CN102175844A - Multifunctional microfluid control device for operating biochemical fluids in microfluid control chip automatically - Google Patents
Multifunctional microfluid control device for operating biochemical fluids in microfluid control chip automatically Download PDFInfo
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- CN102175844A CN102175844A CN2011100261633A CN201110026163A CN102175844A CN 102175844 A CN102175844 A CN 102175844A CN 2011100261633 A CN2011100261633 A CN 2011100261633A CN 201110026163 A CN201110026163 A CN 201110026163A CN 102175844 A CN102175844 A CN 102175844A
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Abstract
The invention provides a multifunctional microfluid control device for operating biochemical fluids in a microfluid control chip automatically. The device consists of a system control module, electric drivers of six paths of direct-current high voltages, hydraulic drivers of two paths of micro-injection pumps, dielectrophoretic devices of two paths of sine waves and program software. The multifunctional microfluid control device has the characteristics that: through arbitrary combination of six paths of the direct-current high voltages (disconnection, voltage/connection and grounding), two paths of the micro-injection pumps (front waiting, propelling/injection, back waiting and withdrawal) and two paths of the sine waves (front waiting, sine wave and back waiting), independent or/and synchronous programmable control, rapid switching and stable output, the automatic operation on different biochemical fluids in the microfluid control chips with different structures is facilitated; and biochemical analysis on the microfluid control chip with strong establishing adaptability and small error range is more flexible and more simple and convenient.
Description
Technical field:
The invention belongs to micro-fluidic instrument platform technology, particularly a kind of current collection driving, hydraulic-driven, dielectrophoresis and full automation are controlled in the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip of one.
Background technology:
Micro-fluidic chip (microfluidic chip) because of its have low consumption, quick, multiple analytic function can be integrated etc. advantage become the important platform of field microanalysiss researchs such as biology, chemistry in recent years.Because the micro-fluidic chip analysis is on several square centimeters of chips, in the micron order compartment analysis passage of network characterization, by rising even the quick manipulation of skin upgrading sample scale, and realize a kind of novel analytical technology of operations such as the related specimen preparation of biochemical test, sample introduction, mixing, reaction, separation, detection to receiving.Therefore, for the micro-fluidic chip analytic system, want and the logotype well of above-mentioned advantage, the automatic manipulation problem that effectively solves biochemical fluid is extremely urgent.
In recent years, the method that is used for micro-fluidic chip fluid drives and control in the world mainly relies on two class manipulation technologies: have little valve on the chip or/and the valve controlled pump technology of Micropump device and dynamic flow technology continuously.The flow direction of valve controlled pump Technology Need (machinery) Micropump drive fluid, valve control fluid.Its advantage is to be convenient to microminiaturization.Its shortcoming is: because comprise miniature movable member, the chip manufacture difficulty is big, cost is expensive, the performance of little valve is relatively poor relatively, has that back pressure is low, problems such as leakage and dead volume, effect is difficult to satisfactory.The dynamic flow technology comprises two kinds of mechanical type (Micropump) and on-mechanicals continuously.The machinery Micropump is such as syringe pump, air driven pump, piezoelectric pump etc., generally by moving liquid-solid and liquid-liquid interface liquid mobile applied vibrations or revolving force comes drive fluid.Its advantage be simple to operate, convection cell character does not require, can provide with the low discharge of chip microchannel coupling and carry.Its shortcoming is the flow direction that is difficult to control fluid, it is integrated to be not easy with chip.The continuous dynamic flow technology of on-mechanical, such as: electric driving, dielectrophoresis, optical drive and magnetic driving etc., then rely on to be applied to the driving operation that the electricity, light, the magnetic homenergic that are driven on the fluid provide fluid, direction of flow then is to control by the direction of external energy field.Or/and the electricity of principle of electrophoresis drives, is topmost microfluidic manipulations means during present micro-fluidic chip is analyzed based on electric osmose.Electricity drives with the drive controlling source of impressed voltage (electric field) as fluid, be applied to voltage on the chip pond at night by synchronization modulation, the voltage of chip crossing (economize on electricity) can be regulated