Patent Publication Number: US-2021187505-A1

Title: Fluid processing and control

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     1011 This application is a continuation of U.S. application Ser. No. 16/704,733, filed Dec. 5, 2019, which is a continuation of U.S. application Ser. No. 15/601,725, filed May 22, 2017, now U.S. Pat. No. 10,525,468, which is a continuation of U.S. patent application Ser. No. 14/169,402, filed Jan. 31, 2014, now U.S. Pat. No. 9,669,409, which is a continuation of U.S. patent application Ser. No. 13/854,297, filed Apr. 1, 2013, now U.S. Pat. No. 8,673,238, which is a divisional of U.S. patent application Ser. No. 13/245,572, filed Sep. 26, 2011, now U.S. Pat. No. 8,431,413, which is a divisional of U.S. patent application Ser. No. 10/084,409, filed Feb. 25, 2002, now U.S. Pat. No. 8,048,386, and is related to commonly assigned U.S. patent application Ser. No. 09/648,570, filed Aug. 25, 2000, now U.S. Pat. No. 6,374,684, the entire disclosure of all of the above is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates generally to fluid manipulation and, more particularly, to a system and method for metering and distributing fluid for processing and analysis. 
     The analysis of fluids such as clinical or environmental fluids generally involves a series of processing steps, which may include chemical, optical, electrical, mechanical, thermal, or acoustical processing of the fluid samples. Whether incorporated into a bench-top instrument, a disposable cartridge, or a combination of the two, such processing typically involves complex fluidic assemblies and processing algorithms. 
     Conventional systems for processing fluid samples employ a series of chambers each configured for subjecting the fluid sample to a specific processing step. As the fluid sample flows through the system sequentially from chamber to chamber, the fluid sample undergoes the processing steps according to a specific protocol. Because different protocols require different configurations, conventional systems employing such sequential processing arrangements are not versatile or easily adaptable to different protocols. 
     SUMMARY OF THE INVENTION 
     The present invention provides an apparatus and method for manipulating fluids, for instance, to determine the presence or absence of an analyte in a sample. In a specific embodiment, the apparatus employs a rotary valve configuration that allows fluidic communication between a fluid processing region selectively with a plurality of chambers including, for example, a sample chamber, a waste chamber, a wash chamber, a lysis chamber, and a mastermix or reagent chamber. The fluid flow among the fluid processing region and the chambers is controlled by adjusting the position of the rotary valve. In this way, the metering and distribution of fluids in the apparatus can be varied depending on the specific protocol. Unlike conventional devices, the fluid flow is no longer limited to a specific protocol. 
     In accordance with an aspect of the present invention, a fluid control and processing system comprises a housing having a plurality of chambers, and a valve body including a first fluid processing region continuously coupled fluidicly with a fluid displacement region. The fluid displacement region is depressurizable to draw fluid into the fluid displacement region and pressurizable to expel fluid from the fluid displacement region. The valve body includes a plurality of external ports. The first fluid processing region is fluidicly coupled with at least two of the external ports. The fluid displacement region is fluidicly coupled with at least one of the external ports of the valve body. The valve body is adjustable with respect to the housing to allow the external ports to be placed selectively in fluidic communication with the plurality of chambers. At least one of the plurality of chambers is a processing chamber including a first port and a second port for selectively communicating with at least one of the external ports of the valve body. The processing chamber provides an additional fluid processing region. 
     In some embodiments, at least one of the fluid processing regions in the valve body or in the processing chamber contains a fluid processing material which is an enrichment material or a depletion material. The fluid processing material may comprise at least one solid phase material. The solid phase material may comprise at least one of beads, fibers, membranes, filter paper, glass wool, polymers, and gels. The fluid processing material may comprise a filter and beads, or at least two types of beads. In a specific embodiments, a single type of beads is used to perform at least two different functions which are selected from the group consisting of cell capture, cell lysis, binding of analyte, and binding of unwanted material. In some embodiments, the processing chamber includes a receiving area for receiving a processing module containing an enrichment material or a depletion material. In a specific embodiment, at least one of the chambers is a reagent chamber containing dried or lyophilized reagents. 
     In some embodiments, the fluid processing material comprises at least one liquid phase material, such as ficoll, dextran, polyethylene glycol, and sucrose. The fluid processing material is contained in the fluid processing region by one or more frits. In a specific embodiment, the external ports are disposed on a generally planar external port surface of the valve body. 
     In accordance with another aspect of the invention, a fluid control and processing system comprises a housing having a plurality of chambers and at least one separation channel (e.g., for performing capillary electrophoresis or isoelectric focusing), and a valve body including a fluid processing region continuously coupled fluidicly with a fluid displacement region. The fluid displacement region is depressurizable to draw fluid into the fluid displacement region and pressurizable to expel fluid from the fluid displacement region. The valve body includes at least one external port, the fluid processing region is fluidicly coupled with the at least one external port, and the fluid displacement region is fluidicly coupled with at least one external port of the valve body. The valve body is adjustable with respect to the housing to allow the at least one external port to be placed selectively in fluidic communication with the plurality of chambers and with the at least one separation channel. 
     In some embodiments, a plurality of electrodes are coupled to the housing to apply an electric field across at least a portion of the separation channel. The electrodes preferably comprise a pair of metal tubes at the two opposite ends of the separation channel. Reservoirs are provided at both ends of the separation channel, and a reservoir port is provided at one of the reservoirs for communicating with the at least one external port of the valve body. 
     Another aspect of the present invention is directed to a method for controlling fluid flow between a valve, a plurality of chambers, and at least one separation channel, wherein the valve includes at least one external port and a fluid displacement region continuously coupled fluidicly with a fluid processing region which is fluidicly coupled with the at least one external port. The method comprises adjusting the valve with respect to the plurality of chambers and the at least one separation channel to place the at least one external port selectively in fluidic communication with the plurality of chambers and the at least one separation channel. 
     In some embodiments, an electric field is applied across at least a portion of the separation channel. The method may comprise optically detecting species bands in the separation channel. 
     In accordance with another aspect of the invention, a fluid control and processing system comprises a housing having a plurality of chambers, and a valve body including a fluid processing region continuously coupled fluidicly with a fluid displacement region. The fluid displacement region is depressurizable to draw fluid into the fluid displacement region and pressurizable to expel fluid from the fluid displacement region. The valve body includes an external port. The fluid processing region is fluidicly coupled with the external port. The fluid displacement region is fluidicly coupled with the external port of the valve body. The valve body is adjustable with respect to the housing to allow the external port to be placed selectively in fluidic communication with the plurality of chambers. 
     In some embodiments, the valve body is adjustable with respect to the housing to close the external port so that the fluid displacement region and the fluid processing region are fluidicly isolated from the chambers. At least one of the chambers and the fluid processing region may contain an enrichment material or a depletion material. The fluid displacement region is depressurizable by increasing in volume and is pressurizable by decreasing in volume. A fluid displacement member is disposed in the fluid displacement region, and is movable to adjust the volume of the fluid displacement region. An energy transmitting member is operatively coupled with the fluid processing region for transmitting energy thereto to process fluid contained therein. 
     In specific embodiments, the valve body includes a crossover channel. The valve body is adjustable with respect to the housing to place the crossover channel in fluidic communication with an aspiration chamber and a source chamber to permit aspiration of a fluid from the source chamber through the crossover channel to the aspiration chamber. The body is rotatably adjustable around an axis. The at least one external port is disposed within a range of external port radii from the axis and the crossover channel is disposed within a range of crossover channel radii from the axis. The range of external port radii and the range of crossover channel radii are non-overlapping. The crossover channel may be a circular arc lying on a common crossover channel radius from the axis. 
