Abstract:
The present invention provides a novel flow cytometry system having high sample cell throughput with simultaneous single and multi-parameter development, extraction and analysis. The invention is comprised of one or more analytic modules or chips aggregated into a stack or chain creating a common laser light transmission channel while maintaining a separate fluid sample flow path within each chip. Each flow chip includes an array of optical fiber light receivers. Each chip also includes integrated waveguides to receive and channel scatter, reflected or fluoresced light of specific frequency and wavelength to the optical fiber receiver. One or more waveguides and optical fiber receivers may be incorporated within each flow chip. Each sensing optical fiber delivers its received light emission to an electro-optical system signal processing module for measuring, digitizing and identifying the light signal.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     Priority is claimed to U.S. Provisional Application No. 60/645,787 filed Jan. 20, 2005, titled “MODULAR FLOW CYTOMETRY SYSTEM,” which is referred to and incorporated herein in its entirety by this reference. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT  
       [0002]     Not Applicable  
       SEQUENCE LISTING OR PROGRAM  
       [0003]     Not Applicable  
       FIELD OF INVENTION  
       [0004]     This invention relates to a system for analyzing parameters of microparticles based upon flow cytometry techniques. More particularly, this invention relates to such a system having modular and scalable components for enhanced sensitivity and ability to detect one or more parameters simultaneously from one or more fluid samples using a single laser light source.  
       BACKGROUND  
       [0005]     Flow cytometry involves the analysis of the fluorescence and light scatter properties of single particles, such as cells, nuclei and chromosomes, during their passage within a narrow, precisely defined liquid stream.  
         [0006]     A typical flow cytometer consists of several basic components: a light source, a flow chamber and optical assembly, photodetectors and processors to convert light signals into analog electrical impulses, analog-to-digital converters, and a computing system for analysis and storage of digitized data.  
         [0007]     Flow cytometers involve sophisticated fluidics, laser optics, electronic detectors, analog to digital converters, and computers. The electronics quantify faint flashes of scattered and fluoresced light. The computing system records data for thousands of cells per sample, and displays the data graphically.  
         [0008]     The fluidics of the cytometer hydrodynamically focus the cell stream to within an uncertainty of a small fraction of a cell diameter to cause the cell particles to travel sequentially in single file through the flow chamber portion of the cytometer. Various flow chamber configurations have been developed with differing flow velocities. Typically, the higher the flow velocity, the lower the sensitivity of the cytometer since each cell particle spends less time in the analytic portion of the flow chamber, providing less time to gather fluoresced and reflected light, and hence, less data useable for assessing the particular particle.  
         [0009]     The optical system of a flow cytometer focuses one or more laser beams on the target stream of cells passing through the flow chamber. Typically, the optics deliver laser light focused to a beam a few cell diameters across. The flow cytometer is cable of measuring various particle parameters based upon light scatter and light fluorescence created by the imposition of the laser light on each particle. Scatter parameters can provide indications of a cell&#39;s size, granularity, membrane complexity and number of organelles. Fluorescence parameters can provide information specific to the microparticle being studied, other than physical or geometric features. For example, proteins with specific antibodies may be detected, suggesting specific immunofluorescence. Also, DNA content may be measured to provide information concerning cell cycle and proliferation. Further, apoptis, mithochondrial function, oxidative bursts, reporter genes, glutathione/reductive reserve, Calcium ion flux, pH, cell division and conjugation, total protein content and cell-mediated cytotoxicity are additional examples of information that may be derived using flow cytometry.  
         [0010]     Flow cytometry uses electro-optical techniques to provide the quantitative analyses of various cell properties where the cells are sequentially studied in a continuous flow system. On the basis of the measured properties of each cell particle, the cells may then be physically isolated for their use in biological studies. Cells and subcellular constituents, such as chromosomes, can be analyzed and sorted. The greater the volume of data available for analyzing each cell as it passes through the cytometer flow chamber for subsequent sorting, the greater the ability to sort each cell according to specific features or properties.  
         [0011]     Flow cytometry is typically used in laboratory environments for biological and biomedical research and is also used in clinical data collection environments. However, in light of recent threats of bioterrorism, great interest has developed in creating cell detection systems possible of quickly identifying a potentially hazardous substance in a sample stream. Due to the size and cost of existing laboratory or clinically-based flow cytometry systems, they are not effective for use in a field triage setting where mobility is critical.  