artificially, thereby the size and Orientation of chip crossing can be regulated and control to electric field intensity between each liquid pool; When different microchannels produce different in flow rate, the direction that control crossing fluid flows, the function of realization valve; And then finish operations such as the sample introduction of micro-fluidic chip in analyzing, separation.Electrically driven (operated) advantage is: no movable member, liquid flow pulse free, flow are moderate, easy and simple to handle, flexible, easily and chip integrated.Its shortcoming is to the tube channel wall material and is driven the physicochemical properties of fluid sensitivity.Based on the dielectrophoresis of polarizable particle in the fluid, be to utilize to exchange to induce the interaction that produces free charge to drive and control fluid in low-voltage (sine wave) and the fluid interface.Its advantage is: no movable member, little, easy and simple to handle, flexible to biofluid damage, easily and chip integrated.Its shortcoming is: chip structure complexity, little, the suitable low conductivity (10 of driving force
-12-10
-6S/m) fluid.Optical drive and magnetic drive, and generally are to add " light-thermo-responsive nano particle " or new materials such as " close magnetic nano-particle media " in institute's conveyance fluid, excite by optical excitation or magnetic and realize fluid-operated a kind of novelty trial.Advantage is to be particularly suitable for driving the nanochannel inner fluid.Shortcoming is: owing to optical focus difficult relatively and magnetic field " dispersiveness ", the device preparation is complicated, and driving mechanism waits further research.
Current, in order on micro-fluidic chip, to realize the biochemical analysis of cell, molecular level, require the flow of fluid between chip channel, moving phase to form and flow to controlledly, and do not disturb the biological primary characteristic and the stability of analytic system work.In addition, also require the microfluidic manipulations technology constantly to develop to multifunctional integrated and full automatic direction.Present problem is, because the flow characteristics between all kinds of biofluids (as the cell fluid), chemical fluid and biofluid and the chemical fluid exists than big-difference, existing microfluidic manipulations technology is applied to the micro-fluidic chip biochemical analysis and also has following deficiency: 1) drive pattern is single, some of them (driving as optical drive, magnetic) are just emphasized the special applications that drives, and versatility is not strong; 2) a spot of combination drives and also has only two kinds of drive patterns, for example: (gravity) hydraulic-driven-electricity drives, and constitute the simple combination mostly equipment that combination drives is each independent instrument, exist control the response time inconsistent, influence deficiency such as chip analysis reappearance.
For satisfying the needs of micro-fluidic chip biochemical analysis, the present invention integrates the electricity driving of microchip analytical approach, six tunnel high direct voltages, the hydraulic-driven of two tunnel micro syringe pump, the dielectrophoresis and the full automatic microelectronics control technology of two road sine waves, and a kind of multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip is provided.Characteristics of the present invention are: output is controlled, is switched and stablize fast in the combination in any of six tunnel high direct voltages, two tunnel micro syringe pump and two road sine waves, sequencing, be convenient in the different structure micro-fluidic chip, finish the unmanned operation of different biochemical fluids, make that the establishment micro-fluidic chip biochemical analysis that adaptability is strong, error range is little is more flexible and easy.
Summary of the invention:
Purpose of the present invention is intended to overcome the deficiencies in the prior art part, a kind of multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip is provided, promptly can realize the integrated of " the electricity driving of six tunnel high direct voltages, the hydraulic-driven of two tunnel micro syringe pump, the dielectrophoresis of two road sine waves " three kinds of drive patterns and full automation control by the present invention, be convenient in the different structure microchip, finish the automatic manipulation of different biochemical fluids, satisfy the needs of micro-fluidic chip biochemical analysis.
Purpose of the present invention can realize by following technical measures:
It is made up of system control module, electric driver module, hydraulic-driven module, dielectrophoresis module and program software, wherein:
Described system control module is the control core with the chip microprocessor, described electric driver module is six tunnel high direct voltages, described hydraulic-driven module is two tunnel micro syringe pump, and it is two road sine waves that described dielectrophoresis drives, and described program software adopts time period control.