     In accordance with another aspect of the present invention, a fluid control and processing system for controlling fluid flow among a plurality of chambers comprises a body including a fluid processing region continuously coupled fluidicly with a fluid displacement region. The fluid displacement region is depressurizable to draw fluid into the fluid displacement region and pressurizable to expel fluid from the fluid displacement region, the body including at least one external port. The fluid processing region is fluidicly coupled with the at least one external port. The fluid displacement region is fluidicly coupled with at least one external port of the valve body. The body is rotatably adjustable and relative to the plurality of chambers to place the at least one external port selectively in fluidic communication with the plurality of chambers. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of the fluid control and processing system according to an embodiment of the present invention; 
         FIG. 2  is another perspective view of the system of  FIG. 1 ; 
         FIG. 3  is an exploded view of the system of  FIG. 1 ; 
         FIG. 4  is an exploded view of the system of  FIG. 2 ; 
         FIG. 5  is an elevational view of a fluid control apparatus and gasket in the system of  FIG. 1 ; 
         FIG. 6  is a bottom plan view of the fluid control apparatus and gasket of  FIG. 5 ; 
         FIG. 7  is a top plan view of the fluid control apparatus and gasket of  FIG. 5 ; 
         FIG. 8  is a cross-sectional view of the rotary fluid control apparatus of  FIG. 7  along  8 - 8 ; 
         FIGS. 9A-9LL  are top plan views and cross-sectional views illustrating a specific protocol for controlling and processing fluid using the fluid control and processing system of  FIG. 1 ; 
         FIG. 10  is an exploded perspective view of the fluid control and processing system according to another embodiment of the present invention; 
         FIG. 11  is a cross-sectional view of a fluid control apparatus in the system of  FIG. 10 ; 
         FIGS. 12A-12N  are plan views illustrating a specific protocol for controlling and processing fluid using the fluid control and processing system of  FIG. 10 ; 
         FIG. 13  is a cross-sectional view of a soft-walled chamber; 
         FIG. 14  is a cross-sectional view of a piston assembly; 
         FIG. 15  is a cross-sectional view of a side filtering chamber; 
         FIG. 16  is a top plan view of a fluid control and processing system including a processing chamber according to another embodiment of the present invention; 
         FIG. 17  is a perspective view of the processing chamber of  FIG. 16 ; 
         FIG. 18  is a partially cut-out, sectional view of the fluid control and processing system of  FIG. 16 ; 
         FIG. 19  is a sectional perspective view of the processing chamber of  FIG. 16   
         FIG. 20  is a perspective view of a retaining member of the processing chamber of  FIG. 16 ; 
         FIG. 21  is an elevational view of the retaining member of  FIG. 20 ; 
         FIG. 22  is a top plan view of the retaining member of  FIG. 20 ; 
         FIG. 23  is a cross-sectional view of the retaining member along  23 - 23  of  FIG. 22 ; 
         FIG. 24  is a sectional view of a fluid control and processing system including a separation channel according to another embodiment of the present invention; 
         FIG. 25  is a cross-sectional view of a fluid control apparatus in a fluid control and processing system according to another embodiment of the present invention; and 
         FIGS. 26A-26EE  are top plan views and cross-sectional views illustrating a specific protocol for controlling and processing fluid using the fluid control and processing system of  FIG. 25 . 
     
    
    
     DESCRIPTION OF THE SPECIFIC EMBODIMENTS 
       FIGS. 1-4  show a fluid control and processing system  10  including a housing  12  having a plurality of chambers  13 .  FIG. 1  shows the chambers  13  exposed for illustrative purposes. A top cover will typically be provided to enclose the chambers  13 . As best seen in  FIGS. 3 and 4 , a fluid control device  16  and a reaction vessel  18  are connected to different portions of the housing  12 . The fluid control device in the embodiment shown is a rotary fluid control valve  16 . The valve  16  includes a valve body  20  having a disk portion  22  and a tubular portion  24 . The disk portion  22  has a generally planar external port surface  23 , as best seen in  FIG. 3 . The valve  16  is rotatable relative to the housing  12 . The housing  12  includes a plurality of chamber ports  25  facing the external port surface  23  of the disk portion  22  of the valve  16  ( FIG. 4 ) to permit fluidic communication between the chambers  13  and the valve  16 . An optional seal or gasket  26  is disposed between the disk portion  22  and the housing  12 . The disk portion  22  further includes a filter or a filter stack  27  and an outer cover  28 , and a toothed periphery  29 . The cover  28  may be a rigid shell or a flexible film. 
     As best seen in  FIG. 4 , the disk portion  22  includes a fluid processing region  30 . As used herein, the term “fluid processing region” refers to a region in which a fluid is subject to processing including, without limitation, chemical, optical, electrical, mechanical, thermal, or acoustical processing. For example, chemical processing may include a catalyst; optical processing may include U.V. activation; electrical processing may include electroporation or electrophoresis or isoelectric focusing; mechanical processing may include mixing, filtering, pressurization, and cell disruption; thermal processing may include heating or cooling; and acoustical processing may include the use of ultrasound. The fluid processing region may include an active member, such as the filter  27 , to facilitate processing of the fluid. Examples of active members include a microfluidic chip, a solid phase material, a filter or a filter stack, an affinity matrix, a magnetic separation matrix, a size exclusion column, a capillary tube, or the like. Suitable solid phase materials include, without limitation, beads, fibers, membranes, filter paper, lysis paper impregnated with a lysing agent, glass wool, polymers, or gels. In a specific embodiment, the fluid processing region is used to prepare a sample for further processing, for instance, in the reaction vessel  18 . 
     As shown in  FIGS. 5-8 , the outer cover  28  encloses the fluid processing region  30  and the bottom end of the disk portion  22  of the valve  16 . In  FIG. 8 , the processing region  30  includes a first fluid processing port  32  coupled to a first fluid processing channel  34 , and a second fluid processing port  36  coupled to a second fluid processing channel  38 . The first fluid processing channel  34  is coupled to a first outer conduit  40  ending at a first external port  42  at the external port surface  23 , while the second fluid processing channel  38  is coupled to a second outer conduit  44  ending at a second external port  46  at the external port surface  23 . A fluid displacement channel  48  is coupled to the first fluid processing channel  34  and first conduit  40  near one end, and to a fluid displacement region  50  at the other end. The first outer conduit  40  serves as a common conduit for allowing fluidic communication between the first external port  42  and either or both of the first fluid processing channel  34  and the fluid displacement channel  48 . The processing region  30  is in continuous fluidic communication with the fluid displacement region  50 . 
     As shown in  FIGS. 6-8 , the external ports  42 ,  46  are angularly spaced from one another relative to the axis  52  of the valve  16  by about 180°. The external ports  42 ,  46  are spaced radially by the same distance from the axis  52 . The axis  52  is perpendicular to the external port surface  23 . In another embodiment, the angular spacing between the external ports  42 ,  46  may be different. The configuration of the channels in the disk portion  22  may also be different in another embodiment. For example, the first fluid processing channel  34  and the first outer conduit  40  may be slanted and coupled directly with the fluid displacement region  50 , thereby eliminating the fluid displacement channel  48 . The second fluid displacement channel  38  may also be slanted and extend between the second fluid processing port  36  and the second external port  46  via a straight line, thereby eliminating the second outer conduit  44 . In addition, more channels and external ports may be provided in the valve  16 . As best seen in  FIG. 3 , a crossover channel or groove  56  is desirably provided on the external port surface  23 . The groove  56  is curved and desirably is spaced from the axis  52  by a constant radius. In one embodiment, the groove  56  is a circular arc lying on a common radius from the axis  52 . As discussed in more detail below, the groove  56  is used for filling the vessel. 