         [0012]     Most current flow cytometry systems use the laser light source inefficiently. A single laser beam is focused on one sample cell stream as it passes through the flow chamber. The reflected or fluoresced light from each target cell is detected and transmitted through various optical band-pass filters. As the photonic response from each cell is transmitted through each filter, the signal strength of the collected photonic response is reduced. This signal strength reduction limits the number of sequential filters which may be applied to the signal before it is undetectable. Consequently, there is a limit to the number of parameters which may be analyzed for each target cell, generally four to seven. If the target cell is an unknown, this number is insufficient to quickly identify a target cell in a single pass through a typical flow cytometry system. In addition, the strength of various signal frequencies from a cell target can be insufficient to even be detected by available sensor technology. Consequently, a potentially relevant cell property may go undetected, thereby causing a researcher to miss a cell type relevant to the analysis.  
         [0013]     Consequently, a need exists for a system using flow cytometry methodology that is capable of measuring a plurality of parameters from a single target cell simultaneously without subjecting the target cell photonic response signal to a series of sequential band-pass filters causing the target response signal to quickly degrade.  
         [0014]     Further, a need exists for a cell detection system where target response signals may be simultaneously aggregated to increase the signal strength to a level sufficient to allow current detector technology to become aware of the presence of a particular particle of interest.  
         [0015]     Additionally, a need exists for a particle detection system capable of detecting smaller particles more expeditiously.  
         [0016]     And further, a need exists for a particle detection system capable of quickly identifying an unknown particle from an extensive list of known substances of interest in a non-laboratory environment.  
       OBJECTS OF THE INVENTION  
       [0017]     A first object of the invention is to provide a flow cytometry system with multiple light receivers embedded in a flow chip capable of simultaneously collecting light of differing frequencies reflected off target samples or fluoresced by target samples.  
         [0018]     A second object of the invention is to provide a flow cytometry system where the collected reflected or fluoresced light is not degraded or weakened for each additional parameter analyzed.  
         [0019]     A third object of the invention is to provide a capillary flow cytometry system having detection sensitivity equal to or greater than that of a fluid sheath flow cytometry system.  
         [0020]     A fourth object of the invention is to provide a flexible and scalable modular flow cytometry system where additional analytic elements or flow modules may be added in any combination to detect additional parameters of material in the carrier fluid or to increase the flow rate of particles of interest and hence, the sensitivity of the flow cytometry system.  
         [0021]     A fifth object of the invention is to provide an adaptable flow cytometry system whose physical size is small enough to be packaged in a hand-held device.  
         [0022]     A sixth object of the invention is to provide a flow cytometry system capable of detecting very small targets carried in the fluid sample at a very high flow rate.  
         [0023]     A seventh object of the invention is to provide a flow cytometry system capable of operation in a field or non-laboratory environment.  
         [0024]     An eighth object of the invention is to provide a micro-flow cytometry system where each individual module includes light receivers, filters and wave guides tuned to look for specific properties associated with the presence of a particular particle of interest. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0025]      FIG. 1  is a schematic diagram of the primary components of a flow cytometry system according to the present invention.  
         [0026]      FIG. 2  is a perspective view of an aggregation of a plurality of flow chip wafers according to the present invention.  
         [0027]      FIG. 3  is an exploded view of a stack of a plurality of flow chip wafers according to the present invention.  
         [0028]      FIG. 4  is a perspective view of an individual flow chip wafer according to the present invention.  
         [0029]      FIG. 5  is a perspective view of a half-wafer of an individual flow chip according to the present invention.  
         [0030]      FIG. 6  is a perspective view of the capillary flow chamber assembly of the flow cytometry system according to the present invention.  
         [0031]      FIG. 7  is a schematic of the multi-parameter processing capability of the flow cytometry system according to the present invention.  
         [0032]      FIG. 8  is a schematic of the single parameter processing capability of the flow cytometry system according to the present invention.  
         [0033]      FIG. 9  is a schematic of the combined single parameter and multi-parameter processing capability of the flow cytometry system according to the present invention.  
         [0034]      FIG. 10  is a schematic of the flow cytometry system according to the present invention wherein individual flow chips are connected via optical fibers. 
     
    
     SUMMARY OF THE INVENTION  
       [0035]     The present invention provides a novel flow cytometry system having high sample cell throughput with simultaneous single and multi-parameter development, extraction and analysis. The invention is comprised of one or more analytic modules or chips aggregated into a stack or chain creating a common laser light transmission channel while maintaining a separate fluid sample flow path within each chip.  
