Abstract:
A system having a flow channel for conveying a sample and having fluid light guides for projecting light to the sample target area and collecting light from the sample target area. The system may have fluid light guides on or off the card containing the flow channel. Accurate alignment may be provided by the fluid light guides in lieu of requiring precise alignment for the light source and detectors. The flow channel may be part of a cytometer system.

Description:
BACKGROUND 
   The invention pertains to particle detection and analysis, and particularly to light impingement of particles and light scattering by particles. More particularly, the invention pertains to the guiding of light to and from such particles. 
   Patents and applications related to the present invention may include: U.S. Pat. No. 6,597,438, issued Jul. 22, 2003, and entitled “Portable Flow Cytometry”; U.S. Pat. No. 6,970,245, issued Nov. 29, 2005, and entitled “Optical Alignment Detection System; U.S. Pat. No. 5,836,750, issued Nov. 17, 1998, and entitled “Electrostatically Actuated Mesopump Having a Plurality of Elementary Cells”; U.S. patent application Ser. No. 11/027,134, filed Dec. 30, 2004, and entitled “Optical Detection System with Polarizing Beamsplitter; U.S. patent application Ser. No. 10/908,543, filed May 16, 2005, and entitled “Cytometer Analysis Cartridge Optical Configuration”; and U.S. patent application Ser. No. 10/908,014, filed Apr. 25, 2005, and entitled “A Flow Control System of a Cartridge”; all of which are hereby incorporated by reference. 
   The invention is a fluid mechanism for guiding light to a target and containing light scattered by the target. 

   
     BRIEF DESCRIPTION OF THE DRAWING 
       FIG. 1  shows an illustrative example of an on-card arrangement for fluid guiding of light to and from a flow channel on the same side of the flow channel; 
       FIG. 1   a  reveals cross-sectional views of a fluid light guide; 
       FIG. 2  shows an illustrative example of an on-card arrangement for fluid guiding of light to and from a flow channel on the opposite sides of the flow channel; 
       FIG. 3  shows an illustrative example of an on-card arrangement for fluid guiding of light to and from a flow channel both on the same side and opposite sides of the flow channel; 
       FIG. 4  shows an illustrative example of an off-card arrangement for guiding of light to and from a flow channel via an edge of a card; 
       FIG. 5  shows an illustrative example of an off-card arrangement for fluid guiding of light to and from a flow channel with the fluid guiding on another card; 
       FIG. 6  shows an illustrative example of an on-card arrangement for fluid guiding of light to and from a dual flow channel with fluid guiding on another card; 
       FIG. 7  shows an illustrative arrangement for fluid guiding of light to and from a flow channel approximately perpendicular to a larger surface side of a card; and 
       FIG. 8  shows an illustrative arrangement for fluid guiding of light to and from a flow channel to the larger surface side of a card with the fluid guiding on another but approximately perpendicular card. 
   

   DESCRIPTION 
   Application of the present invention may include use in a cytometer flow channel with laser light particle analysis. Laser light may be scattered by the particles in the flow channel to determine the presence and properties of a particle. For instance, information about brightness of the scattered light may be used to determine the size of a particle scattering the impinging light. However, there appears to be no reasonable and practical way in the art to accurately guide the light to an intersection of particles in the flow channel, for example, blood cells on a cytometer card flow channel. 
   The light may be confined to a channel on or off a card by controlling the flow of immiscible fluids with light from a VCSEL or other laser source being directed down a middle of the channel. By tapering the channel, it is possible to direct the light with the fluids into the flow channel to within a micron. It may also be possible to collect the scattered light into another flow channel that is precisely oriented to collect over only a certain angle. This light may then be similarly fluid guided and delivered to a detector mounted, for instance, on the card periphery. Herein, fluids may mean liquids and/or gases. 
   Fluidic channels may be formed in a card by micromachining or replica molding. This may be done at a high resolution of better than 0.1 micron. The flow channels for the blood and light may be in the same place. The vertical position may be fixed by an accurate positioning of all of the channels. 
   The detector may be positioned to pick up light at an angle relative to the flow stream in a channel. The fluids may guide the scattered light to the detector much like an optical fiber with transparent materials having different indices of refraction. The fluids similarly have different indices of refraction. 