     As shown in  FIG. 8 , the fluid displacement region  50  is disposed substantially within the tubular portion  24  of the valve  16  and extends partially into the disk portion  22 . In a preferred embodiment, the fluid displacement region  50  is a pumping channel or chamber. A fluid displacement member in the form of a plunger or piston  54  is movably disposed in the pumping chamber  50 . When the piston  54  moves upward, it expands the volume of the pumping chamber  50  to produce a suction for drawing fluid into the pumping chamber  50 . When the piston  54  moves downward, it decreases the volume of the pumping chamber  50  to drive fluid out of the chamber  50 . Alternatively, for example, pressurization and depressurization of the displacement region  50  may be carried out using a diaphragm, an external pneumatic or pressure control system, or the like. 
     As the rotary valve  16  is rotated around its axis  52  relative to the housing  12  of  FIGS. 1-4 , one of the external ports  42 ,  46  may be open and fluidicly coupled with one of the chambers  13  or reaction vessel  18 , or both external ports  42 ,  46  may be blocked or closed. In this embodiment, at most only one of the external ports  42 ,  46  is fluidicly coupled with one of the chambers or reaction vessel  18 . Other embodiments may be configured to permit both external ports  42 ,  46  to be fluidicly coupled with separate chambers or the reaction vessel  18 . Thus, the valve  16  is rotatable with respect to the housing  12  to allow the external ports  42 ,  46  to be placed selectively in fluidic communication with a plurality of chambers which include the chambers  13  and the reaction vessel  18 . Depending on which external port  42 ,  46  is opened or closed and whether the piston  54  is moved upward or downward, the fluid flow in the valve  16  can change directions, the external ports  42 ,  46  can each switch from being an inlet port to an outlet port, and the fluid flow may pass through the processing region  30  or bypass the processing region  30 . In a specific embodiment, the first external port  42  is the inlet port so that the inlet side of the processing region  30  is closer to the fluid displacement region  50  than the outlet side of the processing region  30 . 
     To demonstrate the fluid metering and distribution function of the valve  16 ,  FIGS. 9A-9LL  illustrate the operation of the valve  16  for a specific protocol. In  FIGS. 9A and 9AA , the first external port  42  is placed in fluidic communication with a sample chamber  60  by rotating the valve  16 , and the piston  54  is pulled upward to draw a fluid sample from the sample chamber  60  through the first outer conduit  40  and fluid displacement channel  48  to the fluid displacement region  50 , bypassing the processing region  30 . For simplicity, the piston  54  is not shown in  FIGS. 9A-9LL . The valve  16  is then rotated to place the second external port  46  in fluidic communication with a waste chamber  64  as shown in  FIGS. 9B and 9BB . The piston  54  is pushed downward to drive the fluid sample through the fluid processing region  30  to the waste chamber  64 . In a specific embodiment, the fluid processing region  30  includes a filter or a filter stack  27  for capturing sample components (e.g., cells, spores, microorganisms, viruses, proteins, or the like) from the fluid sample as it passes therethrough. An example of a filter stack is described in commonly assigned, copending U.S. patent application Ser. No. 09/584,327, entitled “Apparatus and Method for Cell Disruption,” filed May 30, 2000, which is incorporated herein by reference in its entirety. In alternative embodiments, other active members may be provided in the processing region  30 . These first two steps of capturing sample components may be repeated as desired. 
     In  FIGS. 9C and 9CC , the valve  16  is rotated to place the first external port  42  in fluidic communication with a wash chamber  66 , and the piston  54  is pulled upward to draw a wash fluid from the wash chamber  66  into the fluid displacement region  50 , bypassing the processing region  30 . The valve  16  is then rotated to place the second external port  46  in fluidic communication with the waste chamber  64  as shown in  FIGS. 9D and 9DD . The piston  54  is pushed downward to drive the wash fluid through the fluid processing region  30  to the waste chamber  64 . The above washing steps may be repeated as desired. The intermediate washing is used to remove unwanted residue within the valve  16 . 
     In  FIGS. 9E and 9EE , the valve  16  is rotated to place the first external port  42  in fluidic communication with a lysis chamber  70 , and the piston  54  is pulled upward to draw a lysing fluid (e.g., a lysing reagent or buffer) from the lysis chamber  70  into the fluid displacement region  50 , bypassing the processing region  30 . The valve  16  is then rotated to place the second external port  46  in fluidic communication with the waste chamber  64  as shown in  FIGS. 9F and 9FF . The piston  54  is pushed downward to drive the lysing fluid through the fluid processing region  30  to the waste chamber  64 . In  FIGS. 9G, and 9GG , the valve  16  is rotated to close the external ports  42 ,  46 . The piston  54  is pushed downward to pressurize the remaining lysing fluid and the sample components captured in the fluid processing region  30 . Additional energy may be applied to the mixture in the processing region  30 . For instance, a sonic member  76  such as an ultrasonic horn may be placed in contact with the outer cover  28  to transmit sonic energy into the processing region  30  to facilitate lysing of the sample components. In one embodiment, the outer cover  28  is made of a flexible film which is stretched under pressure to contact the sonic member  76  during lysing to allow transmission of the sonic energy into the processing region  30 . 
     The cover  28  in one embodiment is a flexible film of polymeric material such as polypropylene, polyethylene, polyester, or other polymers. The film may either be layered, e.g., laminates, or the films may be homogeneous. Layered films are preferred because they generally have better strength and structural integrity than homogeneous films. In particular, layered polypropylene films are presently preferred because polypropylene is not inhibitory to polymerase chain reaction (PCR). Alternatively, the cover  28  may comprise other materials such as a rigid piece of plastic. In one preferred embodiment, the cover  28  is an interface wall which is dome-shaped or includes stiffening ribs as shown, for example, in PCT Publication WO 00/73413 entitled “Apparatus and Method for Cell Disruption,” or commonly assigned, copending U.S. patent application Ser. No. 09/972,221, entitled “Apparatus and Method for Rapid Disruption of Cells or Viruses,” filed Oct. 4, 2001, the entire disclosures of which are incorporated herein by reference. 
     In general, the energy transmitting member that is operatively coupled to the processing region  30  for transmitting energy thereto may be an ultrasonic, piezoelectric, magnetostrictive, or electrostatic transducer. The energy transmitting member may also be an electromagnetic device having a wound coil, such as a voice coil motor or a solenoid device. It is presently preferred that the energy transmitting member be a sonic member, such as an ultrasonic horn. Suitable horns are commercially available from Sonics &amp; Materials, Inc. having an office at 53 Church Hill, Newton, Conn. 06470-1614, U.S.A. Alternatively, the sonic member may comprise a piezoelectric disk or any other type of ultrasonic transducer that may be coupled to the cover  28 . In alternative embodiments, the energy transmitting member may be a thermal element (e.g., a heater) for transmitting thermal energy to the processing region  30  or an electrical element for transmitting electrical energy to the processing region  30 . In addition, multiple energy transmitting members may be employed simultaneously, e.g., simultaneously heating and sonicating the processing region to effect lysis of cells, spores, viruses, or microorganisms trapped in the processing region. 
     In  FIGS. 9H and 9HH , the valve  16  is rotated to place the second external port  46  in fluidic communication with a mastermix or reagent chamber  78 , and the piston  54  is pushed downward to elute the mixture from the processing region  30  to the reagent chamber  78 . The reagent chamber  78  typically contains reagents (e.g., nucleic acid amplification reagents and probes) to be mixed with the sample. Any excess mixture is dispensed into the waste chamber  64  via the second external port  46  after rotating the valve  16  to place the port  46  in fluidic communication with the waste chamber  64 , as shown in  FIGS. 9I and 9II . The mixture is then mixed in the reagent chamber  78  by toggling. This is carried out by placing the fluid displacement region  50  in fluidic communication with the reagent chamber  78  as shown in  FIGS. 9J and 9JJ , and moving the piston  54  up and down. Toggling of the mixture through the filter in the processing region  30 , for instance, allows larger particles trapped in the filter to temporarily move out of the way to permit smaller particles to pass through. The reagent chamber  78  may contain dried or lyophilized reagents that are reconstituted when mixed with fluid. 