         [0036]     Each flow chip includes an array of optical fiber light receivers. Each chip also includes integrated waveguides to receive and channel reflected or fluoresced light of specific frequency and wavelength to the optical fiber receiver. One or more waveguides and optical fiber receivers may be incorporated within each flow chip. Each sensing optical fiber delivers its received light emission to an electro-optical system for measuring, digitizing and identifying the light signal.  
         [0037]     Aggregation of two or more flow modules allows simultaneous analysis of a single fluid sample for single or multiple parameters, or, simultaneous analysis of multiple fluid samples for single or multiple parameters. The analysis is accomplished using only a single laser light source to generate fluoresced, reflected or scattered light signals which are transmitted through corresponding wave guides or band pass filters or delivered directly to a fiber optic receiver to simultaneously identify multiple characteristics of the material contained in the sample passing through the common flow channel or to identify the presence of various materials within the fluid sample.  
         [0038]     Integrated Flow Stack and Aggregating Sensor Array  
         [0039]     The sensor array, through the combined use of a plurality of micro-mechanical wave guides and fiber optics receptors, creates multiple data collection points directly at the signal source adjacent the object of interest in the flow channel. In one configuration, the photons collected from the fiber sensor array are aggregated to increase sensitivity to a single parameter of interest. In another configuration, the collected photons remain segregated to identify a plurality of parameters simultaneously.  
         [0040]     The fiber optic sensor array is created using MEMS technology with 2D or 3D photolithography. The design of the present invention provides for miniaturization and mass production of the sensor/flow block.  
         [0041]     Multiple Channel-Single Laser Approach for Parallel Sampling  
         [0042]     In this embodiment, multiple sensor chips provide parallel, concurrent sample analysis using a single laser beam source. The laser light channel uses an optical fiber to carry the focused laser beam from the output end of the laser to the cytometer chip laser light channel. As the laser beam passes through each chip exciting various particles of interest, the beam is recollimated and focused via another optical fiber or optical lens. The recollimated and refocused beam is then used to excite target particles traveling through the sample flow conduit in the next chip. This continuous process allows parallel, simultaneous analysis of multiple samples using a single laser light source.  
         [0043]     Flexible Signal Detection Methods  
         [0044]     The photons collected from the fiber sensor array can be aggregated to increase overall sensitivity of the system to one or more parameters. Alternatively, each individual fiber may deliver its photon signal to a separate photonic sensor for identification of only one parameter. Alternatively, some fibers may deliver signals to a separate sensor while others are aggregated to increase sensitivity to a particular target of interest. Various types of readily available photonic sensors may be used to identify characteristics of interest in specific frequency ranges.  
         [0045]     Tunable-Laser Light Source  
         [0046]     In an alternative embodiment, the present invention&#39;s detection functionality may be further expanded by using a tunable laser as the primary light source to generate a plurality of laser light packets at varying frequencies to increase the number of potentially observable parameters. Various particles will fluoresce at different laser light frequencies. Additionally, where other particles are attached to targets within a sample, the laser light may be separately tuned to identify these other particles with known fluorescence frequencies and known affinity for attachment to specific particle types.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0047]     Referring to  FIG. 1 , a flow cytometry system  10  according to the present invention is comprised of a laser light source S connected to a power source E to generate a laser light beam L. The laser beam L passes through an optical focal lens  6 . A sample solution storage reservoir  8  delivers samples to a flow stack  20  containing at least one flow chip  30 . The flow chip  30  includes a centrally disposed flow chamber assembly  60 . A signal transmission optical fiber  80  transmits scattered and fluoresced optical signals from the flow chip  30  to a photonic signal processing and analysis module  90 .  
         [0048]     Referring to  FIG. 2 , the system  10  of the present invention includes a flow and detection module assembly, hereinafter, a flow stack  20 . The flow stack  20  is comprised of one or more flow chips  30 . A flow chip  30  includes a centrally-located laser light orifice  40  for receiving and transmitting the laser light beam. The flow chip  30  is laterally transected and bisected by a flow chamber cavity  50 , which intersects the laser light orifice  40 . The flow chamber cavity  50  receives and houses a capillary flow chamber assembly  60 . Integrated waveguides  70  are distributed about and penetrate the periphery of the flow chip  30  intersecting at the laser light orifice  40 . Optical fibers  80  are disposed to connect with the optical waveguides  70  and to connect to other external processing and analytical equipment.  
