, suppressant, and/or element contributing only to background signal, and wherein the non-analyte target is isolated from the sample to purge the sample of the non-analyte target and/or to analyze the sample in the absence of the non-analyte target. 
     
     
         108 . A flow cell or system configured for performing the method of extracting a target from a sample, comprising a plurality of binding agents, wherein at least some of the binding agents are disposed on or integrated with outer surfaces of at least some of the surface-attached structures; wherein the binding agents disposed on or integrated with the outer surfaces are arranged in a plurality of groups, and the groups are spaced from each other as a one-dimensional or two-dimensional array of groups, and wherein each group is separated by one or more adjacent groups by surface-attached structures that do not include binding agents; wherein the groups are spaced from each other as a two-dimensional array of groups comprising a plurality of rows of groups, and each row is staggered or offset relative to a row adjacent thereto 
     
     
         109 . The flow cell of  claim 108 , comprising a plurality of binding agents, wherein at least some of the binding agents are arranged as a microarray spaced from the plurality of surface-attached structures by a gap in the interior; wherein the microarray is arranged as a plurality of capture sites, each capture site comprising one or more of the binding agents;
 wherein the microarray is arranged as a two-dimensional array of capture sites comprising a plurality of rows of capture sites, and each row is staggered or offset relative to a row adjacent thereto   
     
     
         110 . The flow cell of  claim 109 , wherein the microarray is selected from the group consisting of a DNA microarray, an MMChip, a protein microarray, a peptide microarray, a tissue microarray, a cellular microarray, a small molecule microarray, a chemical compound microarray, an antibody microarray, a carbohydrate microarray, a phenotype microarray, and a reverse phase protein microarray. 
     
     
         111 . The flow cell of  claim 109 , comprising a detector in operative communication with the microarray, wherein the microarray comprises a substrate configured for transmitting photons, at an angle from about 0 degrees to about 45 degrees; and the detector comprises a florescence-based optical detection mechanism; wherein the microarray comprises an electrically conductive or semiconductor substrate, and the detector comprises an electrical signal-based detection mechanism. 
     
     
         112 . The flow cell of  claim 109 , comprising a detector configured for measuring a property of a fluid in the interior, a property of the surface-attached structures, or a property of binding agents in the interior. 
     
     
         113 . The flow cell of  claim 109 , wherein the surface-attached structures are oriented substantially along a direction normal to the inside surface at which are the surface-attached structures attached, or are oriented at an angle with respect to the direction normal to the inside surface. 
     
     
         114 . The flow cell of  claim 109 , wherein the surface-attached structures have a configuration selected from the group consisting of:
 the surface-attached structures are configured to move with a side-to-side two-dimensional motion;   the surface-attached structures are configured to move with a circular motion;   the surface-attached structures are configured to move in a tilted motion relative to the inside surface to which the surface-attached structures are attached;   a combination or two or more of the foregoing.   
     
     
         115 . A microfluidic device, comprising:
 a chamber enclosing an interior configured for containing a fluid, the chamber comprising an inside surface facing the interior; and   a plurality of surface-attached structures attached to the inside surface at a plurality of respective attachment sites and extending into the interior therefrom, each surface-attached structure being movable in response to an actuation force selected from the group consisting of: a magnetic force, a thermal force, a sonic force, an optical force, an electrical force, and a vibrational force.   
     
     
         116 . The microfluidic device of  claim 115 , comprising a fluid port communicating with the chamber, wherein the fluid port is sealable or closable, a fluid inlet and a fluid outlet separate from the fluid inlet, the fluid inlet and the fluid outlet communicating with the chamber, and a plurality of analyte capture elements disposed in the interior; wherein the analyte capture elements are disposed on the inside surface, on a substrate separate from the inside surface, on one or more of the surface-attached structures, or a combination of two or more of the foregoing. 
     
     
         117 . A method of reducing reaction time of an assay comprising conducting the assay in the microfluidic device of  claim 115  wherein the reaction time is reduced by at least about six times (6×) as compared to microfluidic devices that do not utilize the motion of surface-attached structures due to actuation forces to enhance the flow, circulation, and/or mixing action of a fluid sample. 
     
     
         118 . A method of enhancing flow, circulation, and/or mixing action of a fluid sample comprising: depositing the fluid sample in the chamber of the microfluidic device of  claim 115 ; and applying the actuation force to the surface-attached structures;
 wherein the flow, circulation, and/or mixing action of the fluid sample is enhanced as compared to microfluidic devices that do not utilize the motion of surface-attached structures due to actuation forces.