     In  FIGS. 9K, 9KK, and 9K ′K′, the valve  16  is rotated to place the first external port  42  in fluidic communication with a first branch  84  coupled to the reaction vessel  18 , while the second branch  86  which is coupled to the reaction vessel  18  is placed in fluidic communication with the crossover groove  56 . The first branch  84  and second branch  86  are disposed at different radii from the axis  52  of the valve  16 , with the first branch  84  having a common radius with the first external port  42  and the second branch  86  having a common radius with the crossover groove  56 . The crossover groove  56  is also in fluidic communication with the reagent chamber  78  ( FIG. 9K ), and serves to bridge the gap between the reagent chamber  78  and the second branch  86  to provide crossover flow therebetween. The external ports are disposed within a range of external port radii from the axis and the crossover groove is disposed within a range of crossover groove radii from the axis, where the range of external port radii and the range of crossover groove radii are non-overlapping. Placing the crossover groove  56  at a different radius from the radius of the external ports  42 ,  46  is advantageous because it avoids cross-contamination of the crossover groove  56  by contaminants that may be present in the area near the surfaces between the valve  16  and the housing  12  at the radius of the external ports  42 ,  46  as a result of rotational movement of the valve  16 . Thus, while other configurations of the crossover groove may be used including those that overlap with the radius of the external ports  42 ,  46 , the embodiment as shown is a preferred arrangement that isolates the crossover groove  56  from contamination from the area near the surfaces between the valve  16  and the housing  12  at the radius of the external ports  42 ,  46 . 
     To fill the reaction vessel  18 , the piston  54  is pulled upward to draw the mixture in the reagent chamber  78  through the crossover groove  56  and the second branch  86  into the reaction vessel  18 . In such an arrangement, the reaction vessel  18  is the aspiration chamber or referred to as the first chamber, and the reagent chamber  78  is the source chamber or referred to as the second chamber. The valve  16  is then rotated to place the second external port  46  in fluidic communication with the first branch  84  and to close the first external port  42 , as shown in  FIGS. 9L and 9LL . The piston  54  is pushed downward to pressurize the mixture inside the reaction vessel  18 . The reaction vessel  18  may be inserted into a thermal reaction chamber for performing nucleic acid amplification and/or detection. The two branches  84 ,  86  allow filling and evacuation of the reaction chamber of the reaction vessel  18 . The vessel maybe connected to the housing  12  by ultrasonic welding, mechanical coupling, or the like, or be integrally formed with the housing  12  such as by molding. The use of a reaction vessel for analyzing a fluid sample is described in commonly assigned, copending U.S. patent application Ser. No. 09/584,328, entitled “Cartridge for Conducting a Chemical Reaction,” filed May 30, 2000. 
     To operate the valve  16  of  FIGS. 3-8 , a motor such as a stepper motor is typically coupled to the toothed periphery  29  of the disk portion  22  to rotate the valve  16  relative to the housing  12  for distributing fluid with high precision. The motor can be computer-controlled according to the desired protocol. A linear motor or the like is typically used to drive the piston  54  up and down with precision to provide accurate metering, and may also be computer-controlled according to the desired protocol. 
       FIG. 10  shows another valve  100  which is rotatably coupled to a fluid control channel housing or block  102 . A reaction vessel  104  is detachably coupled to the housing  102 . The valve  100  is a generally tubular member with a longitudinal axis  105  as shown in  FIG. 11 . A piston  106  is movably connected to the valve  100  to change the volume of the fluid displacement region  108  as the piston  106  is moved up and down. A cover  109  is placed near the bottom of the valve  100 . A fluid processing region  110  is disposed in the valve  100  and is in continuous fluidic communication with the fluid displacement region  108 . The valve  100  includes a pair of apertures serving as a first port  111  and a second port  112 , as best seen in  FIG. 11 . In the embodiment shown, the ports  111 ,  112  are angularly spaced by about 120°, but the spacing may be different in alternate embodiments. A crossover channel or groove  114  is formed on the external surface  116  of the valve  100  and extends generally in the longitudinal direction, as seen in  FIG. 10 . The two ports  111 ,  112  are disposed at different levels longitudinally offset from one another along the longitudinal axis  105 , and the crossover groove  114  extends in the longitudinal direction of the axis  105  bridging the two levels of the ports  111 ,  112 . 
     The housing  102  has an opening  118  for receiving the portion of the valve  100  having the ports  111 ,  112  and groove  114 . The internal surface  120  around the opening  118  is shaped to cooperate with the external surface  116  of the valve  100 . Although a gasket may be placed between the internal surface  120  and the external surface  116 , a preferred embodiment employs tapered or conical surfaces  120 ,  116  that produce a sealing effect without the use of an additional gasket. The housing  102  includes a plurality of channels and ports and the valve  100  is rotatable around its axis  105  to allow the ports  111 ,  112  to be placed selectively in fluidic communication with the plurality of channels in the housing  102 . Depending on which port is opened or closed and whether the piston  106  is moved upward or downward, the fluid flow in the valve  100  can change directions, and the ports  111 ,  112  can each switch from being an inlet port to an outlet port. 
     To demonstrate the fluid metering and distribution function of the valve  100 ,  FIGS. 12A-12N  illustrate the operation of the valve  100  for a specific protocol. As shown in  FIG. 12A , the housing  102  includes a plurality of fluid channels. For convenience, the channels are labeled as follows: reagent channel  130 , lysing channel  132 , sample channel  134 , wash channel  136 , waste channel  138 , first branch  140 , and second branch  142 . The channels  130 - 138  extend from the internal surface  120  to one external surface  144  which is generally planar, and the branches  140 ,  142  extend from the internal surface  120  to another external surface  146  which is also generally planar ( FIG. 10 ). When assembled, the first port  111  and the channels  130 - 134  lie on a first transverse plane that is perpendicular to the longitudinal axis  105 , while the second port  112 , the channels  136 ,  138 , and the two branches  140 ,  142  lie on a second transverse plane that is perpendicular to the longitudinal axis  105 . The second transverse plane is longitudinally offset from the first transverse plane. For convenience, the second port  112 , the channels  136 ,  138 , and the branches  140 ,  142  are shaded to indicate that they are longitudinally offset from the first port  111  and the channels  130 - 134 . The crossover groove  114  extends longitudinally to bridge the offset between the first and second transverse planes. A chamber body  150  is connected to the housing  102  ( FIG. 10 ), and includes the reagent chamber, lysis chamber, sample chamber, wash chamber, and waste chamber that are respectively coupled fluidicly with the channels  130 - 138 . The first and second branches  140 ,  142  are fluidicly coupled with the reaction vessel  104 . 
     In  FIG. 12A , the first port  111  is placed in fluidic communication with the sample channel  134  and the piston  106  is pulled upward to draw a fluid sample into the fluid displacement region  108  ( FIG. 11 ). The valve  100  is then rotated to place the second port  112  in fluidic communication with the waste channel  138  and the piston  106  is pushed downward to drive the fluid sample from the displacement region  108  through the processing region  110 , and out through the waste channel  138 , as shown in  FIG. 12B . These steps are typically repeated until an entire sample is processed through the processing region  110 , for instance, to capture sample components on a trapping member such as a filter. 