Purpose of the present invention also can realize by following technical measures:
Described chip microprocessor:
This chip microprocessor comprises digital communication interface, logic level transition, chip microprocessor, analog to digital conversion circuit, D/A converting circuit, serial shift register, driving circuit, signal selecting switch, simulation demultiplexer, analog signal conditioner circuit, power expansion circuit, I/V translation circuit, amplifying circuit, photoelectricity isolation and power module.
Link to each other with the serial port of PC by logic level transition, digital communication interface, form two-way data communication;
Link to each other with the input end of two analog signal conditioner circuit arranged side by side respectively by two D/A converting circuits arranged side by side;
Link to each other with the input end of two power expansion circuit arranged side by side respectively by two serial shift registers arranged side by side;
The output terminal that photoelectricity is isolated links to each other with the ADC port of chip microprocessor by I/V translation circuit, simulation demultiplexer;
The output terminal that photoelectricity is isolated links to each other with chip microprocessor by amplifying circuit, simulation demultiplexer, analog to digital conversion circuit;
Chip microprocessor links to each other with the input end of two driving circuits arranged side by side respectively;
Chip microprocessor links to each other with the input end of signal selecting switch;
Described six tunnel high direct voltages:
The control end (CN1-CN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the output terminal of analog signal conditioner circuit respectively;
The output current monitor signal (IN1-IN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end that photoelectricity is isolated respectively;
The output voltage monitor signal (VN1-VN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end that photoelectricity is isolated respectively;
The coil control end (JXC1-JXC6) of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side links to each other with the output terminal of power expansion circuit respectively;
The coil control end (KXC1-KXC6) of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) arranged side by side links to each other with the output terminal of power expansion circuit respectively;
Output "+" end of six high-voltage power modules arranged side by side (D1-D6) is linked in sequence with " normally closed " contact of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6), " often opening " contact of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) respectively, forms electrically driven (operated) six tunnel high direct voltage (V
OUT1-V
OUT6);
" often opening " contact of the output "-" of six high-voltage power modules arranged side by side (D1-D6) end, six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side respectively with " " short circuit;
Described two tunnel micro syringe pump:
Two stepper motors arranged side by side link to each other with the output terminal of two driving circuits arranged side by side respectively; The rotation axis of two stepper motors arranged side by side is linked in sequence with two mechanical push-pull device at fixed arranged side by side, two microsyringes arranged side by side respectively, forms hydraulically powered two tunnel micro syringe pump;
Be connected with the position limitation protection circuit respectively between two mechanical push-pull device at fixed and two driving circuits;
Described two road sine waves:
The input end of two sine wave generating circuits arranged side by side links to each other with the output terminal of signal selecting switch, and the output terminal of two sine wave generating circuits arranged side by side joins with two shaping circuits arranged side by side respectively, forms two road sine waves of dielectrophoresis;
Power module employing ± 15V, ± 5V ,+12V, six tunnel outputs of+5V for module I, II, III, IV provide working power, and provide overcurrent protection for module ii;
Described time period control:
Specimen preparation, sample introduction, mixing in each time period and the micro-fluidic chip biochemical analysis, react, separate, operation steps such as detection is corresponding consistent.
This program software mainly act as: the preset experiment parameter; The independence of controlling six tunnel high direct voltages, two tunnel micro syringe pump, two road sine waves is or/and synchronous output flow process able to programme; The running status of real-time each road high direct voltage of demonstration/record, micro syringe pump, sine wave and output data etc.
In abovementioned technology, the output mode of described six tunnel high direct voltages is " disconnection, voltage/connection, a ground connection ".The output voltage range of described every road high direct voltage is " 0～500V
DC, 0～1000V
DC, 0～2000V
DC, 0～5000V
DC, 0～10000V
DC".
The output mode of described two tunnel micro syringe pump is " preceding wait, propelling/perfusion, then wait for, pull back ".
The linear velocity scope of described propelling (perfusion)/pull back is " 0.05mm/min, 0.5mm/min, 2mm/min, 5mm/min, 10mm/min or 50mm/min ".
