Abstract:
Component microfluidic devices which are integrated with polydimethylsiloxane (PDMS) microfluidic chips, include designs for an electrical and optical pressure gauge, valve, electrostatic and magnetic pumps, alternating or mixing pumps, a solenoid, a magnetometer, a magnetically actuated reversible filter and valve, and a hydrolysis valve. These devices enhance and miniaturize microfluidic control, thereby expanding the available capabilities and allowing complete system miniaturization for handheld diagnostic apparatuses.

Description:
RELATED APPLICATIONS 
     The present application is related to U.S. Provisional Patent Application Ser. No. 60/721,364, filed on Sep. 28, 2005, U.S. Provisional Patent Application Ser. No. 60/729,674, filed on Oct. 24, 2005 and U.S. Provisional Patent Application Ser. No. 60/756,703, filed on Jan. 6, 2006, all three of which are incorporated herein by reference and to which priority is claimed pursuant to 35 USC 119. 
    
    
     GOVERNMENT SUPPORT 
     The invention was developed in part using funds provided by the U.S. Government under an NIH contract no. 1RO1 HG002644-01A1. The U.S. Government has certain rights. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The invention relates to the field of microfluidic devices and in particular to microfluidic pumps, pressure gauges and other components and to their method of operation. 
     2. Description of the Prior Art 
     Microfluidics is an exciting new technology that is establishing itself as an innovative practical tool in biological and biomedical research. Microfluidics offers the advantages of economy of reagents, small sample handling, portability, and speed. PDMS (polydimethylsiloxane) microfluidics in particular offers industrial scalability, parallel fabrication, and a unique capability for complex fluid handling schemes through fluidic networks containing integrated valves and pumps. However, microvalve actuation is still based on pneumatic control by macrovalves external to the devices themselves, while signal detection is generally done by optical microscopy, or some other macro means. By comparison to microfluidic technology itself, integration of electrical and optical devices into PDMS microfluidic chips is only at the dawn of its development. Herein lies an opportunity to produce a series of important devices for fluidic manipulation and signal detection. 
     The past ten years have witnessed the rapid development of PDMS (polydimethylsiloxane) microfluidic technology from the simplest of channels to an extended family of devices integrated by the thousands within the same chip. Such chips have emerged as the micro-scale hydraulic elastomeric embodiment of Richard Feynman&#39;s dreams of infinitesimal machines. PDMS microfluidics has been driven by applications from the beginning, with every advance being rapidly employed in devising solutions to specific problems. Thus it is no surprise that many exciting specialized chips have emerged to offer new capabilities, e.g. in protein crystallization, DNA sequencing, nanoliter PCR, cell sorting and cytometry, nucleic acids extraction and purification, immunoassays, and cell studies. After the development of pure microfluidic technology and the subsequent vigorous pursuit of its biological applications, it is becoming clear that the next generation of microfluidic devices would combine the fundamental technology with integrated electrical and/or optical systems for control and measurement. Such integration offers new analytical and functional capabilities, as well as true overall device miniaturization. A few steps in this new direction have already been taken, producing a capacitance cytometer, thermal cycler, and a spectrophotometer. Moreover, such devices can be arranged as independent but interconnected modules functioning within the boundaries of a single chip. Such chips with specific emphasis on devices for medical applications are called nanomedicine chips. They are anticipated to have the plumbing, electronics, temperature control, and functional capabilities to allow significant miniaturization of many of the current clinical laboratory machines. 
     BRIEF SUMMARY OF THE INVENTION 
     What is disclosed are designs for electromagnetic microdevices which are integrated with polydimethylsiloxane (PDMS) microfluidic chips, including valves, pumps, a magnetometer, and a filter. These devices enhance and miniaturize microfluidic control, thereby expanding the available capabilities and allowing complete system miniaturization for handheld diagnostic apparatuses. 
     The invention in one embodiment is thus a microfluidic apparatus for measuring pressure comprising a plurality of fluidic microvalves, a control channel for admitting a pressure to be measured communicated to the plurality of fluidic microvalves, and a plurality of flow channels corresponding to the plurality of fluidic microvalves. Each of the plurality of fluidic microvalves is characterized by a different closing/opening pressure. It must be understood that the fluidic microvalves can be of any design now known or later devised, including push-down or pull-up membrane valves, and it may be either normally open or normally closed. A plurality of transducers is provided corresponding to the plurality of flow channels to measure a parameter of the corresponding flow channel indicative of valve closure status from which the pressure can be determined within a magnitude interval. 
     The plurality of transducers comprises an electrical transducer for measuring an electrical parameter of each corresponding flow channel or an optical transducer for measuring an optical parameter of each corresponding flow channel. Electrical and optical transducers do not exhaust the possibilities and any transducer type which can be employed in a fluidic circuit can be equivalently substituted. 
     The electrical transducer comprises a pair of electrodes communicated with the corresponding flow channel to measure electrical resistance or conductance in the flow channel through the corresponding microvalve. An electronic circuit is coupled to the electrodes to provide the necessary electrical measurement of resistance or conductance or such other electrical parameter which may be equivalently chosen. 