         [0049]     Referring to  FIG. 3 , an individual flow chip  30  is shown. The flow chip  30  is penetrated at its center by a laser light orifice  40 . A laser light recollection, collimation and focal lens  42  is aligned with the laser light orifice  40  and mounted on a discharge side of the flow chip  30 . The focal lens  42  recollimates, focuses and transmits the recollected laser beam L from a preceding flow chip  30  to the front side of the orifice  40  of a subsequent flow chip  30 . The flow chip  30  includes a flow chamber cavity  50  to receive a flow chamber assembly  60 . The flow chamber cavity  50  intersects the laser light orifice  40 . One or more waveguide channels  70  penetrate the flow chip  30  to intersect at the perimeter of the laser light orifice  40 . Optical fibers  80  extend from each waveguide channel  70  to transmit optical signals to external processing units.  
         [0050]     Referring to  FIG. 4 , a half wafer  32  of a flow chip  30  is shown. As illustrated, the flow chamber cavity  50  intersects the laser light orifice  40 . The flow chamber cavity  50  would generally have a diameter between 25 and 400 micrometers, depending on the size of a flow chamber assembly  60  to be used based on the size of particles of interest to be analyzed. One or more waveguide channels  70  penetrate the flow chip  30  from its edges to intersect at the periphery of the laser light orifice  40 . A complete flow chip  30  is comprised of two half wafers  32 . Once the two half wafers  32  are assembled, the capillary flow chamber  60  will lay centered in the chip flow chamber cavity  50  with a cellulitic flow sheath  62  of the flow chamber assembly  60  located adjacent to the laser light orifice  40 . A midline of the cellulitic flow sheath  62  is aligned with a center axis of the laser light orifice  40 . Optical fibers  80  will be connect with the optical waveguide pathways  70 . Two flow chip wafer halves will be bonded together to form a complete individual flow chip  30 , housing the flow chamber  60  centrally disposed within the flow chamber cavity  50 , forming the waveguides  70  and securing the optical fibers  80 . A recollimation lens  42  (not shown) is centrally mounted in the laser light orifice  40  on the discharge side of the wafer half  32  of the flow chip  30 .  
         [0051]     Referring now to  FIG. 5 , a flow chamber assembly configuration  60  of the system  10  of the present invention is shown. The flow chamber  60  includes a cylindrical cellulose sheath  62 . The sheath  62  is wrapped around a glass capillary tubing  64 . The refractive index of the sheath  62  and the capillary tubing  64  are essentially equivalent to prevent distortion of any scattered or fluoresced light generated by the excitation of any particles of interest P. The capillary tubing  64  includes a capillary flow conduit  66  which receives the fluid sample carrying the particles of interest P. The flow chamber  60  is centrally disposed within the flow chamber cavity  50  with the cellulose sheath  62  aligned at its midline with the laser light orifice  40 . The flow conduit  66  of the capillary tubing  64  of the flow chamber assembly  60  is sized to receive a fluid sample containing particles of interest P of a particular size, ensuring that the particles P travel in single file as they pass through the flow chamber  60 , causing each particle P to be individually excited by the laser light beam L.  
         [0052]     Referring now to  FIG. 6 , the flow stack  20  of the system  10  of the present invention is described in greater detail. As illustrated in an exploded view, in the flow stack  20 , an initial laser light beam L is first targeted at the laser light orifice  40  of the first flow chip  30  of the stack  20 . As the laser beam L passes through the laser light orifice  40  of the first chip  30 , the beam L passes cellulose sheath  62  and the capillary tubing  64  of the flow chamber assembly  60  to impinge upon and excite various particles of interest P traveling through the capillary flow conduit  66 . In the present invention, the refractive index of the cellulose sheath  62  and the capillary tubing  64  are selected so as to be essentially equivalent to the refractive index of the sample solution to minimize distortion of both the laser beam L and any reflected or fluoresced light signal generated by an excited particle. However, some distortion of the beam L will occur as it travels through the illumination zone of each flow chip  30 . A recollimation lens  42  centrally disposed within the laser light orifice  40  on the discharge side of a flow chip  30  collects and recollimates the distorted initial laser light beam L to form a recollimated light beam R. The recollimated light beam R is then delivered to the next flow chip  30  where it once again impinges upon and excites particles of interest P traveling through the flow chamber  60  of that flow chip  30 . As shown in  FIG. 6 , the process of applying the laser beam L to each flow chip  30  and then recollimating the beam R for use in the next flow chip  30  can continue for as many flow chips  30  and individual fluid samples for so long as there is sufficient energy in the recollimated beam R to excite potential particles of interest P.  