     In  FIG. 12C , the valve  100  is rotated to place the second port  112  in fluidic communication with the wash channel  136  to aspirate a wash fluid into the processing region  110  by pulling the piston  106  upward. The valve  100  is then rotated to place the second port  112  in fluidic communication with the waste channel  138  and the piston  106  is pushed downward to drive the wash fluid from the processing region  110  out through the waste channel  138 . The above washing steps can be repeated as desired to remove unwanted residue inside the valve  100 . 
     For lysing, the valve  100  is rotated to place the first port  111  in fluidic communication with the lysing channel  132  and the piston  106  is pulled upward to draw a lysing fluid into the fluid displacement region  108 , as shown in  FIG. 12E . In  FIG. 12F , the valve  110  is rotated to close both ports  111 ,  112 . The piston  106  is pushed downward to push the lysing fluid into the processing region  110  and to pressurize the lysing fluid and the sample components captured in the fluid processing region  110 . Additional energy may be applied to the mixture in the processing region  110  including, for instance, sonic energy transmitted into the processing region  110  by operatively coupling a sonic member with the cover  109  ( FIG. 11 ). 
     In  FIG. 12G , a desired preset amount of wash fluid is aspirated into the processing region  110  from the wash channel  136  through the second port  112  to dilute the mixture. The valve  100  is then rotated to place the first port  111  in fluidic communication with the reagent channel  130  to discharge a preset amount of the mixture from the processing region  110  to the reagent chamber, as shown in  FIG. 12H . The piston  106  is moved up and down to agitate and mix the mixture by toggling. The balance of the mixture is discharged through the second port  112  to the waste channel  138 , as shown in  FIG. 12I . Another wash is performed by drawing a wash fluid from the wash channel  136  through the second port  112  into the processing region  110  ( FIG. 12J ), and discharging the wash fluid from the processing region  110  through the second port  112  to the waste channel  138  ( FIG. 12K ). 
     In  FIG. 12L , the valve  100  is rotated to place the second port  112  in fluidic communication with the first branch  140  coupled to the reaction vessel  104 , while the second branch  142  which is coupled to the reaction vessel  104  is placed in fluidic communication with the crossover groove  114 . The second branch  142  is longitudinal offset from the reagent channel  130 . In the position as shown in  FIG. 12L , the crossover groove  114  extends longitudinally to bridge the offset between the second branch  142  and the reagent channel  130  to place them in fluidic communication with one another. As a result, the fluid processing region  110  is in fluidic communication, through the first branch  140 , the reaction vessel  104 , the second branch  142 , and the crossover groove  114 , with the reagent channel  130 . 
     By pulling the piston  106  upward, the mixture in the reagent chamber is drawn from the reagent channel  130  through the crossover groove  114  and the second branch  142  into the reaction vessel  104 . The valve  100  is then rotated to place the second port  112  in fluidic communication with the second branch  142  and to close the first port  111 , as shown in  FIG. 12M . The piston  106  is pushed downward to pressurize the mixture inside the reaction vessel  104 . In  FIG. 12N , the valve  100  is rotated to close the ports  111 ,  112  and isolate the reaction vessel  104 . The reaction vessel  104  may be inserted into a thermal reaction chamber for performing nucleic acid amplification and/or detection. 
     As illustrated in the above embodiments, the fluid control and processing system is advantageously a fully contained system that is versatile and adaptable. The fluid displacement region is the motivating force for moving fluid in the system. By maintaining a continuous fluidic communication between the fluid displacement region and the fluid processing region, the motivating force for moving fluid in the system is fluidicly coupled to the processing region at all times. The fluid displacement region (motivating force) also acts as a temporary storage area for the fluid being driven through the system. While the embodiments shown employ a moving piston in the fluid displacement region as the motivating force, other mechanisms may be used including, e.g., pneumatic pump mechanisms or the like which use pressure as the motivating force without a change in volume of the fluid displacement region. The inlet or outlet side of the fluid processing region can address any of the chambers to permit random access to reagents and other fluids. Complex protocols can be programmed relatively easily into a computer controller and then executed using the versatile fluid control and processing system. A myriad of different protocols can be performed using a single platform. 
     In the embodiments shown, the fluid control occurs by addressing a pair of ports in the valve to place only one port at a time selectively in fluidic communication with the chambers. This is accomplished by keeping the pair of ports out of phase relative to the chambers. A crossover or bypass channel provides additional fluid control capability (e.g., allowing convenient filling and emptying of the reaction vessel within the closed system). Of course, different porting schemes may be used to achieve the desired fluid control in other embodiments. Moreover, while the embodiments shown each include a single fluid processing region in the valve body, additional processing regions can be located in the valve body if desired. Generally, the valve body needs (n+1) ports per n processing regions. 
     The use of a single valve produces high manufacturing yields due to the presence of only one failure element. The concentration of the fluid control and processing components results in a compact apparatus (e.g., in the form of a small cartridge) and facilitates automated molding and assembly. As discussed above, the system advantageously includes dilution and mixing capability, intermediate wash capability, and positive pressurization capability. The fluid paths inside the system are normally closed to minimize contamination and facilitate containment and control of fluids within the system. The reaction vessel is conveniently detachable and replaceable, and may be disposable in some embodiments. 
     The components of the fluid control and processing system may be made of a variety of materials that are compatible with the fluids being used. Examples of suitable materials include polymeric materials such as polypropylene, polyethylene, polycarbonate, acrylic, or nylon. The various chambers, channels, ports, and the like in the system may have various shapes and sizes. 
     The above-described arrangements of apparatus and methods are merely illustrative of applications of the principles of this invention and many other embodiments and modifications may be made without departing from the spirit and scope of the invention as defined in the claims. 
     For instance,  FIG. 13  shows a soft-walled chamber  200  that may be incorporated into the fluid control and processing system. Typically, an on-board reagent style cartridge requires a total fluid volume of at least twice the total volume of reagents and sample combined in rigid systems. The use of soft-walled chambers can reduce the required volume. These chambers have flexible walls, and can typically be formed using films and thermoforming. An added advantage of soft walls is that venting need not be provided if the walls are sufficiently flexible to allow them to collapse when the chamber is emptied. In  FIG. 13 , a flexible sidewall  202  separates a reagent chamber  204  and a waste chamber  206 . Because the waste is composed of the sample and reagents, the volume required for waste is no more than the sum of the sample and reagents. The reagent chamber  204  contracts while the waste chamber  206  expands, and vice versa. This can be a closed system with no connection to the exterior. The configuration can reduce the overall size of the cartridge, and can allow fast change-overs of chamber volumes. It can also eliminate venting, and can cut costs by reducing the number of platforms that would otherwise need to be built with hard tooling. In one embodiment, at least two of the plurality of chambers in the system are separated by a flexible wall to permit change-over of chamber volumes between the chambers. 
       FIG. 14  shows a piston assembly  210  including a piston rod  212  connected to a piston shaft  214  having a smaller cross-section than the rod  212  for driving small amounts of fluids. The thin piston shaft  214  may bend under an applied force if it is too long. The piston rod  212  moves along the upper portion of the barrel or housing  216 , while the piston shaft  214  moves along the lower portion of the barrel  216 . The movement of the piston rod  212  guides the movement of the piston shaft  214 , and absorbs much of the applied force so that very little bending force is transmitted to the thin piston shaft  214 . 
       FIG. 15  shows a side chamber  220  that may be incorporated into the system. The side chamber  220  includes an inlet port  222  and an outlet port  224 . In this example, the side chamber  220  includes a filter  226  disposed at the inlet port  222 . Fluid is directed to flow via the inlet port  222  into the side chamber  220  and out via the outlet port  224  for side filtering. This allows filtering of a fluid sample or the like using the fluid control system of the invention. The fluid may be recirculated to achieve better filtering by the filter  226 . This prefiltering is useful to remove particles before introducing the fluid into the main chambers of the system to prevent clogging. The use of a side chamber is advantageous, for instance, to avoid contaminating the valve and the main chambers in the system. 