     In one embodiment each of the plurality of fluidic microvalves has a membrane as the active element in the valve, and the membrane and valve is characterized by a different closing/opening pressure by means of different values for a membrane parameter. The membrane parameter includes, but is not limited to, the area of the membrane, a thickness of the membrane, or Young&#39;s modulus of the membrane. Again these choices with respect to membrane parameters do not exhaust the possibilities of equivalents and any design feature of the membrane of its affixation in the valve which affects the opening and/or closing threshold pressures is deemed to be equivalent. 
     The invention is also characterized as a microfluidic apparatus for alternating pumping comprising a plurality of fluidic microvalves, a control channel for admitting a pressure to be measured communicated to the plurality of fluidic microvalves, and a flow channel communicated to the plurality of fluidic microvalves. Each of the plurality of fluidic microvalves is characterized by a different closing/opening pressure and is arranged in sequential communication with the flow channel in a monotonic order of closing/opening pressures, so that a changing pressure applied to the control channel causes sequential closing/opening of the plurality of valves to pump fluid within the flow channel back and forth, in alternating motion or mixing. 
     The invention is still further defined as a microfluidic apparatus for pumping comprising a plurality of electrode pairs, and a flow channel into which the plurality of electrode pairs are electrically communicated. The plurality of electrode pairs are arranged along a length of the flow channel in a sequential order to apply a selected sequence of electrostatic fields to fluid within the flow channel to move the fluid in a predetermined direction in the flow channel. Each of the plurality of electrode pairs define a space between the electrodes within the flow channel. The electrode pairs are interleaved so that the corresponding space between one electrode pair partially overlaps the corresponding space between an adjacent electrode pair. The apparatus further comprises a circuit for applying a selective voltage sequence to selected ones of the plurality of electrode pairs. 
     The invention contemplates a microfluidic apparatus for providing a solenoidal magnetic field comprising a substrate, a current-carrying microchannel defined in the substrate, and a flow microchannel defined in the substrate. The current-carrying and flow microchannel are intertwined with each other. A conductive material is disposed in the current-carrying microchannel so that when current is applied thereto, the solenoidal magnetic field is created in which the flow microchannel is disposed. In the illustrated embodiment the conductive material is disposed in the current-carrying microchannel comprises electroplated metal filling the current-carrying microchannel. 
     Again in the illustrated embodiment the flow microchannel is substantially straight and the current-carrying microchannel is fabricated so that the current-carrying microchannel is coiled around the flow microchannel. In such a configuration or one equivalent to it, the apparatus is called a solenoidal microfluidic valve. 
     The invention is further characterized as a microfluidic apparatus for pumping comprising a plurality of microfluidic solenoids, and a flow channel disposed through the plurality of solenoids. The plurality of solenoids are arranged along a length of the flow channel in a sequential order and spaced apart to apply a selected sequence of magnetic field packets to a magnetically entrained fluid within the flow channel to move the fluid in a predetermined direction in the flow channel. The magnetically entrained fluid is comprises of a fluid with magnetic particles or nanobeads entrained therein. 
     The apparatus further comprises a circuit for selectively applying current to the plurality of microfluidic solenoids in a sequential order to move the fluid in the predetermined direction in the flow channel. 
     The invention is also rendered as a reversible microfluidic apparatus for filtration or valving comprising a microfluidic solenoid, and a flow channel disposed through the solenoid, and a plurality of magnetic particles entrained in a fluid within the flow channel, so that energization of the solenoid temporarily compacts the magnetic particles within a predetermined location in the flow channel within the solenoid to substantially reduce or stop flow of fluid through the flow channel or to filter flow of fluid through the flow channel. 
     The apparatus further comprises an ammeter coupled to the conductive material disposed in the current-carrying channel to measure the current resulting from EMF induced by the change of magnetic field as magnetic material approaches and passes through the flow channel. 
     The invention is yet further defined as a microfluidic apparatus for valving comprising a control channel, a flow channel corresponding to the control channel, a fluidic microvalve communicated to the control channel and pneumatically controlled therethrough to selectively open or close the flow channel, and an hydrolysis chamber wherein a liquid is selectively hydrolyzed to a gaseous state to activate the microvalve, the hydrolysis chamber being communicated to the control channel. In this embodiment the resulting apparatus is called a microfluidic hydrolysis microvalve. 
     The invention can also be characterized as a microfluidic apparatus for pumping comprising a plurality of microfluidic hydrolysis microvalves, a control channel communicated to the plurality of microfluidic hydrolysis microvalves, and a flow channel, where the plurality of microfluidic hydrolysis microvalves are sequentially communicated along the flow channel, so that when the plurality of microfluidic hydrolysis microvalves are selectively operated in sequence fluid is moved along the flow channel in a predetermined direction. 
     In general the invention includes a microfluidic apparatus for pumping comprising a flow channel, a plurality of microfluidic means for affecting flow in the flow channel, and a control channel communicated to the plurality of microfluidic means. Each of the plurality of microfluidic means is sequentially communicated along the flow channel, so that when the plurality of microfluidic means is operated in a selected sequence, fluid is moved along the flow channel in a predetermined direction. 
     In the illustrated embodiments the plurality of microfluidic means comprises a selectively operated electrostatic valve, a selectively operated microfluidic solenoid, one of a sequence of selectively operated microfluidic valves with an unique opening/closing pressure chosen from a monotonic sequence of magnitudes, or combinations of the same. 
     Still further the invention includes methods of operation for each of the foregoing described microfluidic apparatus. 
     While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 USC 140, are not to be construed as necessarily limited in any way by the construction of “means” or “steps” limitations, but are to be accorded the full scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents, and in the case where the claims are expressly formulated under 35 USC 140 are to be accorded full statutory equivalents under 35 USC 140. The invention can be better visualized by turning now to the following drawings wherein like elements are referenced by like numerals. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1   a - 1   f  are schematic diagrams illustrating the structure and operation of a peristaltic pump according to the invention. 
         FIGS. 2   a - 2   c  are schematic diagrams illustrating the structure and operation of a microsolenoid according to the invention. 
         FIGS. 3   a - 3   d  are schematic diagrams illustrating the structure and operation of a plurality of microsolenoid stages acting as a pump according to the invention. 
         FIGS. 4   a - 4   d  are schematic diagrams illustrating the structure and operation of a plurality of valves operating as a pressure gauge according to the invention. 
         FIGS. 5   a  and  5   b  are schematic diagrams illustrating the structure and operation of a plurality of valves operating as a pressure gauge with electrical readout according to the invention. 
         FIGS. 6   a  and  6   b  are schematic diagrams illustrating the structure and operation of a plurality of valves operating as a pressure gauge with optical readout according to the invention. 
         FIGS. 7   a  and  7   b  are schematic diagrams illustrating the structure and operation of a plurality of valves operating as an alternating pump according to the invention. 
         FIG. 8  is a photograph of a microfluidic array used to test the operability of the invention as a pressure gauge. 
         FIG. 9   a  is a graph of the closing pressures of the valves of  FIG. 8  as a function of valve length. 
         FIG. 9   b  is a graph of the electrical resistance of the flow channel through the valves of  FIG. 8  as a function of pressure. 
         FIG. 10  is a diagram of an electrolysis microvalve. 
     
    
    
     The invention and its various embodiments can now be better understood by turning to the following detailed description of the preferred embodiments which are presented as illustrated examples of the invention defined in the claims. It is expressly understood that the invention as defined by the claims may be broader than the illustrated embodiments described below. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Electrical-Microfluidic Pressure Sensor Alternating Pump 
     The disclosed pressure gauge is one of a set of components that will become increasingly important as microfluidics was developed further into hybrid integrated architectures wherein microfluidic and electrical components were combined to form advanced novel devices. In particular, this sensor can be used to monitor pressure and electrically report the result to the logic circuitry that controls the overall PDMS MEMS device. The first electrical-microfluidic pressure sensor is thus disclosed here. Applied pressure determines the status of an array of PDMS microfluidic valves  36  of varying closing pressures. The electrical resistance of each valved channel  40  was high if and only if the respective valve  36  was closed. Thus valve array status and, therefore, an interval estimate of the pressure, were reported electrically. The overall microdevice functions as a pressure gauge with electrical readout. Its compatibility with both electrical circuitry and the basic PDMS microfluidic technology make it a suitable subsystem for the next generation of hybrid PDMS MEMS. 
     A pressure gauge  30  for soft-lithography PDMS microfluidics is disclosed as illustrated in  FIGS. 4   a - 4   b ,  5   a ,  5   b ,  6   a  and  6   b  and an alternating pump  32  as illustrated in  FIGS. 7   a  and  7   b . The pressure gauge  30  reads the value of the applied pressure using the property that different valve dimensions result in different closing pressures in a heterogeneous valve array. In addition, this readout is convertible to an electrical or optical signal, e.g. by conductance/capacitance or waveguide light intensity measurements respectively. An alternating pump  32  moves flow channel  40  fluid back and forth with zero net displacement over one cycle, thereby enabling mixing in a straight channel  40  and facilitating reactions between the liquid phase and the microchannel surface  34 . Both devices  30  and  32  are built using already available soft-lithography fabrication techniques and are fully compatible with already known device components. 
     An electrolyte-filled valved microchannel  40  in a PDMS chip experiences a drastic increase in electrical resistance when and only when it is completely pinched off by the microvalve  36 . This effect establishes a 1-1 correspondence between electrical resistance (low or high) and valve status (open or closed), thereby providing an electrical means of reporting valve status. Valve status (open or closed) is determined by applied pressure being below or above the characteristic closing pressure of the valve  36 ; therefore, the valve  36  reports an upper or lower bound for the applied pressure, respectively. An array of such valves  36  of varying closing pressures reports a set of inequalities that produce an interval estimate for the pressure. That estimate is reported as a set of resistance values of the respective microchannels, due to the 1-1 correspondence above. Hence, the overall system acts as an electrical microfluidic pressure gauge. This sensor forms a useful subunit within PDMS MEMS (micro-electro-mechanical systems), e.g. by reporting pressure values to electrical feedback control loops. 
     What is disclosed is the first known electrical microfluidic pressure gauge  30 . Each valve  36  remains open up to some characteristic pressure determined by its dimensions. Therefore, there is another 1-1 correspondence, this time between valve status (open/closed) and applied pressure (below/above the valve&#39;s characteristic pressure). In essence, valve status is equivalent to an upper or lower bound on the applied pressure. Then, an array of valves  36  closing at different characteristic pressures would offer a set of inequalities that combine to produce an interval estimate of the applied pressure. The 1-1 correspondence between valve status and electrical resistance allows reporting this estimate electrically as a set of resistance states of the respective microchannels  40 . The resulting system acts as a microfluidic pressure gauge with electrical readout. The device compatibility with standard PDMS microfluidic technology and electrical control make it ideally suitable for integration in the future PDMS MEMS. 
     Morphologically, a pressure gauge  30  is a heterogeneous array of interconnected valves  36  that control one or more flow channels  40  as described in  FIGS. 4   a - 4   d . As is conventionally known different physical dimensions of the microfluidic valve membranes result in different closing pressures whether they be push-up or pull-down valves  36 . An array of microfluidic valves  36   a - 36   c  of varying membrane dimensions indicate the applied pressure by the open/shut state of the valves  36   a - 36   c  as depicted diagrammatically in the example of  FIGS. 4   a - 4   d . A control channel  38  is communicated to each valve  36   a - 36   c  and each valve  36   a - 36   c  controls flow channel  40  or a separate corresponding flow channel  40 . For example, valve  36   a  closes only at a predetermined minimum pressure P 1 &gt;P atm  as determined by its membrane size as indicated in  FIG. 4   b . Valve  36   b  closes only at a predetermined higher minimum pressure P 2 &gt;P 1  as determined by its membrane size as indicated in  FIG. 4   c . Valve  36   c  in turn closes only at a predetermined higher minimum pressure P 3 &gt;P 2  as determined by its membrane size as indicated in  FIG. 4   d . The sensed pressure is thus measured or binned according to these predetermined pressures P 1 -P 3 . If the measure pressured P&lt;P 1 , then all valves  36   a - 36   c  are open. If the measured pressure P 1 &lt;P&lt;P 2 , then valve  36   a  is closed and valves  36   b  and  36   c  are open. If the measure pressure P 2 &lt;P&lt;P 3 , then valves  36   a  and  36   b  are closed and valve  36   c  is open. If P&gt;P 3  then all valves  36   a - 36   c  are closed. The precision of pressure measurement is increased by increasing the number of valves  36  and their closeness of their membrane areas. 
     If the dimensions are properly chosen, the result can be a calibrated pressure scale, which may be arranged to be linear. The readout is then converted into an electrical, optical signal or other signal for transmission and processing. For example, if electrical contacts  42  are fabricated in the microfluidic substrate of the corresponding flow channels  40   a - 40   c , both the measured capacitance and conductivity changes in channels  40   a - 40   c  change when the respective valve  36   a - 36   c  switches state as shown in  FIGS. 5   a  and  5   b.    
     Alternatively, if the flow channels  40  are filled with a high refractive index substance, e.g. photoresist, and the channels  40   a - 40   c  are used as light waveguides, then a valve switching state changes the intensity of transmitted light as depicted in  FIGS. 6   a  and  6   b . The measured changes in both cases produce an upper and lower bound for the applied pressure. 
     It should be noted that a heterogeneity of closing pressures can be produced not only by varying the lateral dimensions of the valve  36  as shown in  FIGS. 4   a - 4   d , but also by varying other valve or membrane parameters, e.g. thickness of the membrane and Young&#39;s modulus of the polymer. No PDMS pressure-sensing device has previously been reported, which makes the described pressure gauge the first of its type. 
     Morphologically, an alternating pump  32  is a heterogeneous array of interconnected valves  36  arranged in either ascending or descending order of closing pressure from the pressure source along the flow channel  40  as diagrammatically depicted in  FIGS. 7   a  and  7   b . When pressure is applied, leakage into the valve pockets does not allow the static pressure to reach its maximal applied value immediately. As a result, the valve  36  of lowest closing pressure closes first, followed by the next valve  36  in ascending order of closing pressure, thereby producing a net displacement along the same direction as indicated in  FIG. 7   a . When pressure is released, static pressure drops and the valve  36  with the highest dosing pressure will snap open first, followed by the next highest. Hence, valves  36  open in opposite order, producing an equal net displacement in the opposite direction as indicated in  FIG. 7   b . Thus a complete pump cycle produces overall zero net displacement but the contents of the flow channel  40  has moved back and forth, ergo the device is called an alternating pump. Such an alternating capability allows mixing in straight channels  40  and facilitates reactions between molecular species in the liquid phase and on the microchannel surface. As mentioned above, the heterogeneity of closing pressures can be accomplished by multiple means, but the functionality will be the same. 
     The operation of the alternating pump  32  can be duplicated by two serpentine pumps. With opposite chirality, one serpentine over a circular channel, one triplet pump with an alternating sequence, or one triplet pump aver a circular channel. All these alternatives, however, require more real estate on the chip and more control channels  38  (at least two or three, instead of one). Thus the alternating pump  32  has its niche of efficient application. 
     The fabrication of an array of 30 pairs of electrodes for the pressure gauge device  30  will now be described. DWL66 direct mask writer (Heidelberg Instruments GmbH, 69406 Heidelberg, Germany) with a 20 mm head was used to write the respective pattern on a glass slide coated with 90 nm non-oxidized chrome and 530 nm Az1500 photoresist (Telic Co., Valencia, Calif. 91 355). The photoresist was developed for 20 sec in Microposit MF-322 (Rohm and Haas Electronic Materials) and the glass slide was washed with deionized water. The now-exposed areas of chrome were etched away for 3 min in CR-7 “chromium photomask etchant, surfactant added” (Cyantek Corp.). The sample was washed with deionized water, blown dry, and stored as is. Immediately before assembly to the PDMS slabs, the substrate was washed with acetone to remove the remaining protective photoresist, washed with ethanol, and blown dry. 
     Conventional fabrication and mold techniques was employed to produce the molds and PDMS devices. The latter were washed in ethanol and blown dry before being bound to the ready metallized glass substrate. The now assembled chips underwent a final bake in an 80° C. oven overnight. 
     The macrofluidic setup for verification of operability included an inverted 1×50 Olympus microscope, pressure regulators from AirTrol Components Inc (New Berlin, Wis. 53146)) and a digital pressure gauge from TIF instruments Inc (Miami, Fla. 331 50). 23-gauge steel tubes from New England Small Tube Corp. (Litchfield, N.H. 03052) were plugged into the chip&#39;s control channel ports. Their other ends were connected through TygonB tubing (Cole-Parmer, Vernon Hills, Ill. 60061) to Lee-valve arrays (Fluidigm Corp. South San Francisco, Calif. 94080) operated by LabView software on a PC computer. A Nikon stereoscope SMZ-2T was equipped with a Nikon CoolPix990 color camera. Resistance measurements were conducted with a multimeter MiniRangernaster from Extech Instruments. Basic scheme conventional multilayer soft lithography was used to fabricate PDMS microfluidic chips. A comb-like array of 100 μm-wide flow channels  40   a - 40   e  . . . in the lower layer was crossed with a single control channel  38  in the upper layer to produce an array of pushdown microfluidic valves  36  of varying length (55 to 200 pm). This PDMS two-layer device was then bound to a metallized glass substrate in such a way that each prong of the comb was aligned with its own pair of electrical contacts, thereby completing the chip fabrication as depicted in the photograph of  FIG. 8 . 
     A salty buffer (Tris 10 mM, NaCl 10 mM, MgCl 2  0.1M, pH 8) was introduced in the lower (flow) channel  40  communicated with flow channels  40   a - 40   e  . . . by applying pressure and letting the preceding air escape through the polymer matrix. Filtered distilled water was similarly introduced in the upper (control) channel  38 . The flow channel  40  was then left at atmospheric pressure, while pressure was applied to the control channel  38 . For each value of the applied pressure, resistance was measured between the contacts  42  of each prong. The status of the respective valve  36  was also checked visually. Ionic redistribution in response to the applied DC field tends to increase the resistance of the channel  40  over time. While rapid measurements make this a small effect in the presented system, the polarity of applied voltage was reversed at every pressure setting to decrease the effect further. 
     As PDMS and glass were electrical insulators, it was a reasonable expectation that an uninterrupted channel  40  filled with a salty solution would drastically increase its electrical resistance if and only if it was pinched off by a closed valve  36 . Simple preliminary experiments confirmed that expectation. The observed effect establishes a 1-1 correspondence between channel resistance (low/high) and valve status (open/closed). The mechanical properties of the valve  36  establish another 1-1 correspondence, this time between the valve status (open/closed) and the applied pressure (insufficient/sufficient). Note that a single valve  36  does not directly report the value of the pressure, but reports if the applied pressure was below or above the valve&#39;s closing pressure. In essence, a single valve status produces a single inequality. Several such inequalities would narrow down the estimated pressure value better, especially if the respective bounds were judiciously selected. These bounds were the valves&#39; closing pressures. Closing pressure was tuned by varying the valve&#39;s dimensions. Then an array of valves  36  of different dimensions would provide the sought set of pressure inequalities. Larger valves  36  generally close at lower pressures. Hence, in principle, the applied pressure would be bound by the characteristic closing pressures of the largest open and the smallest closed valve  36 . The resulting interval estimate for the applied pressure would be as narrow as the interval between the bounds. This analysis suggested the basic scheme described above. 
     The scheme was implemented for applied pressures of 0.5 to 19 psi, in steps of 0.5 psi. The maximal value was set by the pressure at which all valves  36  were closed. Further increase in the pressure would not change the result, while pressures in excess of 20 psi significantly increase the risk of layer delamination. All flow-channel prongs had resistances between 26 and 64 MΩ when the valves  36  were open, while the resistance increased beyond the dynamic range of the multimeter (2 GΩ)) when and only when the respective valve  36  closed completely. 
     The graph of  FIG. 9   a  shows the characteristic closing pressure versus valve length, for each valve  36 .  FIG. 9   b  is a graph which shows the resistance pattern versus applied pressure. Since in certain cases multiple valves  36  closed at the same pressure, their resistance patterns practically overlapped. Consequently, multiple valves  36  in  FIG. 9   a  share one curve in  FIG. 9   b . The system can be used as a pressure gauge, wherein the measured resistance of each channel indicates the status of the corresponding valve  36  while the calibration ties that status to the applied pressure. For example, if all valves  36  up to and including the 65 μm valve  36  were in “high resistance” state, while all valves  36  above it were in “low resistance state”, then according to  FIG. 9   a , the applied pressure was between 10.5 and 11 psi. Alternatively,  FIG. 9   b  can be similarly used to arrive at the same conclusion. 
     It is clear that the accuracy of pressure measurement was dependent on the pressure spacing of data points in  FIG. 9   a , or of curves in  FIG. 9   b . The desired accuracy in each particular application would require different closing pressures and thus different dimensions.  FIGS. 7   a  and  7   b  show that high accuracy at high pressures cannot be achieved by varying only the valve length. However, if that restriction was relaxed, more values for the closing pressures become available and the pressure spacing can be shrunk accordingly, thereby improving accuracy.  FIG. 9   a  shows that valves  36  of lowest closing pressures generally break the rule that larger valves  36  close at lower pressures. Of course a simple initial calibration can allow the device to function correctly, but if a better programmability of properties was required, then fabrication parameters can be changed to shift the sensitive part of the  FIG. 9   a  curve to lower pressures. For example, decreasing valve membrane thickness would decrease the closing pressure for the same lateral dimensions. 
     Finally, a random fabrication artifact is believed to be responsible for the significant deviation of the 115 μm valve  36  from the general dependence in  FIG. 9   a . An individual glitch like that can be factored out trivially, as the pressure estimate was based on the results of the entire array. 
     Electro-Osmotic Peristaltic Micropump 
       FIG. 1   a  is a diagram showing microelectrodes  10  fabricated under a microfluidic channel  40 . If a DC voltage is applied to the first pair of electrodes  10   a  and  10   b , the available ions inside the water in the channel  40  redistribute themselves to produce a net charge profile as shown in the graph of  FIG. 1   b  which is simplistic linear approximation for ease of explanation. If the voltage is removed, the charges would redistribute themselves back to zero net charge everywhere. But, what if a DC voltage is applied to a second pair of electrodes  10   d  and  10   c , while the first pair  10   a  and  10   b  is still energized as illustrated in  FIG. 1   c , then the net charge distribution moves in the direction of the next pair as diagrammatically depicted in  FIG. 1   d.    
     Since both the positive and the negative peaks move in the same direction when the ions drag water molecules, it must be that there is a positive net flux of water in the same direction. Iterating this actuation down the channel  40  resembles a peristaltic wave, whence the pump is called a electro-osmotic peristaltic micropump  14 . 
     Clearly, there must be at least two pairs of electrodes  10  to break the symmetry and produce a preferred direction. In principle, a large number of stages allows multiple peristaltic waves to travel In the same direction simultaneously, thereby increasing the number of transported ions, and thus the amount of dragged water per unit time. However, a larger number of stages also means an overall bigger device, which could be disadvantageous, depending on the application. In general it is clear that the number of electrode pairs  10   a  and  10   b  and their spacing must be optimized for maximal throughput gained by minimal size of the device. 
     Once the ion packets reach the end of the device  14  as illustrated diagrammatically in  FIG. 1   e , the voltage is removed to restore the electrical configuration of device  14  to the initial stage shown in  FIG. 1   a . Then the driving sequence is reiterated. If each bit is given a value 1 for applied voltage and 0 for no applied voltage, then the described actuation sequence is {1000, 1100, 0100, 0110, 0010, 0011, 00001) for a four-stage pump  14 . 
     Other actuation sequences are also possible. For example, multiple peristaltic waves may be permissible, e.g,  FIG. 1   f . The peristaltic waves just have to be spaced enough to exclude mutual detrimental effects. For example, in  FIG. 1   f , the waves should not produce such problems. For example, the actuation loop for a six-stage device with a two-stage spacing between devices would be (100100, 110110, 010010, 011011, 001001, 001100). 
     Device  14  miniaturizes fluid propulsion and eliminates the need for outside pressure sources. Thus it would be an important step towards complete system miniaturization required, e.g. for handheld biomedical diagnostic devices. 
     Microsolenoids 
     The recent reduction to practice of microfluidic vias as disclosed by (PAU.59/CIT4467) U.S. patent application Ser. No. 11/502,135, filed on Aug. 19, 2006 entitled, “Integrated Microfluidic Vias, Overpasses, Underpasses, Septums, Microfuses, Nested Bioarrays And Methods For Fabricating The Same”, and incorporated herein by reference, and the concomitant easy access to truly three-dimensional multi-layer soft-lithography PDMS microfluidic devices opens new possibilities for architecture for device  14 . 
       FIG. 2   a  is a top plan layout view which shows one such structure, which can be stylized a two-string braid of microfluidic channels  40   a  and  40   b  defined in two levels of a microfluidic substrate and entwining with each other. In the  FIG. 1   a  the intertwining channels  40   a  and  40   b  are connected at their ends by a via  16 , thereby intertwining or jumping between an upper and lower level in a substrate. Channel segment  40   a  is define in an upper layer and then jumps by a via  16  to a lower level and then back up again at the next via  16  in an alternating fashion. The same topological approach can be realized in three-layer substrates, where the central channel  40   c  is in a middle layer as diagrammed in  FIGS. 2   b  and  2   c . There may be advantages to the embodiment of  FIGS. 2   b  and  2   c , e.g. tighter turns for a solenoid, at the expense of an extra layer of fabrication. 
     If one of the channels has metal electroplated into it, then a wire twisting around a microfluidic channel results. Such electroplating could be done by immersing the PDMS device  14  into a bath of suitable electrolyte, plugging an electrode  10  into one of the ports of the channel, and then applying a voltage between the bath and the port electrode  10 . The growth of electroplated material will follow the electric field lines and advance an edge from the starting electrode  10 . Thus a metal coating is formed in the corresponding channel  40 , thereby producing a self-assembled microwire. When current passes through such a wire, a magnetic field is established just like with a solenoid at the macroscale. 
     Electromagnetic Peristaltic Micropumps 
     This analogy gives rise to the name for the solenoid  14  of the embodiments of  FIGS. 2   a - 2   c  as a “microsolenoid”. The current that runs through the microsolenoid produces a magnetic field that attracts magnetic microbeads or nanoparticles inside the liquid within the entwined channel  40   c . The physics basis for this action is the magnetic force acting on a magnetic dipole in the presence of an outside magnetic field F=grad (m·B) where F is the force, m is the dipole moment, and B is the magnetic field (or flux density), Initially, no current is running through the solenoid  14 , there is no solenoid magnetic field, and the nanoparticle concentration is uniform along the channel  40   c  as diagrammed in the depiction  FIG. 3   a . When voltage is applied, electrical current runs along the “wire” of solenoid  14  comprised of the metallization formed in channels  40   a  and  40   b , and generates a magnetic field inside the solenoid cavity  22  in channel  40   c  in the proximity of a solenoid  14 . The nanoparticle dipoles tend to align itself with the external field. Then the scalar field of the dot product increases fastest towards the solenoid  14 , so the force is attractive. Once inside the solenoid cavity  22 , the scalar field is close to constant, so its gradient is minimal and thus the force decreases in magnitude. Thus the microsolenoids  20  can be utilized for an initial pull in their direction, which produces a compaction peak in the nanoparticle concentration in channel  40   c  as shown in  FIG. 3   b . Then another solenoid  14   b  downstream is activated while the upstream solenoid  14   a  has its voltage disconnected. The drop in the current will generate an EMF (electromotive force) in the upstream solenoid  14   a  while the increase in current in the downstream solenoid  14   b  will induce an additional EMF in the upstream solenoid  14   a , but none of these effects are important for nanoparticle behavior in channel  40   c . The collection of nanoparticles or molecules, collectively defined as the nanoparticle packet  18 , is now attracted to the downstream solenoid  14   b  and will stop moving only when it is inside the downstream solenoid  14   b  as shown in  FIG. 3   c . The propagation of this packet  18  will drag the liquid behind and thus produce pumping in the direction determined by the actuation sequence. 
     At least three solenoids  14   a ,  14   b ,  14   c  are necessary to produce a net flux in one direction, If only two are used, the packet  18  will oscillate between the two and thus produce an alternating pump, which would be useful for mixing or producing a nanopulsation, but not for overall net propulsion or movement of fluid in one direction. With three solenoid stages  14  however, the symmetry can be broken to allow net pumping in either direction, as determined by the actuation sequence depicted in  FIG. 3   d , much like peristalsis used by pneumatic pumping. 
     Distances must be optimized for best results. If the stages or solenoid turns  20  are too close to one another, the packet  18  propagates only a small distance with each solenoid  14  and thus the throughput per solenoid  14  could be low. In addition, solenoids  14  which are too close to each other require that fewer solenoids  14  to be energized at the same time to avoid backward forces on the downstream packets  18 . If the solenoids  14  are too far apart from another, then the attractive force to the next solenoid  14  would be quite weak and thus produce low acceleration, increasing the time between activation of successive solenoids  14 , thereby lowering the overall throughput. 
     Preliminary calculations show that a 150×100×10 μm packet  18  of 50% by volume of cobalt beads experience enough force from a single-turn 1 mA coil to generate effective static pressure of 0.5 psi and pressure differential of 2 Pa/μm. Also, since the magnetic force is maximal at distances equal to half the radius of the solenoid  14 , having more than 10 turns at channel dimensions of approximately 60 μm does not produce further gains due to diminishing returns, Still, a 10-turn solenoid is relatively compact, namely about 1 mm and produces enough pressure for transport. It should be noted that 5 psi static pressure difference produces typical flow speeds of 500 μm/sec in 100×10 μm channels  40  of 10 mm length. Such speeds are generated by pressure gradients of 3.3 Pa/μm, which is close to the expected pressure gradient generated by a single-turn coil. This is calculated to work a 1 mA currents, which generate dissipation rates of 0.1 Kelvin/sec for a single loop heating a 300×100×100 μm chunk of PDMS. If heating becomes a problem, larger channels can be integrated and filled with water to cool down the device as necessary. 
     Reversible Electromagnetic Microfilter and Microvalve 
     If one single stage  14  of such a pump as shown in any one of  FIGS. 3   a - 3   d  is utilized, it could serve as a reversible gate for the liquid in the channel  40 . Normally, nanoparticles would not interfere with the flow, especially if they are made small enough and coated with plastics to make then neutral-buoyant in water or the fluid. However, if the solenoid  14  is activated, then the local concentration of particles would peak and thus temporally produce a sieve through which the water must pass. So long as the magnetic force on the nanoparticle is stronger than the drag force from the water or fluid, the “sieve” or “plug” would remain in place. The calculations above show that this is feasible. Thus, filtering would be produced for low nanoparticle concentrations, while a real valve  36 , albeit possibly a leaky one, would be produced for high concentrations. Both devices would be reversible, since switching off the electrical current would let the “sieve” or “plug” dissipate and thus normal flow would proceed as before. 
     In this scenario, the liquid must be propelled by an agency external to these two devices. Such might be simple static pressure or perhaps an electromagnetic micropump upstream or downstream from the filter/valve device. 
     Micromagnetometer 
     Finally, microsolenoids  14  as shown in any one of  FIGS. 3   a - 3   d  can be used as magnetometers. e.g. for single-cell MRI (magnetic resonance imaging), for sensing magnetotactic bacteria, and for cell-sorting based on magnetic nanoparticle tags. In these cases, the microsolenoid  14  is connected to a sensitive ammeter to measure the current resulting from EMF induced by the change of magnetic field as magnetic material approaches and passes through the solenoid  14 . 
     Electrolysis Microvalves 
     An often unwanted side effect in micro-electromechanical systems (MEMS) is electrolysis of water and bubble formation at high-electric-field locations in the device. This effect can be utilized to actuate PDMS microfluidic valves  36 . If two electrodes  10  are fabricated to coincide with a dead-end channel  40 , then applying enough voltage across the electrodes  10  produces electrolysis of water into an expanding bubble of oxygen and hydrogen gas  12  as shown in  FIG. 10 . The small dimensions ensure that even a modest voltage produces high electric fields, since V=E*d. The gas  12  of electrolysis expands and provide the pressure to close a valve  36  pneumatically as before. Significantly, the pressure does not need to be generated at the valve  36  itself, which simplifies the device architecture and makes it compatible with current designs. For example, as single pair of electrodes  10  can actuate an array of valves  36  by use of the conventional connectivity of control channels  38  and channel crossovers. 
     The electrodes  10  typically can be fabricated in the chip substrate, which makes connections to pushup valves  36  straight forward. The use of vias  16  can do the same for pushdown devices. Since PDMS is permeable to gases, the generated oxygen and hydrogen escapes through the polymer matrix over time. This means the pressure drops and the valves  36  eventually open. If such opening is desirable, no further action is required. If not, voltage can be reapplied to the electrodes  10  periodically to generate more gas. 
     The ignition frequency can be used to tune the magnitude of the resulting pressure as may be desired. Dimensions would have to be optimized to allow rapid evacuation of the generated gas (e.g. by high surface-to-volume ratio) if fast response is required, e.g. for pumping. Alternatively, where speed is not a priority, a low surface-to-volume ratio allows maintenance of the generated pressure by less frequent ignitions. Oxygen produces charring of the PDMS, so liquids other than water can be selected instead. However, water is the simple obvious inexpensive robust solution. Each ignition requires only a small amount of gas generated to actuate the valves  36  since air is about 1,000 times less dense than water at atmospheric pressure. Thus, the losses of water due to the valve actuation are not significant next to the available volume in the channel. For applications requiring high frequency of actuation over a long time, the control channels  38  may be made bigger to serve as a water reservoir, or the macroworld interface port, which is used to insert the water in the first place, could be used as such a reservoir. To make certain that bubbles  12  do just push water out of the port, the port can be sealed off with a plug during the chip&#39;s initial setup. Electrolysis microvalves  36  could solve the problem of pressure control miniaturization, thereby enabling full system miniaturization and truly portable or handheld devices. 
     Electrolysis Micropumps 
     Just as pneumatic valves can be organized to produce pneumatic pumps as has been done in the prior art, electrolysis microvalves  36  could be organized to produce electrolysis micropumps  14  in a manner similar to that described above. The same ideas can then be applied for pumping in one direction, to-and-fro, or in a circle. Thus such micropumps  14  enable full system miniaturization for handheld devices. 
     The presented new electrical microdevices enhance and expand the capabilities of PDMS microfluidic technology and its scope of applications, by replacing external macroworld pneumatic control with internal microworld electric control. The latter allows whole system miniaturization and thus the advent of truly portable and handheld devices, e.g. for decentralized biomedical diagnostics. 
     Many alterations and modifications may be made by those having ordinary skill in the art without departing from the spirit and scope of the invention. Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following invention and its various embodiments. 
     Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following claims. For example, notwithstanding the fact that the elements of a claim were set forth below in a certain combination, it must be expressly understood that the invention includes other combinations of fewer, more or different elements, which were disclosed in above even when not initially claimed in such combinations. A teaching that two elements were combined in a claimed combination was further to be understood as also allowing for a claimed combination in which the two elements were not combined with each other, but may be used alone or combined in other combinations. The excision of any disclosed element of the invention was explicitly contemplated as within the scope of the invention. 
     The words used in this specification to describe the invention and its various embodiments were to be understood not only in the sense of their commonly defined meanings, but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus if an element can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself. 
     The definitions of the words or elements of the following claims were, therefore, defined in this specification to include not only the combination of elements which were literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense it was therefore contemplated that an equivalent substitution of two or more elements may be made for any one of the elements in the claims below or that a single element may be substituted for two or more elements in a claim. Although elements may be described above as acting in certain combinations and even initially claimed as such, it was to be expressly understood that one or more elements from a claimed combination can in some cases be excised from the combination and that the claimed combination may be directed to a subcombination or variation of a subcombination. 
     Insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, were expressly contemplated as being equivalently within the scope of the claims. Therefore, obvious substitutions now or later known to one with ordinary skill in the art were defined to be within the scope of the defined elements. 
     The claims were thus to be understood to include what was specifically illustrated and described above, what was conceptionally equivalent, what can be obviously substituted and also what essentially incorporates the essential idea of the invention.