Abstract:
A low voltage control circuit is provided for individually controlling high voltage power provided over bus lines to a multitude of interconnected loads. An example of a load is a drive for capillary channels in a microfluidic system. Control is distributed from a central high voltage circuit, rather than using a number of large expensive central high voltage circuits to enable reducing circuit size and cost. Voltage is distributed to each individual load and controlled using a number of high voltage controller channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator switching controlled from the central high voltage circuit to provide a desired bus line voltage. Switching of the photo isolator relays is further controlled in each channel switch using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. Current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit.

Description:
BACKGROUND 
     1. Technical Field 
     The present invention relates to a voltage controller system for providing stable high voltage bus line voltages using low voltage control signals while minimizing circuit cost and size. More particularly, the present invention relates to a voltage control system for providing a number of high voltages over bus lines to drive capillary channels in a microfluidic system. 
     2. Related Art 
     Microfluidic systems are used for the acquisition of chemical and biochemical information. A microfluidic system refers to a device having channels that are generally fabricated at the micron or submicron scale with channel dimensions on the order of 5–100 micrometers. Fabrication of such fluidic microcapillary devices is provided using photolithography and chemical etching processes applied to silicon or glass substrates, techniques typically used in the semiconductor electronics industry. Applications of microfluidic systems include capillary electrophoresis, liquid chromatography, flow injection analysis, and chemical reaction and synthesis. 
     One method to transport fluids in capillaries of a microfluidic system uses voltages applied across channels in the system to create electric fields, with electrokinetic forces serving to move fluid materials through the channels. Electrokinetic forces have the advantages of direct control, fast response and simplicity. 
     To control fluid flow in capillaries of a microfluidic system requires a precise voltage to be applied across a number of channels. Microfluidic systems typically use a network of channels in a substrate. The channels connect a number of fluid reservoirs in contact with high voltage electrodes. To move fluid materials through the network of channels, specific voltages are applied to the various electrodes provided in reservoirs at the end of channels. 
     Voltages applied to the electrodes in the device can be high, for example up to thousands of volts per centimeter. High voltage supplies typically required for each electrode are expensive and bulky. Thus the cost of a complex microfluidic system using electrokinetic forces for fluid movement may be prohibitive. 
     SUMMARY 
     In accordance with the present invention, a power distribution system is provided which may be used to provide voltages to loads, such as electrodes in a microfluidic system. In the system individually controlled channel switching circuits are provided to distribute power from a central high voltage supply circuit. The individual channel switching circuits, less complex than the central supply, distribute power to enable a reduction in cost and size from the use of multiple central high voltage supplies, typically making up a power distribution system. 
     In the system according to the present invention, voltage is distributed to each individual load (or electrode) and controlled using the channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator relay switching controlled from the central high voltage supply to provide a desired bus line voltage. The ability of the photo isolator relays to switch current of varying amounts enables precise control of voltage on each bus line. 
     In addition to control from the central power supply, switching of the photo isolators is further controlled in each channel switch circuit using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. The divider circuit lowers the read-out voltage of the channel node so that special high-voltage voltmeters are not required. The divider circuits are also designed to draw negligible currents from the channels thereby minimizing unwanted electrochemical effects, such as gas generation if the system is used to control a microfluidics system. 
     Further in accordance with the present invention, current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit. Such measurement of electrical current in each channel can be used to provide a direct measure of fluid flow through the channels of a microfluidic system. 