Described microsyringe is the glass syringe of " 5 μ l, 10 μ l, 25 μ l, 50 μ l, 100 μ l, 1000 μ l ", and the perfusion volumetric flow rate of micro syringe pump then has program software to convert automatically with reference to the glass syringe specification.
The output mode of described two road sine waves is " wait for preceding wait, sine wave, back ".
Described sine wave freuqency scope is 0～500KHz, and amplitude range is ± 20V.
Described micro-fluidic chip can be quartz, glass, PDMS, PMMA material, and liquid storage tank≤8 have the micro-fluidic chip of all kinds of different structures that deposit tiny array electrode.
The described multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip, with " two road sine waves of electrically driven (operated) six tunnel high direct voltages, hydraulically powered two tunnel micro syringe pump, dielectrophoresis " is an instrument component units, or as required high direct voltage, micro syringe pump, sinusoidal wave output way are expanded or reduced, but basic structure is identical.
Advantage of the present invention:
(1) the present invention has realized the integrated of " micro-fluidic chip analytical approach, electric driving, hydraulic-driven, dielectrophoresis and chip microprocessor control technology ", and a kind of multi-functional micro fluidic device is provided.The combination of multiple drive modes and full automatic control, can replace devices such as the inharmonic high-voltage power supply of many covers, micro syringe pump, dielectrophoresis, measuring instrument, make that the establishment micro-fluidic chip biochemical analysis that adaptability is strong, error range is little is more flexible and easy;
(2) program software of the present invention provides the sequential control environment of a novelty, six tunnel high direct voltages, two tunnel micro syringe pump and two road sine waves in each time period " independence or/and synchronous output able to programme is corresponding fully with the operation steps of micro-fluidic chip biochemical analysis, make the micro-fluidic chip biochemical analysis stride forward major step to keeping a robotization completely;
(3) the invention provides a complete experiment control, six tunnel high direct voltages (disconnect, voltage/connection, ground connection), (the preceding wait of two tunnel micro syringe pump, propelling/perfusion, wait for the back, pull back) and (the preceding wait of two road sine waves, sinusoidal wave, the back wait) combination in any, sequencing control, switch fast and stable output, can realize being connected and nL～pL level biological sample flow (speed) in the microchip channel network of μ L level fluid/biological sample and μ m level passage artificially, driven in synchronism and control that moving phase is formed and flowed to, be convenient to the design of the kinds of experiments manipulation of the different biochemical fluids of realization in the different structure micro-fluidic chip, finish micro-fluidic automatically, microanalysis, especially the specimen preparation in the multi-channel structure micro-fluidic chip biochemical analysis, sample introduction, mix, reaction, operations such as separation;
(4) the invention provides a visual man-machine conversation platform, all operations, show and all in the PC interface, to finish, and interface easy switching, intuitive display are understood.
Description of drawings:
Fig. 1 is the overall construction drawing of the embodiment of the invention;
Among the figure: I is a system control module; II is electric driver module; III is the hydraulic-driven module; IV is the dielectrophoresis module; 1 is PC; 2 is digital communication interface; 3 is logic level transition; 4 is chip microprocessor; 5 is analog to digital conversion circuit; 6,7 is D/A converting circuit; 8,9 is serial shift register; 10,11 is driving circuit; 12 is signal selecting switch; 13,14 are the simulation demultiplexer; 15,16 is the analog signal conditioner circuit; 17,18 is the power expansion circuit; 19 is the I/V translation circuit; 20 is amplifying circuit; 21,22 are the photoelectricity isolation; 23 is power module; 24,26 is spacing holding circuit; 25,27 is stepper motor; 28,29 is sine wave generating circuit; 30,31 is mechanical push-pull device at fixed; 32,33 is shaping circuit; 34,35 is microsyringe.
Fig. 2 is the circuit theory synoptic diagram of the electric driver module of the embodiment of the invention;
Among the figure: D1-D6 is a high-voltage power module; J1-J6 is " single-pole double-throw (SPDT) " high-voltage relay; K1-K6 is " single-pole single-throw (SPST) " high-voltage relay.
Fig. 3 is the mechanical push-pull device at fixed structural representation of the micro syringe pump of the embodiment of the invention.