     A fluid sample may be introduced into the housing  12  of the fluid control and processing system  10 , which may be configured as a cartridge, by a variety of mechanisms, manual or automated. For manual addition, a measured volume of material may be placed into a receiving area of the housing  12  (e.g., one of the plurality of chambers) through an input port and a cap is then placed over the port. Alternatively, the receiving area may be covered by a rubber or similar barrier and the sample is injected into the receiving area by puncturing the barrier with a needle and injecting the sample through the needle. Alternatively, a greater amount of sample material than required for the analysis can be added to the housing  12  and mechanisms within the housing  12  can effect the precise measuring and aliquoting of the sample needed for the specified protocol. 
     It may be desirable to place certain samples, such as tissue biopsy material, soil, feces, exudates, and other complex material into another device or accessory and then place the secondary device or accessory into the housing causing a mechanical action which effects a function such as mixing, dividing, or extraction. For example, a piece of tissue may be placed into the lumen of a secondary device that serves as the input port cap. When the cap is pressed into the port, the tissue is forced through a mesh that slices or otherwise divides the tissue. 
     For automated sample introduction, additional housing or cartridge design features are employed and, in many cases, impart sample collection functionality directly into the housing. With certain samples, such as those presenting a risk of hazard to the operator or the environment, such as human retrovirus pathogens, the transfer of the sample to the housing may pose a risk. Thus, in one embodiment, a syringe or sipper may be integrated into the device to provide a means for moving a sample directly into the housing. Alternatively, the device may include a venous puncture needle and a tube forming an assembly that can be used to acquire a sample. After collection, the tube and needle are removed and discarded, and the housing  12  is then placed in an instrument to effect processing. The advantage of such an approach is that the operator or the environment is not exposed to pathogens. 
     The input port can be designed with a consideration of appropriate human factors as a function of the nature of the intended specimen. For example, respiratory specimens may be acquired from the lower respiratory tract as expectorants from coughing, or as swab or brush samples from the back of the throat or the nares. In the former case, the input port can be designed to allow the patient to cough directly into the housing  12  or to otherwise facilitate spitting of the expectorated sample into the housing. For brush or swab specimens, the specimen is placed into the input port where features of the port and closure facilitate the breaking off and retaining of the end of the swab or brush in the cartridge receiving area. 
     In another embodiment, the housing  12  includes one or more input tubes or sippers that may be positioned in a sample pool so that the sample material flows into the housing  12 . Alternatively, a hydrophilic wicking material can function to draw a sample into the device. For example, the entire cartridge can be immersed directly into the sample, and a sufficient amount of sample is absorbed into the wicking material and wicks into the housing  12 . The housing is then removed, and can be transported to the laboratory or analyzed directly using a portable instrument. In another embodiment, tubing can be utilized so that one end of the tube is in direct communication with the housing to provide a fluidic interface with at least one chamber and the other end is accessible to the external environment to serve as a receiver for sample. The tube can then be placed into a sample and serve as a sipper. Thus, the device may include a variety of features for collecting a sample from various different sources and for moving the sample into the housing  12 , thereby reducing handling and inconvenience. 
       FIG. 16  shows a fluid control and processing system  310  including a housing  312  having a plurality of chambers  313  wherein one of the chambers is a processing chamber  314 . The housing  312  includes a plurality of chamber ports  325  configured to communicate with a fluid control device such as a rotary fluid control valve similar to the rotary valve  16  in the system  10  of  FIGS. 1-4 . The valve has a fluid displacement region similar to the fluid displacement region  50  in the system  10 . The chambers  313  may include the same chambers as in the embodiment of  FIGS. 1-4  (i.e., sample chamber  60 , waste chamber  64 , wash chamber  66 , lysis chamber  70 , reagent chamber  78 , and reaction vessel  18 ). The housing  312  also includes a fluid processing region or active region similar to the fluid processing region  30  of system  10  in  FIGS. 1-4 . In such a configuration, the chamber ports  325  will face the external port surface of the disk portion of a rotary fluid control valve 
     The processing chamber  314  has a first port  326  and a second port  327 . In one example, the first port  326  may be an inlet port for taking in fluid, and the second port  327  may be an outlet port for discharging fluid from the processing chamber  314 . The processing chamber  314  typically is integrally formed or built into the main body of the housing  312 , so that the inlet and outlet ports of the processing chamber are two of the chamber ports. Alternatively, the processing chamber  314  may be formed as a separate member that can be inserted into the main body of the housing  312 , the inserted member having inlet and outlet ports that align with two of the chamber ports. 
     The processing chamber  314  may contain a processing chamber material, such as an enrichment material or medium or a depletion material or medium. An enrichment material captures a target such as an analyte from the fluid that passes through the processing chamber  314 . A depletion material traps or retains unwanted material from the fluid that passes through the processing chamber  314 . The enrichment or depletion material may comprise one or more solid phase materials. In general, the solid phase materials may include beads, fibers, membranes, filter paper, glass wool, polymers, and gels. 
     For example, enrichment materials may include chromatographic materials, more particularly absorptive phase materials, such as reverse phase materials, ion-exchange materials, or affinity chromatographic materials in which a binding member is covalently bound to an insoluble matrix. For the affinity chromatographic materials, the binding member may be group specific (e.g., a lectin, enzyme cofactor, Protein A and the like) or substance specific (e.g., antibody or binding fragment thereof, antigen for a particular antibody of interest, oligonucleotide and the like). The insoluble matrix to which the binding member is bound may be particles, such as porous glass or polymeric beads, networks of glass strands or filaments, a plurality of narrow rods or capillaries, and the like. For example, the insoluble matrix may include beads functionalized with antibodies for capturing antigens or haptens for an immunoassay procedure. 
     Instead of coated particles or other insoluble matrices, one may employ a coated/impregnated membrane which provides for selective retention of the analyte comprising fraction of a fluid sample while allowing the remainder of the sample to flow through the membrane and out of the processing chamber. A variety of hydrophilic, hydrophobic, and ion-exchange membranes have been developed for solid phase extraction. 
     Another example of an enrichment material is a gel medium, which can be used to provide for a diversity of different sieving capabilities. The enrichment channel through the processing chamber  314  serves to enrich a particular analyte comprising fraction of a liquid sample. By varying the pore size of the media, employing two or more gel media of different porosity, and/or providing for a pore size gradient, one can ensure that the analyte comprising fraction of interest of the initial sample is retained in the gel medium. 
     For some enrichment materials or depletion materials, it may be necessary to employ a retention mechanism to keep the particular material in the processing chamber. Frits such as glass frits may be used to retain the material in the processing chamber.  FIGS. 18-23  show two frits  330 ,  332  disposed inside the processing chamber  314 . In the embodiment shown, the frits  330 ,  332  are held in place by a retaining structure or member  336 . The retaining member  336  may be configured as a processing module or an insert that can be easily snapped into place in a receiving area of the processing chamber  314  and can be conveniently removed as desired. As shown in  FIG. 17 , in a specific embodiment, the processing chamber  314  includes a receiving area  329  for receiving a processing module containing an enrichment material or a depletion material. In other embodiments, the processing module may comprise a column containing a separation material or a structure containing a separation channel for capillary electrophoresis or isoelectric focusing. The processing chamber  314  has a collection area  331  for receiving fluid that has flowed through the processing module  336 . 