     Thus, in one embodiment the system of the present invention is used to provide voltages to control a plurality of interconnected capillary channels of a microfluidic system. The voltages are applied to a plurality of electrodes at different nodes of the capillary channels to create electric fields in the capillary channels to electrokinetically move fluids. The voltages applied are set by the central high voltage control circuit and applied through signals to the individual channel switch circuits. Programmable control using the central high voltage control circuit with current measurement feedback enables precise control of fluid movement through a plurality of interconnected capillary channels. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further details of the present invention are explained with the help of the attached drawings in which: 
         FIG. 1  shows a diagram of a portion of a microfluidic system with a power distribution system according to the present invention; 
         FIG. 2  shows details of the channel switching circuit of  FIG. 1 ; 
         FIG. 3  shows additional channel switching circuits configured to provide negative bus line output voltages; 
         FIG. 4  shows components, which can be added to the channel switching circuits of  FIG. 1  to measure current flow from their respective bus lines; 
         FIG. 5  shows a configuration of circuitry for measuring current flow when a higher output voltage is provided; and 
         FIG. 6  shows details of the power supply &amp; control circuit of  FIG. 1 . 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  shows a diagram of a portion of a microfluidic system with a power distribution system according to the present invention. The power distribution system includes a power supply &amp; control unit  2  that supplies both power and control signals to a plurality of channel switching circuits  4 . The channel switch circuits  4  distribute voltage signals over power supply bus lines  6  to individual electrodes  11 – 15  provided in reservoirs  21 – 25  of a microfluidics system. 
     The reservoirs  21 – 25  are fluidly connected at the ends of channels  31 – 33  to form the microfluidics system. The microfluidics reservoirs and channels are formed in a planar substrate  27 . The microfluidic system transports fluids from reservoirs  21 – 25  through the various channels  21 – 23  of substrate  27 . To move materials through the channels  21 – 23 , the channel switching circuits  4  apply selectable voltage levels, including ground, to each of the reservoirs  21 – 25 . Power is supplied to the channel switching circuits  4  along with control signals to set the bus line voltages from the power supply &amp; control unit  2 . 
     The channel switch circuits  4  include relays to apply high voltage signals over bus lines  6  to the electrodes  11 – 15 , and voltage dividers for feedback control to maintain the voltages to a desired value. The channel switch circuits  4  further include current flow sensors connected to each electrode  11 – 15  to enable monitoring of fluid flow. Components of the channel switch circuits  4  are described in more detail with respect to  FIGS. 2 and 3 . 
     The power supply &amp; control unit  2  provides the high voltages to the relays of the channel switching circuits  4 , along with control signals to enable the voltage on each bus line to be precisely set. More details of the power supply and control unit  2  are described subsequently with respect to  FIG. 6 . 
       FIG. 2  shows details of the channel switch circuits  4  of  FIG. 1 , as connected to the power supply and control unit  2 . The channel switch circuits  4  shown include circuits  4   1 – 4   4 . Each of the channel switch circuits  4   1 – 4   3  has similar components, so details are described with respect to the channel switch circuit  4   1 . The channel switch circuit  4   1  includes a complementary switch  50  with a pair of photo optical isolator relays  51  and  52 . Bach photo isolator has an isolated input operating at a low voltage in the range of 1–5V, and a relay output operating in the range of +1 KV. The photo isolator relays  51  and  52  are controlled by a signal from feedback amplifier  54 . An example of the photo isolator relay is the AROMAT photoMOS solid-state relay AQV-258. 
     The photo isolators  51  and  52  operate as a complementary pair. In photo isolator  51 , the relay output has a first terminal connected to a bus line BS 1  supplying a channel, and a second terminal connected to a high voltage power supply connection Vsup 1 , providing on the order of 1000 volts to drive the bus line BS 1  to a variable potential up to 1000 volts when sourcing current. Vsup 1  is provided from the power supply &amp; control unit  2 . The relay output of photo isolator  52  has a first terminal connected to the bus line BS 1  and a second terminal connected to ground to drive bus line BS 1  to a variable potential down to ground when sinking current. A common input signal from the feedback amplifier  54  drives the photo isolators  51  and  52  to turn on and off to set the voltage on line BS 1  to a desired level. One aspect of the present invention takes advantage of the fact that the photo isolators  51  and  52  turn on in varying degrees depending on the input signal, similar to a pair of complementary MOS transistors typically used to form a CMOS op-amp. 