         [0053]     Referring once again to  FIG. 2  and  FIG. 3 , although the flow chip  30  is shown for simplicity as shaped in a flat square for use in a stack configuration  20 , a flow chip  30  may be formed in any shape as long as a rear surface of a first flow chip  30  is able to mate with the front surface of a subsequent flow chip  30  to properly align the laser light orifices  40  of both chips. In any flow stack  20 , the individual flow chips  30  are coupled so as to accurately align each individual laser light transmission orifice  40  to allow transmission of a single laser light beam L through multiple flow chambers  60  in multiple flow chips  30 .  
         [0054]     Likewise, although the laser light orifice  40  is shown in  FIG. 4  as being located in the center of the square flow chip  30 , one skilled in the art will recognize that the laser light orifice  40  may penetrate the chip  30  at other locations rather than the center without disturbing the function of the system  10  as long as the flow chamber cavity  50  and the laser light orifice  40  remain aligned to intersect and create a particle excitation zone.  
         [0055]     Referring once again to  FIG. 6 , the laser light orifice  40  is sized to receive a laser beam L. An input side  41  of the orifice  40  carries the laser beam L to impinge on a target particle of interest P present in the flow chamber  60  adjacent the orifice  40 . An output side  42  of the orifice  40  includes a recollimation lens  44  which refocuses and transmits the laser beam L to a corresponding input side  41  of the orifice  40  of a subsequent flow chip  30 . Once again, the laser light L illuminates target particles of interest P present in the flow chamber  60  of the subsequent flow chip  30 .  
         [0056]     Referring now to  FIG. 7 ,  FIG. 8  and  FIG. 9 , a schematic diagram of the system  10  of the present invention with the various signal processing configurations and associated methodology are described.  
         [0057]     Multi-parameter Signal Processing Configuration and Method  
         [0058]     Referring to  FIG. 7 , the primary components of the system  10  are illustrated and the method of multi-parameter processing of output signals is described. A sample solution reservoir  8  delivers a fluid sample and entrained target particles of interest P to the system flow chamber  60  centrally disposed within the flow chip  30 . As each particle P travels through the flow chamber  60 , it eventually passes through the portion of the flow chamber  60 , the illumination zone, which is illuminated by the laser beam L and located adjacent the laser light orifice  40  of the flow chip  30 . When each particle P passes through the illuminated zone of the flow chamber  60 , the particle P is energized in some manner by the laser beam L to create either scattered or fluoresced light. The output light signal is then captured by the various waveguides  70  distributed about the perimeter of the laser light orifice  40  of the flow chip  30 . Each waveguide  70  is tuned to a light signal of a particular frequency. If the energized particle P emits a signal of the frequency specific to a particular waveguide, the signal is transmitted via the waveguide  70  to a collection optical fiber  80  and then to the signal processing module  90  where it is then delivered directly to its associated parameter processing unit  92  specific to the waveguide  70  frequency.  
         [0059]     As shown in  FIG. 7 , the multi-parameter processing methodology of the present invention  10  provides for capturing ten distinct photonic signals from each energized particle P. Ten separate waveguides  70  are designed to capture  10  distinct light signal frequencies which are then delivered to ten distinct parameter processing units  92 . Consequently, as each individual particle P is energized, the system  10  is capable of analyzing the particle for ten distinct parameters simultaneously and in parallel.  
         [0060]     When configured in a stack  20  as illustrated in  FIG. 1 ,  FIG. 2 , and  FIG. 6 , the output signals of each flow chip  30  may be processed by the same signal processing unit  90 . Consequently, the output of each flow chip  30  may be aggregated with the output of every other flow chip  30 , increasing the detection sensitivity of the overall system  10 , specific to the particular parameters of interested defined by the waveguides  70 .  
         [0061]     Once light signals have been delivered and then processed by the signal processing module  90 , the output data is transmitted to an external device capable of displaying or storing the data in a usable form. The external device may be the display of a hand-held personal digital assistant, the display of a desktop computer, the display of a lap top computer, and various forms of digital storage devices.  