     Referring to  FIGS. 18-23 , the processing module  336  preferably includes a spout  333  that directs the fluid into the collection area  331 . The processing module includes a first frit  330  that is disposed adjacent the first port  326 , and the second frit  332  is spaced from the first frit  330  to provide a space  338  for the enrichment material or depletion material. In one embodiment, the fluid enters the processing chamber  314  through the first port  326 , passes through the first frit  330 , the enrichment material or depletion material in the space  338 , and the second frit  332 , and then by gravity flows to the collection area  331  of the processing chamber above the second port  327  and exits the processing chamber  314  through the port  327 . The space  338  serves as another fluid processing region. 
     In one example, a sample fluid is drawn from the sample chamber by rotating the valve to place the fluid displacement region in fluidic communication with the sample chamber via the first external port. This is illustrated for the system  10  of  FIGS. 1-4  in  FIGS. 9A and 9AA , which is generally the same as the system  310  of  FIGS. 16-23  except for the additional processing chamber  314  in the system  310 . The sample fluid bypasses the fluid processing region (region  30  in system  10 ), and enters the fluid displacement region (region  50  in system  10 ). The valve (valve  16  in system  10 ) is rotated to place the first external port in fluidic communication with the processing chamber  314 . The sample fluid is driven from the fluid displacement region into the processing chamber  314  via the inlet port  326 , bypassing the fluid processing region. As the fluid flows through the processing chamber  314  containing an enrichment material via the inlet port  326 , for example, the analyte comprising sample fraction will be retained by the enrichment material such as a chromatographic material in the processing chamber  314 . The remaining waste portion of the fluid is drawn out of the processing chamber  314  through the outlet port  327  and into the fluid displacement region of the valve by rotating the valve to place the first external port in fluidic communication with the outlet port  327  of the processing chamber  314 . The valve is then rotated to place the first external port in fluidic communication with the waste chamber (chamber  64  in system  10 ), and the waste fluid is driven from the fluid displacement region into the waste chamber. An elution liquid may then flow through the enrichment material in the processing chamber  314  to release the enriched sample fraction from the enrichment material and carry it from the processing chamber  314  to another chamber or another region such as an active region. The elution liquid may be first drawn into the fluid displacement region of the valve from another chamber, and then driven from the fluid displacement region into the inlet port  326  of the processing chamber  314  by manipulating the rotary valve. The elution liquid and the released enriched sample fraction may be drawn from the processing chamber  314  via the outlet port  327 , either into the fluid displacement region through the first external port (port  42  in system  10 ) bypassing the fluid processing region, or through the fluid processing region (region  30  in system  10 ) and into the fluid displacement region through the second external port (port  46  in system  10 ). The rotary valve may be further manipulated to transfer the fluid to other chambers or regions of the system  310 . 
     In another example a depletion material is provided in the processing chamber  314  for trapping or removing unwanted material from a sample fluid. The valve can be used to transfer the sample fluid from the sample chamber to the processing chamber  314  as described above. As the fluid flows through the processing chamber  314  containing a depletion material via the inlet port  326 , the unwanted materials such as cellular debris, contaminants, or amplification inhibitors are depleted from the fluid. The remaining fluid is drawn out of the processing chamber  314  through the outlet port  327  by rotating the valve to place the fluid displacement region in fluidic communication with the outlet port  327 . The fluid may be drawn through the second external port (port  46  in system  10 ) first into the fluid processing region (region  30  in system  10 ) and then into the fluid displacement region of the valve. Alternatively, the fluid may be drawn through the first external port (port  42  in system  10 ) into the fluid displacement region bypassing the fluid processing region. The fluid may subsequently be driven from the fluid displacement region into another chamber or region of the system  310  by manipulating the rotary valve. 
     Instead of solid phase materials, the processing chamber  314  may house liquid phase materials such as, for example, ficoll, dextran, polyethylene glycol (PEG), sucrose, and the like. 
     By providing one or more processing chambers in the fluid processing system  310 , the system  310  becomes more versatile, and is capable of performing additional steps of sample preparation other than those performed in the active region or processing region in the valve body (e.g., processing region  30  in  FIG. 8 ), to achieve multi-staged filtration, consecutive functions, and the like in a single device. Moreover, the processing chamber may be fluidicly coupled with an external fluid volume to facilitate large volume processing. The processing chamber may also be fluidicly coupled with an external chamber that contains materials that are not desirable inside the main body  312  of the fluid processing system  310 . 
     In general, the processing regions in the processing chambers (e.g., processing chamber  314  in  FIG. 16 ) and in the valve body (e.g., processing region  30  in  FIG. 8 ) may each contain enrichment materials or depletion materials. In some embodiments, each processing region may contain one or more such materials. For example, a filter (e.g., the filter or filter stack  27  in  FIG. 8 ) or beads may be placed in a processing region to remove unwanted materials such as cellular debris from the sample or for accomplishing concentration of cells. The filter or beads may be used to bind specific targets such as particular molecules in the sample, or to remove specific targets such as proteins, inhibitors, or the like. In some embodiments, a processing region includes a filter and another solid phase material such as beads, fibers, or wool, for molecular isolation of molecular targets or molecular removal of molecular materials. In other embodiments, a processing region may include different types of beads such as magnetic beads, glass beads, polymeric beads, and the like. The beads can be used for cell capture, cell lysis, binding of analyte, binding of unwanted material, or the like. In some embodiments, a single type of beads may be used to perform two or more of the functions of cell capture, cell lysis, binding of analyte, and binding of unwanted material. For instance, cells can be adhered to the beads and lysed to release their nucleic acid content, and the lysate together with the released nucleic acid can be moved to a separate region or chamber for further processing, leaving behind the beads and their adherent cellular debris. 
     In another embodiment, a separation channel is provided for performing capillary electrophoresis (CE), isoelectric focusing (IEF), or the like. This may be done before or after nucleic acid amplification. The separation channel may be a separate member that is inserted into a chamber of the fluid processing system, may be formed as a microchannel in the housing of the system, or may be built into one of the chambers of the system. 
       FIG. 24  shows a separation channel or region  350  in the fluid control and processing system  354 . The separation channel  350  is typically formed as a separate member that is assembled into the system  354  and may in some embodiments be disposed in a chamber  352 . Alternatively, the separation channel  350  may be integrally formed or built into the system  354 . The separation channel  350  may be a thin channel or a capillary coupled between at least two electrodes, which in the specific embodiment shown include two metal tubes  356 ,  358 . The lower end of the channel  350  is fluidicly coupled to a lower reservoir  361  which is fluidicly coupled to a chamber port or reservoir port  360 , while the upper end of the channel  350  is fluidicly coupled to a vented reservoir  362  provided in a support structure  366  for supporting the separation channel  350 . The metal tubes  356 ,  358  serve as electrodes to receive electrical energy and apply an electric field to the fluid in the separation channel  350 . Conductive wires in contact with the metal tubes  356 ,  358  may be molded into plastic and lead to respective contact areas on the external surface of the housing of the system  354 . A voltage source may then be connected to the contact areas to apply a voltage difference between the contact areas and thus between the electrodes. Alternatively, electrodes may be provided as part of an external instrument for applying the electric field, and be dipped into reservoirs at the ends of the separation channel  350 . The sample fluid is typically pumped by the piston  368  of the valve  370  from the fluid displacement region  372  through one of the external ports of the valve body (e.g., the external port  342 ) to the separation channel  350  via the reservoir port  360  and reservoir  361 . A sample plug is injected into the separation channel  350 , and the remaining portion of the sample fluid in the reservoir  361  may then be drawn via the chamber port  360  into the fluid displacement region  372  of the valve  370  by the piston  368 . The reservoir  362  may be used to introduce buffer, elution solvent, reagent, rinse and wash solutions, or the like into the electrophoretic flow path of the separation channel  350 . 