     The photo isolator relays  51  and  52  provide a relay output switching power to a supply capacitor  77 . The supply capacitor is sized to support a desired load level. Diodes  57  and  58  are connected to the inputs of the photo isolators  51  and  52  to turn on the photo isolators  51  and  52  in a complementary fashion as controlled by a single input signal from the feedback amplifier  54 . A voltage Vset connected to a second input terminal of each of the photo isolators  51  and  52  is set to a desired threshold switching voltage. In one embodiment Vset is provided at 2.5V with 0–5V drive voltages provided to diodes  57  and  58 . The voltage Vset can be supplied from the power supply &amp; control unit  2 . 
     With the voltage on the bus lines being very high (on the order of 1 KV) while control voltages are much lower (on the order of 5V), a voltmeter directly measuring the voltage on a bus line, such as BS 1 , must have a very high input impedance. Such voltmeters are expensive. To avoid costs of voltmeters, the bus line BS 1  is connected to a voltage divider circuit formed by series resistors  61  and  62 . The central terminal of the series resistors  61  and  62  provides a significant voltage reduction from the voltage on line BS 1 , and is carried as a feedback input to feedback amplifier  54 . As shown for explanatory purposes, the voltage on BS 1  is divided on the order of a 200-to-1 ratio to provide the feedback signal for amplifier  54 . The feedback signal provides a control voltage to maintain the voltage BS 1  at a desired level. 
     A second input of the feedback amplifier  54  is connected to a voltage reference S 1  provided from the power supply and control unit. The signal S 1  is an analog signal varying from 0–5V and is controlled to set the voltage on BS 1  to a desired value. Separate control voltages S 2 –S 4  are provided to individually control the bus lines BS 2 –BS 4  for channel switch circuits  4   2 – 4   4 . 
     The arrangement of the photo isolator relays  51  and  52  in the channel switch circuits  4   1 – 4   3  allows current sourcing or sinking at a constant voltage. Current sourcing or sinking while providing a constant voltage is essential for any power supply used for microfluidic systems. 
     The channel switch circuits  4   1 – 4   3  provide one embodiment of a channel switch circuit that can supply voltages on the order of 1 KV. The channel switch circuit  44  provides a second embodiment for controlling a slightly higher output (shown here as 5 KV). The circuit  44  includes a conventional DC-DC converter circuit  70  for converting a low voltage input, such as 0.7–5.0V, to a high voltage output, shown as 5 KV. An example of such a DC-HVDC converter is the Q50-5 manufactured by EMCO Corporation of Sutter Creek, Calif. As with the circuits  4   1 – 4   3 , the circuit  4   4  includes a voltage divider made up of a series pair of resistors  71  and  72  has a common terminal connected to provide a low voltage feedback signal to a feedback amplifier  75 . A second terminal of resistor  72  is connected to an output return (OUT RTN ) of the DC-DC converter  70 , as well as to a virtual ground. A virtual ground can be provided at the input of a differential amplifier, such as the amplifier  120  of  FIG. 5  discussed subsequently. A second terminal of resistor  71  connects to the bus line output BS 4 , and is connected to the positive output (OUT+) of the DC-DC converter  70 . A load capacitor  76  connects the bus line BS 4  to ground. 
     The output terminals OUT+ and OUT RTN  are connected by a capacitor  78 . The capacitor  78  serves to reduce the high frequency noise radiated by the DC-DC converter  70 . To reduce noise, it is further preferable to wrap or encase the DC-DC converter circuitry  70  in electrically ground material, for example copper tape. Without such steps to reduce noise, circuitry included nearby, such as the current sensing circuitry discussed subsequently in  FIG. 4  will experience significant interference. 
     The feedback signal for the common terminal of resistors  71  and  72  is connected to the negative input of a feedback amplifier  75 . A positive input of the amplifier is controlled by a signal S 4  from the power supply &amp; control unit  2 . The output of the feedback amplifier  75  drives the base of transistor  79 . Transistor  79  connects the supply voltage Vcc (approximately 5V for the DC-DC converter  70  shown) to the positive input IN+ of the DC-DC converter  70 . The negative input IN− is connected to ground. The signal S 4  is an analog signal with transitions controlled to set the output on bus line BS 4  up to +5 KV, as shown. Feedback assures that the output BS 4  remains at the desired 5 KV level. 
       FIG. 3  shows additional channel switching circuits  4   5 – 4   8  which provide negative bus line outputs BS 5 –BS 8 . As with the channel switching circuits  4   1 – 4   3 , the channel switching circuits  4   5 – 4   7  include similar components, so components for circuits  4   5 – 4   7  will be described with respect to circuit  4   5 . The channel switching circuit  4   5  includes a complementary switching circuit  80  and feedback amplifier  94 . The complementary switching circuit  80  includes complementary photo isolator relays  81  and  82  similar to relays  51  and  52  of  FIG. 2 . The photo isolator relays are driven by diodes  87  and  88  using a single output from the feedback amplifier  94 , similar to diodes  57  and  58  and their connection to feedback amplifier  54  in  FIG. 2 . Second input terminals of photo isolator relays  81  and  82  are connected to a threshold voltage Vset. Unlike the complementary switch  50 , the pull up photo isolator relay  81  connects the bus line BS 5  to ground, while the pull down isolator relay  82  connects the bus line BS 5  to a negative voltage Vsup 2 , shown as −1 KV. The high negative voltage Vsup 2  is provided from the power supply and control unit  2 . 
     Series resistors  91  and  92  provide feedback to the amplifier  94 , similar to resistors  61  and  62  and their connection to feedback amplifier  54  of  FIG. 2 . However, unlike the series resistors  61  and  62  that connect bus line BS 1  to ground, series resistors  91  and  92  connect the bus line BS 5  to a voltage Vcc. In one embodiment, Vcc is set to approximately 5.0 volts. The common terminal of resistors  91  and  92  provides an inverting input to feedback amplifier  94 , while the non-inverting input is an analog switching signal S 5  provided by the power supply &amp; control unit  2  to set the voltage on line BS 5  to a desired level. Analog switching signals S 5 –S 7  are likewise provided to circuits  4   5 – 4   7  to set their outputs BS 5 –BS 7  to desired levels. A capacitor  95  connected to the bus line is sized to drive the output. 
     The channel switching circuit  4   8  is configured to drive a greater negative voltage, shown as −5 KV, than the circuits  4   5 – 4   7 , shown to drive −1 KV, and has components similar to the circuit  4   4  of  FIG. 2 , shown driving +5 KV. The circuit includes a DC-DC converter  100  with series resistors  101  and  102  connecting its output terminals, similar to the DC-DC converter  70  and resistors  71 – 72  of  FIG. 2 . As with DC-DC converter  70 , the output OUT RTN  of the DC-DC converter  100  is connected to a virtual ground, which may be provided by an amplifier, as discussed subsequently with respect to  FIG. 5 . One of example of a circuit which may be used for the DC-DC converter  100  is the Q50N-5 manufactured by EMCO Corporation. A load capacitor  106  connects the negative output OUT− at bus line BS 8  to ground. Unlike the DC-DC converter  70  of  FIG. 2 , the DC-DC converter  100  has a positive input connected to Vcc, and a negative input connected through an emitter to collector path of transistor  109  to ground. The base of transistor  109  is driven by the feedback amplifier  105 . Like the capacitor  78  connecting the output terminals of DC-DC converter  70  in  FIG. 2 , a capacitor  108  connects the outputs of DC-DC converter  100  to reduce noise. Further, to reduce noise, the DC-DC converter  70  is wrapped in copper tape, or otherwise grounded. 
     The outputs BS 1 –BS 8  are connected in one embodiment to electrodes in a microfluidics system to control movement of fluids. Signals S 1 –S 8  are then set using a processor to control voltages on bus lines BS 1 –BS 7  to control fluid movement in the microfluidics system. Although described with use in a microfluidics system, it is understood that the power supply system described with respect to  FIGS. 2 and 3  can be used to supply high voltages to other systems. 