   The pump for moving the fluids around the light in a structure for containing the fluids may likewise be off the card like the light source and the detector. However, the fluids for light control may come from a reservoir on the card. Also, the pump for the fluids may be on the card. The pump may be a micro pump such as a mesopump. The fluid reservoir, pump and fluid on a card may be designed for short duration use because the card may be thrown away. 
   The fluid control apparatus for detected light may be optional. The detector may pick up the scattered light at an angle relative to the direction of the impinging light. 
   Light transmission and detection may be to and from the edge of the card. The position of the light source and detector would be like looking into the edge of the card. 
   The fluids in a containing structure may have one fluid being like a sheath over another fluid. This fluid may have a laminar flow or layer like form relative to the other fluid. The flow of the fluids should have no turbulence, i.e., a low Reynolds number. 
   There may be a sort of self-registration with the laser and the detector. The fluid may be injected. The laser source and detector may be calibrated relative to each other on the card. Fluid control of the source light and detected light may be built into the card. Then an external laser and detector could just then be coarsely aligned relative to the card itself. The fluid control on or of the card may be used for precise alignment of the impinging and scattered light with the flow channel and detector, respectively. In conjunction with flow control, there may be a controller connected to the fluid pumps and other fluid control apparatuses. The fluid may be injected from the inside or outside according to the kind of light control desired. 
   The fluid control of light may be applied to a fluorescence scheme of a cytometer or other kind of particle analysis equipment. The laser and detection may be to and from via the edge of the card, or it may to and from a broad surface of the card. The idea of fluid control of the light is that two fluidic layers have an index of refraction difference and this traps the light inside the inner fluid where it can be directed precisely to a target, for example, in a cytometer or other card. Scattered light, for instance, may be directed to a detector via another channel. The location of the channels may make for precise determination on the card of the light paths. The flow channels and the light channel may be in the same plane of the card. 
   In a fluid light guide system  10  of  FIG. 1 , a laser  11  may provide a light beam  12  to a flow channel  13  on a card  14 . The light beam may impinge the flow channel  13  from the edge of card  14 . Flow channel  13  may contain a stream of particles  15  that may be detected and analyzed. One illustrative application of the present invention may be a cytometer. 
   A flow stream  16  with a single file of particles  15  moving through the flow channel  13  may be impinged with a laser light beam  12 . The particles  15  that are impinged by beam  12  may scatter some of the light  12  into scattered light  17  which may sensed by a detector  18 . 
   The light  12  from laser  11  may be shaped and controlled into a smaller beam that is sufficient to enter the small flow channel  13  containing the flow stream  16  having particles  15 . The light beam  12  may be focused or narrowed down with a fluid  21  around it. There may be a second layer of fluid  22  around the first layer of fluid  21 . Fluid  22  may have a sheathing effect on fluid  21 . These fluids may have a narrowing effect on the laser beam  12 . The may control the focus and the beam  12  direction to a very specific point such as a target area of a flow channel  13  where particles  15  can flow through and be impinged by a tightly focused beam  12 . The refractive indices of fluids  21  and  22  may be different. These fluids  21  and  22  of different indices proximate to each other in a concentric fashion may resemble an optical fiber designed to convey light. 
   Fluid  21  may enter a port  25  of a containing structure  26  which may have a window  27  for entry of laser beam  12 . The fluid  21  may move through container  27  toward the flow channel  13  of card  14 . The other fluid  22  may be brought into container  26  at an entry port  28  closer than port  25  to the flow channel  13 . Fluid  22  may be like a sheath that wraps around fluid  21 . Fluid  21  may be regarded as wrapping around beam  12 . Containing structure  26  may have a circular cross section and be cone-shaped. Container  26  may have a narrowing structure in a direction toward the channel  13 . That may cause the fluids  21  and  22  to narrow in toward the end  29  of container  26 . The beam  12  may be similarly narrowed as it approaches the end  29  of structure  26 . The fluids  21  and  22  may be diverted out of the structure  26  at the end  29  into an exit port  33 , which are returned to a reservoir  47 . Reservoir  47  may be segmented to hold fluids  21  and  22  together or separately, and if separately can be a resource of fluids  21  and  22  to reservoirs  44  and  46 , respectively, or a resource of fluids  21  and  22  for pumps  43  and  45 , respectively. On the other hand, fluids  21  and  22  may be returned directly from structure  26  to reservoirs  44  and  46 , respectively. The focused and narrowed beam may proceed out the end  29  through a window  34  into the flow channel  13 . Fluids  21  and  22  may be pumped into ports  25  and  28 , respectively, by the pumps  43  and  45 . Containing structure  26 , pumps  43  and  45 , and reservoirs  44 ,  46  and  47  may be situated in card  14 . The fluid shaping assembly for laser beam  12  may be referred to a fluid guided source sub-system  61 . 
   Light  17  is light  12  scattered by particles  15  in flow channel  13 , and exiting the flow channel, which may be controlled by a set of fluids  31  and  32  having different indices refraction in a fashion similar to fluids  21  and  22  but in a parallel concentric fashion which is different in that sense than the conical concentric fashion of fluids  21  and  22 . Fluid  31  may enter a port  35  which conveys the fluid to an elongated structure  36  having a cylindrical shape. The structure could have another shape. At an end of the structure  36  closest to the channel  13  may be a window  37  through which scattered light  17  from the flow channel  13  may enter. The light  17  may traverse the elongated structure  36  to the other end and exit the structure through a window  38 . Light  17  may go from structure  36  to a detector  18 . Fluid  31  may help contain the scattered light  17  into a more focused and controlled beam for reasons of more effective detection of the scattered light. Also, to assist in the containment of fluid  31  and light  17  is a fluid  32  having a different index of refraction than the index of fluid  31 . Fluid  32  may enter elongated structure  36  through a port  39 . 
   Fluid  32  may act as a sheath fluid around fluid  31  as the fluids flow through structure  36 , provide an effective concentric containment and guide light  17  in a manner like that of an optical fiber having two media as concentric layers of a core for containment and guidance of the light through the fiber. The fluids  31  and  32 , after traversing the length of elongated structure along with the light  17 , may exit the structure via ports  41  and  42  and enter reservoirs  48  and  49 , respectively. Pumps  51  and  52  may move the fluids  31  and  32 , respectively, through structure  36 . The fluids  31  and  32  may be returned to a common reservoir, separated into two compartments or not, like that for fluids  21  and  22 . Pumps  51  and  52  may be micro pumps, e.g., mesopumps, in the card  14 . The fluid shaping assembly for light  17  may be regarded as a fluid guided detection sub-system  62 . 
   The velocity and pressures of fluids  31  and  32  may be adjusted to provide a variable control and guidance of light  17 . The control of light  17  by the fluids  31  and  32  is not just for guiding the light but may be for self-registration and calibration. 
     FIG. 1   a  shows cross-sectional views of the dynamic fluid light guide mechanism  36 . The design and principle of mechanism as illustrated in this Figure may be similar to that of the dynamic fluid light guide structure or mechanism  26 . The dimensions  81  and  82  indicate the sheath or laminar barrier between the two fluids which may have different indices of refraction. The two fluids do not necessarily mix (i.e., immiscible) and may flow side by side with a smooth interface. Dimensions  81  and  82  may change in accordance with pressures and the velocities of the fluids  31  and  32 , respectively. Dimensions  81  and  82  may be increased or decreased relative to the dimensions as illustrated. Also, dimensions  81  and  82  may be different from each other, or may be varied relative to each other. At the input portion of the structure  36 , there may be a manifold or structural design so as, with fluids being input to ports  35  and  39 , to cause two or more concentric layers of the fluids to flow through mechanism  36 , the fluids having the same or various velocities and different indices of refraction. The inner (i.e., core) fluid  31  may have a higher index of refraction than the outer (i.e., sheath or cladding) fluid  32 . The inner fluid  31  may convey the light  17  and the outer fluid  32  may contain the light within the inner fluid. There may be a manifold or manifolds connected between external ports  35  and  39  and the body of mechanism  36  that distribute the fluids in a concentric volume manner or other fashion in the mechanism  36 . Also, there may be a manifold or manifolds that collect the fluids for removal via ports  41  and/or  42  from the mechanism  36 . Either end of mechanism  36  may be of another shape beside circular. Also, mechanism  36  may be of another design beside cylindrical. 
     FIG. 2  shows a fluid light guide system  20 . The fluid guided source sub-system  61  of system  10  may be used in system  20 . This system  20  may be similar to system  10  except that the fluid guided detection sub-system  63  of system  20  is positioned differently than the fluid guided detection sub-system  62  of system  10 . The sub-system  62  is positioned to collect light  17  from the same side of the channel  13  that the light source  11  and the light source sub-system  61  are situated. The sub-system  63  is positioned to collect light  17  from the opposite side of the channel  13  from where the light source  11  and the light source sub-system  61  are situated. However, the fluid guided sub-systems  62  and  63  are similar. 