     Entities in the sample plug, such as molecules, particles, cells, and the like are moved through a medium contained in the separation channel  350  under the influence of the applied electric field. Depending on the nature of the entities (e.g., whether they carry an electrical charge), as well as the surface chemistry of the electrophoretic chamber in which the electrophoresis is carried out, the entities may be moved through the medium under the direct influence of the applied electric field or as a result of bulk fluid flow through the pathway resulting from the application of the electric field such as an electroosmotic flow. As the sample plug separates into species bands in the separation channel  350 , the bands are detected, for instance, optically by a single point detector disposed at a fixed location or by a scanning detector that scans along the length of the channel  350 . To facilitate optical detection, a portion of the housing may be optically transmissive or transparent. Alternatively, the detector may be inserted into the housing and placed adjacent the channel  350  (e.g., in a chamber which houses the channel  350 ). 
     Typically, separation is performed after amplification, for instance, using the method as described above in  FIGS. 9A-9LL . In one example, an amplified product (e.g., nucleic acid amplified by PCR) is introduced as the sample into the reservoir  361 . The separation channel  350  is prefilled with a separation material such a gel or buffer. A voltage is applied via the electrodes  356 ,  358  to inject a sample plug from the reservoir  361 . The rest of the sample is then removed from the reservoir  361 . Next, a buffer such as an electrolyte solution is introduced into the reservoir  361 . A voltage difference is applied between the electrodes  356 ,  358  to form an electric field that induces flow of a sample plug through the separation channel  350  and separates the sample plug therein into species bands, which are detected using, for instance, a single-point optical detector or a scanning detector. 
       FIG. 25  shows the valve  416  of another system  410  which has a housing with a plurality of chambers similar to the system  10  of  FIGS. 1-4 , except that the valve  416  has only one external port  442 . The valve  416  includes a valve body  420  having a disk portion  422  and a tubular portion  424 . The disk portion  422  has a generally planar external port surface  423 . The valve  416  is rotatable relative to the housing  412  of the system  410  (see  FIGS. 26A and 26AA ). The housing  412  includes a plurality of chamber ports facing the external port surface  423  of the disk portion  422  of the valve  416  to permit fluidic communication between the chambers of the housing  412  and the valve  416 . The disk portion  422  includes a fluid processing region  430 , a first flow channel  440  extending between the external port  442  and the fluid processing region  430 , and a second flow channel  438  extending between the fluid processing region  430  and a fluid displacement region  450  in the tubular portion  424  of the valve  416 . The fluid processing region  430  is in continuous fluidic communication with the fluid displacement region  450 . An outer cover  428  is placed over the fluid processing region  430 . The fluid processing region  430  may be used to subject a fluid flowing therethrough to various acoustical, optical, thermal, electrical, mechanical, or chemical processing. 
     As shown in  FIG. 25 , a fluid displacement member in the form of a plunger or piston  454  is movably disposed in the displacement region  450  of the tubular portion  424  to move up and down along the axis  452 . When the piston  454  moves upward, it expands the volume of the displacement region  450  to produce a suction for drawing fluid into the region  450 . When the piston  454  moves downward, it decreases the volume of the displacement region  450  to drive fluid out of the region  450 . As the rotary valve  416  is rotated around its axis  452  relative to the housing  412 , the external port  442  may be fluidicly coupled with one of the chambers or reaction vessel in the housing  412 . Depending on the action of the piston  454 , the external port  442  is either an inlet port or an outlet port. 
     To demonstrate the fluid metering and distribution function of the valve  416 ,  FIGS. 26A-26EE  illustrate the operation of the valve  416  for a specific protocol. In  FIGS. 26A and 26AA , the external port  442  is placed in fluidic communication with a sample chamber  460  by rotating the valve  416 , and the piston  454  is pulled upward to draw a fluid sample from the sample chamber  460  through the first flow channel  440 , the fluid processing region  430 , and the second flow channel  438  and into the fluid displacement region  450 . For simplicity, the piston  454  is not shown in  FIGS. 26A-26EE . 
     As shown in  FIGS. 26B and 26BB , the valve  416  is then rotated to place the external port  442  in fluidic communication with a storage chamber  470  which contains a lysing fluid (e.g., a lysing reagent or buffer). The piston  454  is pushed downward to transfer the fluid sample from the fluid displacement region  450  to the storage chamber  470 . The piston  454  is then pulled upward to draw the fluid sample and lysing fluid from the storage chamber  470  to the fluid displacement region  450 . The lysing fluid mixes with the sample and effects lysis of cell or viruses in the sample. Additional energy may be applied to the processing region  430  to assist the lysing process. For instance, a sonic member  476  such as an ultrasonic horn may be placed in contact with the outer cover  428  to transmit ultrasonic energy into the processing region  430  to facilitate lysing of cells or viruses of the fluid sample as the fluid flows from the fluid displacement region  450  to the storage chamber  470  and/or from the storage chamber  470  back to the fluid displacement region  450 . The outer cover  428  in one preferred embodiment is an interface wall which is dome-shaped or includes stiffening ribs. 
     In  FIGS. 26C and 26CC , the valve  416  is rotated to place the external port  442  in fluidic communication with a reagent chamber  478 , and the piston  454  is pushed downward to force the lysate to flow from the fluid processing region  430  to the reagent chamber  478 . The reagent chamber  478  typically contains reagents (e.g., PCR reagents and fluorescent probes) to be mixed with the fluid sample. The fluids are then mixed in the reagent chamber  478  by toggling the mixture between the fluid displacement region  450  and the reagent chamber  478  as the piston  454  is moved up and down. 
     In  FIGS. 26D, 26DD, and 26D ′D′, the valve  416  is rotated to place the external port  442  in fluidic communication with a first branch  484  coupled to the reaction vessel  418 , while the second branch  486  which is coupled to the reaction vessel  418  is placed in fluidic communication with the crossover groove  456 . The first branch  484  and second branch  486  are disposed at different radii from the axis  452  of the valve  416 , with the first branch  484  having a common radius with the external port  442  and the second branch  486  having a common radius with the crossover groove  456 . The crossover groove  456  is also in fluidic communication with the reagent chamber  478  ( FIG. 26D ), and serves to bridge the gap between the reagent chamber  478  and the second branch  486  to provide crossover flow therebetween. The external port is disposed within a range of external port radii from the axis and the crossover groove is disposed within a range of crossover groove radii from the axis, where the range of external port radii and the range of crossover groove radii are non-overlapping. Placing the crossover groove  456  at a different radius from the radius of the external port  442  is advantageous because it avoids cross-contamination of the crossover groove  456  by contaminants that may be present in the area near the surfaces between the valve  416  and the housing  412  at the radius of the external port  442  as a result of rotational movement of the valve  416 . 
     To fill the reaction vessel  418 , the piston  454  is pulled upward to draw the mixture in the reagent chamber  478  through the crossover groove  456  and the second branch  486  into the reaction vessel  418 . In such an arrangement, the reaction vessel  418  is the aspiration chamber or referred to as the first chamber, and the reagent chamber  478  is the source chamber or referred to as the second chamber. The valve  416  is then rotated to place the external port in fluidic communication with the first branch  484 , as shown in  FIGS. 26E and 26EE . The piston  454  is pushed downward to pressurize the mixture inside the reaction vessel  418 . The reaction vessel  418  may be inserted into a thermal reaction chamber for performing nucleic acid amplification and/or detection. The two branches  484 ,  486  allow filling and evacuation of the reaction chamber of the reaction vessel  418 . 
     The fluid control and processing system  410  of  FIGS. 26-26EE  is modified from the system  10  of  FIGS. 1-9LL  to provide only one external port. Similarly, the valve  100  of  FIGS. 10-12  may also be modified to provide only one external port by removing one of the two external ports  111 ,  112  and reconfiguring the fluid channels  130 - 138  and branches  140 ,  142  between the valve  100  and the various chambers and reaction vessel  104 . 
     The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents.