Abstract:
A miniature pump has at least one controllable expansion-and-contraction chamber, and associated pair of tiny ducts interconnecting a fluid source and destination. The ducts communicate with the chamber(s); an linking tunnel links the ducts. Valves interact with fluid pressures due to expansion and contraction, imposing directionality on flow in the ducts and tunnel. Preferences: making the valve a passive flapper, implanting the pump in a creature, making the source a medication reservoir for supplying the creature; making the source a fuel tank and destination a tiny engine; making the source provide a specimen for assay and destination an observation slide; human or automatic examination of the slide under a microscope (e. g. electron microscope); making the source a reagent and destination a process stream; making the source a colorant and destination a colorant application system. Preferably included is an optical channel with intersecting fluid duct for optically monitoring pumped fluid.

Description:
RELATED PATENT DOCUMENT  
       [0001]     This patent document claims priority from provisional application 60/327,759, filed Oct. 5, 2001.  
         [0002]     Wholly incorporated by reference herein are copending, coowned provisional applications Ser. 60/228,883 and 60/327,760. The first of these applications later became the basis of U.S. patent application Ser. No. 10/142,654—which issued Feb. 15, 2005 as U.S. Pat. No. 6,856,718; and the second (a companion case to this one) became U.S. patent application Ser. No. 10/265,278—eventuating as issued U.S. Pat. No. 6,934,435. 
     
    
     BACKGROUND  
       [0003]     There has been an ongoing research effort to integrate microfluidic-based systems with appropriate sensors and analytical components. An objective has been effective miniaturization of chemical and biological assays, with the creation of a lab-on-a-chip technology.  
         [0004]     A defining attribute of microassays is small amounts of gas or liquid material required for sample reaction. This economy of scale affords the ability to test more compounds or drug candidates for a desired or undesired reaction.  
         [0005]     In addition, microreaction technology offers efficient heat transfer and the potential for optimized mixing and safer processing—in other words, better reaction control, as well as reduced waste. Because both the sample size and the reaction quantities are so small, multiple individual assays can be run in parallel, affording more reliable results.  
         [0006]     Such reaction systems are amenable to construction in a parallel fashion to increase throughput. Alternatively, specimens can be attached to parallel systems to allow simultaneous performance of multiple different assays.  
         [0007]     While many companies have brought the lab-on-a-chip technology to the forefront of microelectromechanical system (MEMS) applications, these developments heretofore have failed to fully integrate the pumping and detection functions. An a result, none of these earlier efforts can achieve major advances in either miniaturization or biomedical applications.  
         [0008]     It is not intended to unduly criticize such prior work, which is noteworthy and admirable. Nevertheless it does leave room for refinement.  
       SUMMARY OF THE INVENTION  
       [0009]     The present invention provides such refinement, partly by introducing a now aspect of microfluidics and sample mixing. The present section of this document will first offer an informal introduction, which is not to be taken as limiting the scope of the invention; and then a perhaps-more-rigorous summary.  
         [0010]     This innovation combines a pumping mechanism and detection mechanism in the same substrate. Certain preferred embodiments of the invention include a microfluidic pump, diaphragm membrane, waveguide-based optical crossconnect, and an actuator substrate. The optical crossconnect is detailed in the above-mentioned patent documents.  
         [0011]     Integrating the reciprocating microfluidic pump system of this invention into a microchip allows the invention to be applied to both chemical and biological assays. The microfluidic pump (or “micropump”) system essentially combines the benefits of miniaturization, integration and automation while also solving complex design problems such as controlling and directing sample flow at intersections of micron scale.  
         [0012]     The micropump can use multiple columns and chambers. It is advantageous in that it allows samples to accumulate and mix through a fluid path—and thus allows longer column lengths and continuous detection. Thereby the invention enhances the potential for more accurate data averaging.  
         [0013]     Certain preferred embodiments of the invention incorporate a planar silicon, silica or polymer waveguide, with a chemical/biological sampling chip utilizing certain of the elements in the prior MEMS-based all-optical switch technology. Apparatus according to the invention can include a nonblocking planar-waveguide-based switch, or switch array, such as the “fluid-based actuator-stroke amplification” system (“FASA”) which is taught in the first above-mentioned patent—and which may also be called a switch “fabric”.  
         [0014]     Given the foregoing informal orientation, a more-formal summary follows:  
         [0015]     In preferred embodiments of its first major independent facet or aspect, the invention is a miniaturized fluid pump system that includes a substrate and at least one controllable expansion-and-contraction chamber formed in the substrate. Also included are a pair of substantially microscopic ducts, respectively communicating with a fluid source and a fluid destination—and at least one of the ducts communicating with the chamber.  
         [0016]     In addition the first main aspect or facet of the invention includes a linking tunnel, distinct from the chamber, formed in the substrate and communicating with both ducts. (It may be noted that the distinctness of this tunnel from the chamber sets the invention apart from that of e. g. Tani, U.S. Pat. No. 6,164,933, in which the only cross-tunnel is identical with the chamber itself.) It also includes at least one exclusively passive valve interacting with fluid pressures due to expansion and contraction, respectively, to impose a directionality upon fluid flow in the ducts and tunnel.  
         [0017]     The foregoing may represent a description or definition of the first aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.  
         [0018]     In particular, by including a linking tunnel and passive rather than active valves (as in, e. g., Smits, U.S. Pat. No. 4,938,742), the overall pumping operation is essentially slaved to expansion and contraction of the chamber. This very greatly simplifies electrical connections, synchronization requirements etc. and thereby renders the system far more efficient.  
         [0019]     Although the first major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, preferably the at least one exclusively passive valve is a passive flapper.  
         [0020]     Another primary preference is that the substrate be implanted within a living creature. If this main preference is observed, then two subpreferences are that the fluid source be a chamber for medication to be delivered to the creature; and also that the chamber be implanted within the creature.  
         [0021]     Another preference is that the fluid source be a fuel tank; and the fluid destination be a substantially microscopic engine. Yet another preference is that the fluid source provide a specimen for assay; and the fluid destination be a slide for observation.  
         [0022]     Still another main preference is that the invention encompass the pump system in further combination with a microscope; in this case the slide is for human observation under the microscope. If this main preference is observed, then a subpreference is that the microscope be an electron microscope.  
         [0023]     A still-further preference is that the invention encompass the pump system in further combination with some means for automatic examination. (For purposes of generality and breadth in discussing the invention, these means may be called simply the “automatic-examination means”.) The slide is for automatic examination by the automatic-examination means. Two alternative preferences are that the fluid source be a reagent and the fluid destination a process stream; and that the fluid source be a colorant and the fluid destination be a colorant application system.  
         [0024]     Another particularly noteworthy preference is that the invention encompass the pump system in further combination with an optical monitoring device. The monitoring device includes a monitoring-device substrate, and formed in that substrate a channel for passage of an optical signal.  
         [0025]     Intersecting the optical-signal channel is a column for movement of fluid into and out of the optical-signal channel. These provisions are for optical monitoring of the fluid—particularly, where applicable, the fluid pumped by the pump system.  
         [0026]     If this particularly noteworthy preference is observed, then several subpreferences arise: first, it is best that the combined pump system and monitoring device further includes some means for displacing fluid along the column to control placement of the fluid relative to the optical-signal channel, for optical monitoring of the fluid.  
         [0027]     A second subpreference is that the displacing means include another controllable expansion-and-contraction chamber, formed in the monitoring-device substrate and communicating with the column. Still another subpreference, also applicable to the two subpreferences just stated and especially useful, is that the monitoring-device substrate be substantially integrated with the pump-system substrate.  
         [0028]     In preferred embodiments of its second major independent facet or aspect, the invention is a method for moving a fluid from a fluid source to a fluid destination. The method includes disposing the fluid in a miniaturized fluid pump system that comprises: 
        a substrate,     at least one controllable expansion-and-contraction chamber formed in the substrate,     at least two substantially microscopic ducts, communicating with the fluid source and with the destination,     at least one linking tunnel, distinct from the chamber, formed in the substrate and aligned with at least two of the ducts, and     at least one exclusively passive valve interacting with fluid pressures due to expansion and contraction, respectively. 
 
 The passive valve, in particular, operates to impose a directionality upon fluid flow in the at least one chamber and the at least two ducts. 
       
 
         [0034]     The method of this second main aspect of the invention also includes the step of controlling expansion and contraction in the at least one chamber. This controlling stop drives fluid from the source to the destination.  
         [0035]     The foregoing may represent a description or definition of the second aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.  
         [0036]     In particular, this method aspect of the invention enjoys the same advantages mentioned above, relative to Smits and Tani (for example), with respect to the passive valves as well as the tunnel distinct from the active chamber.  
         [0037]     Although the second major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, preferably the method further includes the step of observing a specimen of the fluid. In this case the source provides the specimen for assay, and the fluid destination is a slide for observation.  
         [0038]     If the foregoing primary preference is observed, then a subpreference is that the observing step comprise observation under a microscope, and the slide be for human or machine observation under a microscope. Here an alternative subpreference is that the observing step comprise observation under an electron microscope, and the microscope be an electron microscope for human or machine observation of the specimen.  
         [0039]     In preferred embodiments of its third major independent facet or aspect, the invention is a miniaturized fluid pump system that includes a substrate having at least one generally planar surface. Also included is at least one controllable expansion-and-contraction chamber formed in the substrate.  
         [0040]     This third facet of the invention also includes a first microscopic straight duct formed in the substrate and intersecting the surface substantially at right angles, and communicating directly with the chamber. It also includes a second substantially straight duct formed in the substrate substantially parallel to the first duct and also intersecting the surface. One of these ducts communicates with a fluid source and the other of the ducts communicates with a fluid destination.  
         [0041]     Also included is a linking tunnel, distinct from the chamber, formed in the substrate substantially parallel with the surface and communicating with both ducts. Further included is at least one valve associated with each of the ducts, respectively, and interacting with fluid pressures due to expansion and contraction to impose a directionality upon fluid flow in the ducts and tunnel.  
         [0042]     The foregoing may represent a description or definition of the third aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.  
         [0043]     In particular, the geometry just described imparts to this aspect of the invention an extremely beneficial simplicity and ease of manufacture. The invention is thereby made particularly economic.  
         [0044]     Although the third major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, preferably each of the at least one valves is an exclusively passive valve.  
         [0045]     Also applicable to this third main facet of the invention are the preferences mentioned earlier, particularly in connection with the first aspect of the invention—and in related to incorporation of an optical monitoring device with the pump. As before, the monitoring device preferably includes a monitoring-device substrate having a channel formed in it for passage of an optical signal; and, intersecting the optical-signal channel, a column for movement of fluid into and out of the optical-signal channel.  
         [0046]     The monitoring-device substrate and column are for optical monitoring of the fluid. The several other preferences previously mentioned in this regard also apply here.  
         [0047]     The foregoing benefits and advantages of the invention will be more fully appreciated from the following Detailed Description of Preferred Embodiments, considered in conjunction with the appended illustrations—of which: 
     
    
     BRIEF DESCRIPTION OF THE ILLUSTRATIONS  
       [0048]      FIG. 1  is a diagram, highly schematic, including complementary plans (A views, above) and elevational cross-sections (B views, below)—the latter very greatly enlarged—of a light-switch fabric;  
         [0049]      FIG. 2  is a set of three photographs—the left-hand “A” view being a natural perspective view of a 250:1 scale model prototype apparatus in which a form of the invention was reduced to practice; the center “B” view being an actual image produced by the apparatus with the actuator relaxed, and accordingly showing total internal reflection of the beam at the column; and the right-hand “C” view being a like image but with the actuator extended, and therefore showing substantially undeflected transmission of the beam through the intersection;  
         [0050]      FIG. 3  is a set of two elevational cross-sections, copied from the above-mentioned &#39;435 patent and its precursor applications, of a waveguide assembly according to preferred embodiments of the invention—the left-hand or “A” view showing the actuator extended, and the right-hand “B” view showing it contracted and retracted;  
         [0051]      FIG. 4  is a set of three cross-sectional views, all somewhat schematic or diagrammatic, of a first embodiment that is formed with one or more flappers, for directional flow control, and having a pair of actuator chambers with respectively associated pairs of wells and flappers, each chamber and well being generally analogous to the  FIG. 3  single chamber and well—here the topmost or “A” view being in plan, taken along the line  4 A- 4 A in the central or “B” view; and the central and lower, or “B” and “C”, views being taken along the line  4 B- 4 B in the “A” view; and the “B” and “C” views showing the actuator retracted and extended respectively;  
         [0052]      FIG. 5  is a set of three views, generally like those of  FIG. 4  but of a second embodiment with flappers, and here having a single actuator chamber but a pair of wells—and with the “A” view being taken along the line  5 A- 5 A of the “B” view, while the “B” and “C” views are taken along the line  5 B- 5 B of the “A” view;  
         [0053]      FIG. 6  is another three-view set, but of a third flapper embodiment, here having not only a single chamber but also a single flapper—and with the “A” view being taken along the line  6 A- 6 A of the “B” view, while the “B” and “C” views are taken along the line  6 B- 6 B of the “A” view;  
         [0054]      FIG. 7  is a pair of diagrams, both highly schematic, that show exemplary preferred embodiments of the invention—the upper or “A” diagram representing a two- (sample and reference) fluorescence and/or polarization configuration of the invention; and the lower “B” diagram being two views of a chemistry/biology chip with a pump and waveguide system (the overall chip array  65  includes a representative portion  68 , seen in greater detail in an enlarged view  65   e,    68   e —which is “exploded” from the overall array  65  along lines  68 ′);  
         [0055]      FIG. 8  is a first of three system or block diagrams, also highly schematic, of a microfluidic pump and waveguide sensor system that can be either external or implanted (the term “implanted” here being used to encompass implantation in a device as well as in a living organism)—for chemical or biological agent identification and detection applications; this  FIG. 8  system being particularly intended for biological monitoring or dispensing, or both;  
         [0056]      FIG. 9  is a second of the three diagrams, of a pump-and-sensor system particularly intended for industrial monitoring or dispensing; and  
         [0057]      FIG. 10  is a third such diagram, of a system particularly intended for industrial dispensing. 
     
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0000]     A. Switching  
         [0058]     As a three-layer substrate sandwich structure or “switch fabric”  11  ( FIG. 1 ), the switch of preferred embodiments includes a waveguide in a substrate  14 , membrane substrate  15 , and actuator substrate  16 . Central to the operation of this switch is the actuator  15 - 16 , used to fill and empty the columns, and the expanded gas  25  and pressurized gas  26  as shown.  
         [0059]     The switch works by moving the sample fluid located in the columns by a distance  32  that can be called “ΔX”. It is this actuation aspect that serves as the pumping mechanism, and reciprocation is caused by changes in relative pressure within the multiple chambers.  
         [0060]     With the actuator relaxed, gas  25  is present at the waveguide channel interface  21  (left-hand views). Total internal reflection results at that point  21 , and the entering light  17  is there deflected ninety degrees to leave the crossing waveguide  22 .  
         [0061]     With the actuator extended, gas  26  at the top of the column is compressed—inserting index-matched fluid into the waveguide-channel interface  23 . Internal reflection no longer occurs, and the entering light  17  is instead transmitted substantially straight through the interface to instead exit from the direct extension  24  of the entry waveguide.  
         [0062]     The microfluidic pump system of this invention thus takes advantage of the incompressibility of the index matching fluid and the ratios of the column-to-reservoir cross-sectional areas. An actuator extends Δx, displacing fluid up the column ΔX to complete the light circuit—with the fluid allowing light to continue traveling through the waveguide in one direction or the other as detailed above.  
         [0063]     ΔX/Δx ratios of greater than 1000:1 are possible, based on the column and reservoir cross-sectional areas envisioned. The total internal reflection (TIR) is represented by a column of triangular cross-section located at the intersection of each input and output optical channel in the waveguide substrate.  
         [0064]     When a switched state is desired, the actuator is retracted by Δx and the pressurized gas  26  returns the column to its original location. With a lower-index gas at the waveguide interface, as noted earlier total internal reflection occurs at the column-waveguide interface and the incoming light is switched 90°. Switch speed is dependent on the time it taken to move the column ΔX.  
         [0065]     A 250:1-scale acrylic/polycarbonate prototype A ( FIG. 2 ) of a single actuator/fluid column junction with 500:1 stroke amplification has been demonstrated to verify the concept. Actual deflection B and direct transmission C were observed and recorded.  
         [0000]     B. Pumping—Basic Forms  
         [0066]     The concept of the microfluidic pump system of this invention incorporated into a chem/bio chip utilizes the same elements as the optical switch in a micropump configuration, for moving the fluid  42  ( FIG. 3 ) into a sensor field of view. An advantage provided by this pump configuration is that the fluid-velocity ratios are proportional to the column-to-reservoir ratio of cross-sectional areas.  
         [0067]     An actuator  45  extends its membrane  44  at a rate Δx/Δt, displacing fluid  41  up and out of the column  46  toward the waveguide  43 , at a greater rate ΔX/Δt—thus expelling the initially present agent  41  from the optical-interaction region of the column. The actuator then completes the light circuit with fluid  42 , drawn into the interaction region, while allowing light to continue traveling through the waveguide  43 .  
         [0068]     The ratio of the individual ratios ΔX/Δt/Δx/Δt can exceed 1000:1, based on the column and reservoir cross-sectional areas envisioned. In this preferred embodiment, the top of the column is open to the external environment.  
         [0069]     In this configuration the microfluidic pump system is used as a displacement pump, expelling and drawing the agents of interest into the waveguide interaction region as just described. Center-to-center distances for each sample site can be on the order of 100 to 200 μm, with displacement frequencies in excess of 1 MHZ.  
         [0070]     The resulting volumetric transfer rate is on the order of 10 −5  L/sec (ten microliters per second). The power consumption is 200 mW at 5 V.  
         [0071]     Multiple detection configurations are envisioned utilizing the microfluidic-pump systems of this invention. Detection approaches that can utilize the microfluidic pump and planar waveguide of any embodiments of the invention include, but are not limited to: 
        fluorescence,     polarization,     refractive-index variation,     acoustooptic tunable filters,     Fabry-Perot interferometry, and     “μ-scale” grating spectrometry.        
 
         [0078]     The microfluidic pump system of the invention in combination with the waveguide can detect both chemical and biological agents in liquids or in gases. Examples of such detection applications include but are not limited to blood or other bodily fluid monitoring, use as a chemical sensor for process control, leak detection or safety monitoring; or use as a biological sensor for use in detecting and monitoring toxins.  
         [0079]     Other examples described below include monitoring a heating/ventilation and/or air-conditioning system, monitoring a fuel-injection system, monitoring a chemical processing system, or triggering an alarm.  
         [0080]     The microfluidic pump system, alone, can be used in pump applications such as dispensing drugs, externally or as an implant, as an assay dispenser, as a means of moving liquids and gases within the field of view of a detection system, or even to assist a heart pump, or other similar applications.  
         [0081]     As will be seen from certain of the embodiments discussed below, the reciprocating microfluidic pump system of the invention may sometimes perhaps be more accurately described as a “recirculating” microfluidic pump system. Some embodiments of the invention can be used not only in embodiments that include a waveguide, but also in combination with a nonreciprocating microfluidic pump.  
         [0000]     C. Pumping—Plural-Duct Forms  
         [0082]     One preferred embodiment of the invention is configured as a reciprocating microfluidic pump that has two chambers  447   a,    447   b  ( FIG. 4 ). These chambers in turn have associated columns or ducts  446   a,    446   b  respectively, linked by an interconnecting tunnel  449 .  
         [0083]     The chambers also have actuators  445   a,    445   b  that contract and expand in tandem. Both actuators, connected to the membranes or diaphragms  444   a,    444   b  in their respective chambers  447   a,    447   b,  contract during an intake or “ingestion” phase ( FIG. 4B ). The resulting increases in the chamber volumes draw fluid into the first chamber  447   a.    
         [0084]     A flapper valve  448   a,  cantilevered perpendicular to the intake column  446   a,  is pulled toward the actuator by the fluid flow downward in that column—thus diverting fluid from that column  446   a  into the linking tunnel  449 . A second flapper  448   b,  covering the second column  446   b,  prevents fluid from entering the second chamber  447   b  via the top of that second column. The flapper positions result in a net positive pressure difference between the chambers  447   a,    447   b.    
         [0085]     During an expulsion phase ( FIG. 4C ), the actuators  445   a,    445   b  expand, reducing the chamber volumes. The flappers of both chambers are pushed away from the actuators due to fluid motion. The flapper  448   a  at the first chamber  447   a  diverts fluid from that chamber toward the second chamber  447   b,  through the linking tunnel  449 , with a net flow of fluid out of that second chamber.  
         [0086]     Consequently the flow through the two chambers and passageways is in the same direction during both phases (actuator contraction and expansion) of the system. The overall result of each reciprocation of the actuators  445   a,    445   b  is therefore to pump fluid in through the first column  446   a,  thus functioning as an intake port, and out through the second column  446   b  as an exhaust port.  
         [0087]     In addition to providing a pump for sensor technology, the reciprocating microfluidic pump system of this invention can be used to dispense medicines in small doses as an implant in the body. In an alternate configuration (not shown) the flapper over the second column is eliminated, and the flapper at the first column continues to provide an appropriate flow resistance, producing a net circulation into the first column  446   a  and out of the second column  446   b.    
         [0088]     Other configurations similar to this, with one or more chambers and two or more columns, are also possible. Thus another preferred embodiment utilizes only a single chamber  547  ( FIG. 5 )—but with an analogous network of three ducts  546   a,    549 ,  546   b.    
         [0089]     In this configuration, the flappers  548   a  and  548   b  at the two columns  546   a,    546   b  operate just as the flappers discussed above. When the single actuator  545  contracts ( FIG. 5B ), the chamber volume increases and fluid flows into the first column  546   a,  through the linking tunnel  549  and down the second column  546   b  into the chamber  547 .  
         [0090]     The flapper valve  548   b  over the second column  546   b  is closed. The flapper  548   a  perpendicular to the first column  546   a  is displaced by the flow through that column  546   a  and the linking tunnel  549 , allowing flow into the chamber  547  due to the relative pressure.  
         [0091]     When the actuator expands ( FIG. 5C ), the volume of the one chamber decreases and the flapper at the top of the second column  546   b  opens—allowing flow out of that column—and the flapper inside the second column  546   a  is displaced but prevents flow out of column  1 .  
         [0092]     This cycle continues indefinitely, resulting in a reciprocating pumping action very generally as before. Since only one chamber is in use, this system moves only a fraction as much fluid as the two-chamber embodiment ( FIG. 4 ) discussed above.  
         [0093]     Yet another preferred embodiment has a single chamber  647  ( FIG. 6 ), as in the embodiment just discussed, but with one of the flappers located at the intersection between the linking tunnel  649  and the second column  646   b.  When the actuator  645  contracts ( FIG. 6B ), the chamber volume increases—and intake fluid flows into the first column  646   a,  thence through the linking tunnel  649 , and finally down the second column  646   b  into the chamber  647 .  
         [0094]     The flapper  648   b  over that second column  646   b  is closed, and another flapper  648   a—just at the intersection between the linking tunnel  649  and the second column  646     b —is open. That intersection flapper thus allows flow into the chamber due to the relative pressure.  
         [0095]     When the actuator expands ( FIG. 6C ), the volume of the chamber decreases and the flapper  648   b  at the top of the second column  646   b  opens, allowing exhaust flow out of that column. Meanwhile the flapper  648   a  at the tunnel intersection  649 - 646   b  closes, preventing backflow through the linking tunnel  649 .  
         [0096]     This cycle continues indefinitely, resulting in a reciprocating pumping action. Like that in the embodiment discussed just previously ( FIG. 5 ), the pump is unidirectional but operates at lower flow than the two-column embodiment discussed first ( FIG. 4 ).  
         [0000]     D. Detection  
         [0097]     In one preferred configuration for a detection method, a laser source  17  ( FIG. 7A ) is used to detect either fluorescence or polarization characteristics of a particular agent. The source radiation propagates through an initial segment of waveguide, preferably to a beam-splitter  59  where the radiation is divided into two paths.  
         [0098]     From the splitter  59 , some of the radiation continues through a reference-channel waveguide to interact with the agent, e. g. sample chemical. The agent is positioned in a preferably open sample column  56 , by a micropump according to other aspects of the invention.  
         [0099]     Radiation remaining after traversal of the sample column  56  continues along the waveguide to a sample-channel detector  52 . This detector generates an output sample signal, usually electronic.  
         [0100]     Radiation not directed by the beam-splitter  59  to the sample column  56  proceeds instead along a reference channel, within the waveguide, to a capped reference column  56   r.  Radiation remaining after traversal of the reference column  56   r  continues along the reference channel to a reference-channel detector  52   r,  which generates an output reference signal.  
         [0101]     In this system, changes due to the agent can be detected on a fractional basis, by monitoring the ratio of the sample-detector  52  output to the reference-detector  52   r  output. In other words the photon signal coming from the sample channel  56 ,  52  is normalized to the total amount of energy initially present at the λ source  17 —as represented by the signal from the reference channel  56   r,    52   r.    
         [0102]     All of these configurations can work with the chamber membrane displaced to increase or decrease chamber volume, by configuring the actuator to expand, increasing volume, and contract, decreasing volume. Furthermore, either used alone or combined with a waveguide for detection purposes, the microfluidic pump system of the invention is advantageously further combined with a computer or an integrated processor to automate its monitoring capabilities and responses.  
         [0103]     The radiant-energy source (e. g. laser or photodiode), detection method and/or processor may each be integrated into a chem/bio chip  65  ( FIG. 7B ) along with the microfluidic pump system itself. The overall chip array  65  includes a representative portion  68 ,  68   e.    
         [0104]     Substantially each region  65   e  of the chip  65  includes numerous waveguide-input and -output optical channels  67 ,  62  respectively. Sampling columns and pumps  66  are disposed along the guides  67 ,  62 .  
         [0105]     This arrangement is especially advantageous for applications in which the entire pump/waveguide system is for implantation in a living body, or within a closed assay system.  
         [0106]     The guides  67 ,  62  can be spaced at 50 μm on centers, or even less. The openings of the chambers  66  can be 10 μm by 10 μm and less. Thus over 20,000 sites are possible on a chip that is 10 mm square.  
         [0000]     E. Detection and Distribution  
         [0107]     The previously discussed pump/optical-waveguide detection device  840  ( FIG. 8 ) can be used together with a reciprocating microfluidic pump device  846   a′,    846   b′  as part of a larger system for detection of chemical or biological agents, or both. In such a system, both of the micropump devices are integrated into respective chem/bio chips.  
         [0108]     One or more such chips advantageously are still further integrated into a single chip. If desired, such an integrated system can also include one or more detectors  852 ,  852   r,  processing capability  873 ,  873   a,  and one or more radiation sources  17  and reservoirs  871 ′ for the agent material. Such a chip advantageously also includes access points  841 ′,  842  to one or more bodily organ or a body&#39;s circulatory system  871 .  
         [0109]     The overall system, or portions of it, are readily implanted in the body or within a closed assay system, or can be used externally. A sample fluid or gas  842  from an organ  871 —for example the stomach or the circulatory system—enters the open column of the microfluidic pump  840 . These specimen fluids or gases are drawn into the interaction region of the column, which contains the optical-waveguide sensor  867 ,  862 .  
         [0110]     Such specimens may be, e. g., bodily secretions such as blood, urine, semen or saliva. Alternatively specimens monitored or pumped in this embodiment—or other embodiments discussed in this document—may be air, water, or any number of industrial or environmental test samples such as exhaust, fuel or lubricant.  
         [0111]     Any of these systems may use additional means to direct sample medium to the monitoring column(s). For greater exposure to the sample medium, the system itself may simply be located on a structural support (e. g. located in or on a wall or passageway).  
         [0112]     A source  17  of radiant energy e. g. light is aligned with the waveguide inlet  867 , which passes the energy to the column containing the specimen. The radiant-energy source  17  may be a simple visible-light source, or other types as indicated in this document or the documents incorporated by reference. (After monitoring, the specimen in the column simply becomes sampling exhaust  941 .) Whatever fraction of the energy passes through the specimen in the column, augmented by any fluorescence energy produced by the specimen, continues through the waveguide outlet  862 , which then emits an optical signal.  
         [0113]     That resulting signal proceeds along an optical fiber or other guide  868  to a detector  852 , which may also have an associated reference channel  852   r.  Various detection methods, listed earlier, may be used to interpret this optical signal.  
         [0114]     For the sake of simplicity the “Detector” block  852 ,  852   r  will here be understood to include all such interpretive components, yielding an electrical or other data flow  872 . This latter information sequence is then advantageously directed for processing to a separate computer  873 , or alternatively to a microprocessor  873   a  that is integrated within the bio/chem chip itself.  
         [0115]     The computer or integrated processor can thus monitor the sample and can automate a response by relaying information  870  to another mechanism such as an alarm  874 . The response can also be formulated as a signal  871 ″ for control of the reciprocating microfluidic pump, to cause it to appropriately respond based on the resulting data.  
         [0116]     The reciprocating microfluidic pump may respond by pumping and thereby expelling drugs or other agents  842 ′ from a reservoir  871 ′ along a return path  841 ′ to the organ etc.  871  that is being monitored. The pump instead may discontinue expelling such agents, depending on which is the appropriate response to the computer- or processor-developed command  871 ″.  
         [0117]     Applications of the invention are not limited to monitoring and dosing of a living organism. Thus for instance an industrial process stream, or combustion engine, or environmental sampling system (not shown) can produce a specimen  971  ( FIG. 9 ). Thus the specimen may be, e. g., air, water, exhaust, or fuel lubricant.  
         [0118]     This specimen  971  here too proceeds  942  into a system consisting of—in combination—a pump/optical-waveguide detection device  940  together with a reciprocating microfluidic pump device  946   a′,    946   b′.  The specimen flow  942  is directed to the column  946  of an optical pump/detection module  940 , as before.  
         [0119]     The elements  941 ,  946 ,  962 ,  967 ,  968 ,  952 ,  952   r  correspond to the previously discussed elements similarly numbered but with prefix “ 8 ” instead of “ 9 ” ( FIG. 8 ). The radiation source  17  is typically the same here as in other embodiments.  
         [0120]     The detector  952 , including optional reference channel  952   r  and any associated interpretive modules, produces data  972 ′ that proceed to a separate computer  973 . As before an alternative special-purpose processor  973   a  may instead be integrated into the substrates of the invention.  
         [0121]     Processor output-data or control signals  970  flow to an alarm or access module  974 , or for example to a heating/ventilating/air-conditioning (“HVAC”) system  975 . The data or control signals  970  can instead control a chemical-processing module  976 , or a fuel-injection module  979 ; in these latter cases actual physical chemical or fuel flows  971 ″ proceed to become inputs  942 ′ to the pump unit  946   a ′,  946   b′.  The appropriate automated monitoring response in all of these embodiments depends on the application or goal of the system and its connected components.  
         [0122]     The HVAC automated monitoring response may be as simple as turning on or off vents or circulating fans without the need for turning on a reciprocating micropump. On the other hand, an automated fuel injection system response may require a reciprocating micropump to draw minute amounts of fuel  979  from a reservoir  971 ′ and pump it into an engine or other reaction vessel  981  in a controlled fashion.  
         [0123]     (This part of the system is illustrated only very diagrammatically, as the paths  976 ,  979 ,  971 ″ may represent either [a] fluid flows entering the pump  946   a ′,  946   b ′ or [b] control signals to operate the pump  946   a ′,  946   b ′.)  
         [0124]     Likewise, automated monitoring of a chemical processing system may require a reciprocating micropump to draw distinct amounts of chemical or biological agents from a reservoir and pump them into a reaction vessel. The appropriate automated monitoring response in these examples depends on the application or goal of the system and its connected components.  
         [0125]     The pump unit may receive at  942 ′, instead of fuel or other chemicals from the computer-controlled modules  979 ,  976 , separate quantities of agent from a reservoir  971 ′. In either case the pump ejects the pumped fluid  941 ′ to a reaction vessel  981  for further physical processing, and/or back as process-control samples  941 ′ to the monitoring-stage input flow  942 .  
         [0126]     The reciprocating microfluidic pump system can be used for a variety of applications that require pumping of distinct and minute amounts of liquids or gases. The invention is not limited to these examples.  
         [0127]     As yet another group of examples, the reciprocating microfluidic pump  1046   a,    1046   b  ( FIG. 10 ) can be used simply as a delivery system, without necessarily any provision for monitoring. Here the pump draws in gas or liquid  1042  such as printer ink from a reservoir  1071  and expels the agent at  1041  in a discrete and controlled manner for applications such as an intravenous (“IV”) drip  1086 , a microassay sample slide  1085 , a fuel injector system  1079 , chemical processing system  1076 , or even a printer  1084  (in the case of printer ink).  
         [0128]     Certain preferred embodiments of the invention have been commercialized under the trade name “LightLinks”—which is a trademark for a proprietary system of Areté Associates. Some forms of that system include a microfluidic pump, diaphragm membrane, waveguide-based optical interconnecting channel, and actuator substrate.  
         [0129]     The foregoing disclosures are merely exemplary of the present invention, whose scope is to be determined by reference to the appended claims.