     FIG. 3  shows a fluid light guide system  30 . This system  30  has a fluid guided source sub-system  64  that is similar to the fluid guided source sub-system  61  of systems  10  and  20 . The fluid guided detection sub-system  65  is positioned similarly as the fluid guided detection sub-system  62  of system  10 , that is, on the same side of channel  13  as the source sub-system. The fluid guided detection sub-system  66  may be positioned similarly as the fluid guided detection sub-system  63  of system  20 , that is, on the opposite side of channel  13  relative to the source sub-system. The detection sub-systems  65  and  66  and the source sub-system of system  30  are the same as the detection sub-systems  62  and  63  and the source sub-system  61  of systems  10  and  20 , respectively, except that the on-card sub-systems of system  30  do not necessarily have pumps and reservoirs situated in the card  14 . 
   System  40  of  FIG. 4  reveals a card  14  with a channel  13  for a flow  16  of a sample and particles  15  which may be impinged with light  11  from a laser  11 . Light  17  may be scattered by the particles  15  and detected by detector  18 . In a manner like that of systems  10 ,  20  and  30  of  FIGS. 1-3 , the light beams  12  and  17  may be controlled with fluid control sub-systems  67  and  68 , respectively. A difference between the sub-systems  67  and  68  and those of systems  10 ,  20  and  30  is that the sub-systems of system  40  are located off the card  14 . 
     FIG. 5  shows a system  50  that has sub-systems  67  and  68  like those of system  40  in  FIG. 4  except that sub-systems of system  50  are shown to be situated on another card  75  independent of card  14 . The sub-systems of system  40  are not necessarily situated on a card external to card  14 . 
     FIG. 6  shows a system  60  that has sub-systems  67  and  68  like those of system  50  of  FIG. 5  on a card  76  external to card  14 . System  60  may have a dual channel  13  for a flow stream  16  of particles  15  for analysis with impinging beams  12  from lasers  11  projected on both channels and resultant light  17  scattered by the particles  15 . The light  17  may be fluid-controlled by the sub-systems  68  and  71  and detected by the respective detectors  18 . Light beams  12  may be fluid-controlled by sub-systems  67  and  69 . Pumps and reservoirs for sub-systems  67 ,  68 ,  69  and  71  may be located on the card  76  or off the card. 
     FIG. 7  shows a system  70  that may have fluid-controlling sub-systems  72  and  73  for impinging light  12  to and scattered light from particles  15  in a flow stream  16  in an optical channel  13 . A difference between the sub-systems  72  and  73  relative to the like sub-systems of systems  10 ,  20 ,  30 ,  40 ,  50  and  60  of  FIGS. 1-6 , respectively, is that they are not necessarily situated in a plane parallel to a plane of the card  14 . The sub-systems  72  and  73  may be situated such that the impinging light  12  be directed to and the detected light  17  scattered by particles  15  in channel  13 , are in a plane about perpendicular to the planar surface of card  14 . Pumps and reservoirs for the sub-systems  72  and  73  may be situated proximate to these sub-systems. 
     FIG. 8  shows a system  80  having sub-systems  72  and  73  similar to those of system  70  of  FIG. 7  for fluid control of the projected beam  12  and detected beam  17 , to and from channel  13  of card  14 , respectfully. The sub-systems  72  and  73  of system  80  may be different from those of system  70  in that they may be situated in or on a card  77  that is not in the same plane as the planar surface of card  14  or is approximately perpendicular to the planar surface of card  14 . Another aspect of system  80  is that an additional detector  18  sub-system  74  may be situated to sense light  17  on the opposite side of the channel  13  which may be scattered or deflected by particles  15  in flow stream  16  or be straight through the channel  13 . The angles for detection of the light  17  may various ones. Such angles may be non-perpendicular or perpendicular to the planar surface  78  of card  14 . Pumps and reservoirs for the sub-systems  72 ,  73  and  74  may be on the card  77  or off-card. 
   In the present specification, some of the matter may be of a hypothetical or prophetic nature although stated in another manner or tense. 
   Although the invention has been described with respect to at least one illustrative example, many variations and modifications will become apparent to those skilled in the art upon reading the present specification. It is therefore the intention that the appended claims be interpreted as broadly as possible in view of the prior art to include all such variations and modifications.