     In addition to providing controlled high voltage outputs on bus lines, in one embodiment measurement is provided of current drawn from the nodes BS 1 –BS 7 . For a microfluidics system, current flow at a given electrode is directly related to the rate of fluid flow along the channel(s) connecting the reservoir in which the electrode is placed. Voltages on the electrodes of the microfluidic system can be set in response to the electric currents flowing through the various electrodes to control fluid movement. 
       FIG. 4  shows components that can be added to the channel switch circuits,  4   1 – 4   3  of  FIG. 2  or  4   5 – 4   7  of  FIG. 3 , labeled as  4   N  in  FIG. 4 , to measure current flow from their respective bus lines BS 1 –BS 3 , or BS 5 –BS 7 , labeled as BS N  in  FIG. 4 . For reference, a portion of the circuit components used in the channel switching circuits are carried over from circuits  4   1 – 4   3  and  4   5 – 4   7  to form channel switch circuit  4   N  in  FIG. 4 . The current measurement circuit of  FIG. 4  adds a resistor  110  in the path between the bus line output, labeled BS N , and a load capacitor  113 . A field effect transistor (FET)  112  then is placed with its source to drain path in parallel with the resistor  110 . The source and gate of transistor  112  are connected by a large resistor  114  to reduce the effect of parasitic capacitance when a gate clock signal is applied. An isolating capacitor  115  is placed between the gate of transistor  112  and a clock input. The capacitor  115  AC couples a square wave clock signal to the transistor  112 , while capacitor  118  AC couples out a resulting harmonic square wave created having an amplitude proportional to the measured current. 
     In operation, a clock signal is applied from the power supply and control unit  2  to turn transistor  112  on and off to provide either a direct (short circuit) path between the channel switch circuit  4   N  and the output BS N , or a path through resistor  110 . The measured voltage difference between when the transistor  112  is on and off can then be used to determine current flow. Voltage is measured using a voltage follower amplifier  116  having its inverting input and output connected together, and its non-inverting input connected through an isolation capacitor  118  to the drain of transistor  112  at the output BS N . The system voltage Vcc/2 is applied through a resistor  120  to bias the non-inverting input of amplifier  116 . 
       FIG. 5  shows current sensing circuitry to be added to the higher voltage channel switching circuits  4   4  and  4   8 , shown in  FIG. 5  as  4   M . A portion of the channel switching circuitry components are carried over from circuits  4   4  and  4   8  in channel switching circuit  4   M  of  FIG. 5  for reference. The current measurement circuitry is provided from the output of a transimpedance amplifier  120  having an inverting (−) input connected to the return output OUT RTN  of the DC-DC converter of circuit  4   M , and a (+) non-inverting input connected to a voltage reference. The voltage reference is provided from the common terminal of series resistors  122  and  124 , with a second terminal of resistor  122  connected to Vcc and a second terminal of resistor  124  connected to ground. A parallel resistor  126  and capacitor  128  are connected from the output of amplifier  120  to its inverting input, while a capacitor  129  connects the noninverting input of amplifier  120  to ground to provide an appropriate bias and feedback. 
     As part of the current monitoring circuit of  FIG. 5  for the ±5 KV supplies, the bottom of the voltage divider circuit (formed by series resistors  71 , 72  or  101 , 102 ) connects to the inverting (−) input of a transimpedance amplifier  120  to form a virtual ground. To assure proper amplifier biasing while providing a virtual ground, the voltage Vcc applied to resistor  122  can be raised slightly above the system voltage with the raised system voltage applied as Vcc to the DC-DC converters. For example with the system voltage Vcc being 5.0 volts, 5.12 volts could be used as the raised system voltage. As such, the virtual ground of transimpedance amplifier  120  will be 0.12 V (for the +5 KV) version or 5.00 V (for the −5 KV version) exactly 0.12 V away from the 5.12 volt supply or ground. 
     In one embodiment of the present invention, to provide precise feedback control if tight tolerances are required for the outputs BS N , one of the series feedback resistors is made a variable resistor. Such a variable resistor is illustrated as component  111  in  FIG. 4 , and component  121  of  FIG. 5 . The variable resistor can be a potentiometer, allowing interactive control by a user, or it can be set during manufacture by physically trimming the resistors. 
       FIG. 6  shows a portion of the components of the power supply &amp; control unit  2  of  FIG. 1  used to generate the reference voltages Vsup 1 , Vsup 2  and Vcc. The power supply &amp; control unit  2  includes the control unit  150  which generates control signals, such as S 1 –S 4  of  FIG. 1 . The control unit  150  shown further provides internal control signals AS 1  and AS 2  used to set the voltage references Vsup 1  and Vsup 2  to desired values. The power supply portion of the power supply and control unit  2  includes a first power supply circuit  51  for generating the signal Vsup 1 , a second power supply circuit  52  for generating the signal Vsup 2  and a third power supply circuit for generating Vcc. 
     The first power supply unit  51  includes a DC-DC converter  152  for converting a 0.7–5.0V input to a +1 KV output. A first output terminal OUT+ of the DC-DC converter  152  provides the +1 KV reference voltage Vsup 1 . A capacitor  154  supporting the intended load for Vsup 1  is connected from the output OUT+ to ground, while series resistors  156  and  158  connect the output OUT+ to ground, and have a central terminal providing a feedback control signal. The feedback signal is provided to an inverting input of an amplifier  160 . A non-inverting input of amplifier  160  receives the analog input control signal AS 1 . The output of feedback amplifier  160  is connected to a first input IN+ of the DC-DC converter  152 . A second input IN− and return output OUT RTN  of the DC-DC converter  152  are both connected to ground. 
     The second power supply unit  52  includes a DC-DC converter  172  for converting a 0.7–5.0V input to a −1 KV output. A first output terminal OUT− of the DC-DC converter  172  provides the −1 KV voltage reference Vsup 2 . A capacitor  174  supporting the intended load for Vsup 1  is connected from the output OUT− to ground, while series resistors  176  and  178  connect the output OUT− to Vcc, and have a central terminal providing a feedback control signal. The feedback signal is provided to an inverting input of an amplifier  180 . A non-inverting input of amplifier  180  receives the analog input control signal AS 1 . The output of feedback amplifier  180  is connected to a first input IN− of the DC-DC converter  172 . A second input IN+ is connected to Vcc, while the return output OUT RTN  of the DC-DC converter  152  is connected to ground. 
     The third power supply unit  53  provides a stable system voltage Vcc from a battery voltage V BAT . The current at the output supplying Vcc is controlled using a current mode switching regulator  200 . An example of the current mode switching regulator is the LTC1147-5 manufactured by Linear Technologies Corporation. The regulator  200  basically is a pulse width modulation (PWM) voltage regulator, mainly employing MOSFET  210 , inductor  206 , and free-wheeling diode  218  to chop and filter the input voltage to a lower regulated output voltage at high efficiency (&gt;90%). A battery input voltage V BAT  provides the control input V IN  of the switching regulator  200  and the source voltage of FET  210 . The drain voltage of FET  210  is then connected through an inductor  211  and resistor  212  to provide the circuit output Vcc. Sensing of current is provided by the current mode switching regulator  200  using SENSE+ and SENSE− connections across resistor  212 . Current control is then provided from the DRIVE output of switching regulator  200  to the gate of transistor  210 . Feedback for the current controller is provided using series resistors  214  and  216  connected from the output providing Vcc to ground, with the common terminal of resistors  214  and  216  connected to the feedback input V FB  of the current mode switching regulator  200 . A load capacitor  220  is connected across the sense inputs SENSE+ and SENSE− of the current controller  220 . 
     Although the present invention has been described above with particularity, this was merely to teach one of ordinary skill in the art how to make and use the invention. Many additional modifications will fall within the scope of the invention, as that scope is defined by the claims that follow.