         [0062]     In another configuration, instead of waveguides  70 , the flow chips  30  will simply have optical fibers  80  disposed about the perimeter of the laser light orifice  40  of the chip  30 . In this configuration, the light signal is not preprocessed by waveguides  70  incorporated within the chip  30 , but instead, is delivered in raw, unprocessed form to external processing devices. External processing devices may include other types of waveguides, band-pass filters or other analytic devices used for processing light signals.  
         [0063]     Aggregated Single Parameter Signal Processing Configuration and Method  
         [0064]     Referring now to  FIG. 8 , the system and method of single parameter processing of aggregated signals according to the present invention is described.  
         [0065]     A sample solution reservoir  8  delivers a fluid sample and entrained target particles of interest P to the system flow chamber  60  housed in the flow chip  30 . As each particle P travels through the flow chamber  60 , it eventually passes through the portion of the flow chamber  60  illuminated by the laser beam L adjacent the laser light orifice  40  of the flow chip. When each particle P passes through the illuminated portion of the flow chamber  60 , the particle P is energized in some manner by the laser beam L to create either scattered or fluoresced light. The output light signal is then captured by the various waveguides  70  distributed about the perimeter of the laser light orifice  40  of the flow chip  30 . For single parameter processing, each waveguide  70  is tuned to a single light signal of a particular frequency. If the energized particle P emits a signal of the frequency specific to the waveguide, the signal is transmitted via the waveguides  70  to the collection optical fibers  80  and then to the signal processing module  90  where it is then delivered directly to its associated single parameter processing unit  92 .  
         [0066]     In the single-parameter configuration illustrated in  FIG. 8 , the single-parameter processing methodology of the present invention  10  provides for capturing a distinct photonic signal of the same frequency from ten separate collection points distributed about the perimeter of the laser beam orifice  40  for each energized particle P. These ten distinct signals of the same frequency may then be aggregated in one parameter processing unit  92  to maximize the intensity of the specific signal and enhance the sensitivity of the overall system  10 .  
         [0067]     Combined Multi-Parameter and Single Parameter Signal Processing Configuration and Method  
         [0068]     Referring now to  FIG. 9 , the system and method of simultaneous multi-parameter and single parameter processing of signals according to the present invention is described.  
         [0069]     A sample solution reservoir  8  delivers a fluid sample and entrained target particles of interest P to the system flow chamber  60  housed in the flow chip  30 . As each particle P travels through the flow chamber  60 , it eventually passes through the portion of the flow chamber  60  illuminated by the laser beam L adjacent the laser light orifice  40  of the flow chip. When each particle P passes through the illuminated portion of the flow chamber  60 , the particle P is energized in some manner by the laser beam L to create either scattered or fluoresced light. The output light signal is then captured by the various waveguides  70  distributed about the perimeter of the laser light orifice  40  of the flow chip  30 .  
         [0070]     As shown in  FIG. 9 , five of the waveguides  70  are tuned to different signal frequencies and deliver their signals to five different signal parameter processing units  92  within the signal processing module  90 . The other five waveguides  70  are tuned to a sixth frequency and all five collected signals are delivered to a sixth single parameter processing unit  92  of the processing module  90 .  
         [0071]     In this manner, the system  10  of the present invention can be configured to maximize sensitivity to a single identified parameter while still maintaining sensitivity to other distinct parameters. As in the other described configurations for multi-parameter and single parameter processing, combining multiple flow chips  30  in a stack  20  will allow a user to both increase sensitivity to a single parameter, to multiple parameters, or to maximize the number of parameters detected in a single detection device.  
         [0072]     Referring now to  FIG. 10 , in an alternative embodiment  100 , the flow cytometry system according to the present invention is described. The alternative embodiment  100  is comprised of a plurality of flow chips  30  where the flow chips  30  are not stacked immediately adjacent one another, but instead are connected by separate optical transmission, recollection and recollimation fibers  44 . The laser light beam L is delivered to the first flow chip  30  by an initial laser beam delivery optical fiber  9 . As the laser light beam L passes through each chip  30 , the beam L is recollimated by a recollimation lens  42  and then delivered to the next flow chip  30  via a collection and recollimation optical fiber  44 . In this embodiment, the flow chips  30  may be arranged in other configurations other than a stack configuration  20 . This will allow flexibility in the design of hardware systems used to house the flow cytometry package.  
         [0073]     While the foregoing has been with reference to particular embodiments of the invention, it will be appreciated by those skilled in the art that changes in these embodiments may be made without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and the preceding descriptions.