Among the figure: 36 is the rotation axis of stepper motor; 37 is fixed dam; 38 is limit switch; 39 is the balance guide rail; 40 are the push-and-pull moving slider; 41 is the hydrophobicity medical catheter.
Embodiment:
Embodiment 1:
It is made up of system control module I, electric driver module II, hydraulic-driven module ii I, dielectrophoresis module I V and program software, wherein: described system control module I serves as the control core with chip microprocessor 4, described electric driver module II is six tunnel high direct voltages, described hydraulic-driven module ii I is two tunnel micro syringe pump, described dielectrophoresis module I V is two road sine waves, and described program software adopts time period control.
Described chip microprocessor 4:
Link to each other with the serial port of PC 1 by logic level transition 3, digital communication interface 2; Continuous with the input end of two analog signal conditioner circuit 15,16 arranged side by side respectively by two D/A converting circuits arranged side by side 6,7; Continuous with the input end of two power expansion circuit 17,18 arranged side by side respectively by two serial shift registers arranged side by side 8,9; The output terminal of photoelectricity isolation 21 links to each other with the ADC port of chip microprocessor 4 by I/V translation circuit 19, simulation demultiplexer 13; The output terminal of photoelectricity isolation 22 links to each other with chip microprocessor 4 by amplifying circuit 20, simulation demultiplexer 14, analog to digital conversion circuit 5; Chip microprocessor 4 is continuous with the input end of two driving circuits arranged side by side 10,11 respectively; Chip microprocessor 4 links to each other with the input end of signal selecting switch 12;
Described six tunnel high direct voltages:
The control end (CN1-CN6) of six high-voltage power modules arranged side by side (D1-D6) is continuous with the output terminal of analog signal conditioner circuit 15,16 respectively; The output current monitor signal (IN1-IN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end of photoelectricity isolation 21 respectively; The output voltage monitor signal (VN1-VN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end of photoelectricity isolation 22 respectively; The coil control end (JXC1-JXC6) of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side links to each other with the output terminal of power expansion circuit 17 respectively; The coil control end (KXC1-KXC6) of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) arranged side by side links to each other with the output terminal of power expansion circuit 18 respectively; Output "+" end of six high-voltage power modules arranged side by side (D1-D6) is linked in sequence with " normally closed " contact of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6), " often opening " contact of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) respectively, forms electrically driven (operated) six tunnel high direct voltage (V
OUT1-V
OUT6); " often opening " contact of the output "-" of six high-voltage power modules arranged side by side (D1-D6) end, six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side respectively with " " short circuit;
Described two tunnel micro syringe pump:
Two stepper motors arranged side by side 25,27 are continuous with the output terminal of two driving circuits arranged side by side 10,11 respectively; The rotation axis 36 of two stepper motors arranged side by side 25,27 is linked in sequence with two mechanical push-pull device at fixed arranged side by side 30,31, two microsyringes arranged side by side 34,35 respectively, forms hydraulically powered two tunnel micro syringe pump; Be connected with position limitation protection circuit 24,26 respectively between two mechanical push-pull device at fixed 30,31 and two driving circuits 10,11;
Described two road sine waves:
Two sine wave generating circuits arranged side by side 28,29 input end links to each other with the output terminal of signal selecting switch 12, the output terminal of two sine wave generating circuits arranged side by side 28,29 respectively with two shaping circuits arranged side by side 32,33 join, and form two road sine waves of dielectrophoresis; Power module 23 employing ± 15V, ± 5V ,+12V, six tunnel outputs of+5V for module I, II, III, IV provide working power, and provide overcurrent protection for module ii;
Described time period control:
Specimen preparation, sample introduction, mixing in each time period and the micro-fluidic chip biochemical analysis, react, separate, operation steps such as detection is corresponding consistent.
The output mode of described six tunnel high direct voltages is " disconnection, voltage/connection, a ground connection "; Output voltage range is " 0～500V
DC, 0～1000V
DC, 0～2000V
DC, 0～5000V
DC, 0～10000V
DC"; The output mode of described two tunnel micro syringe pump is " preceding wait, propelling/perfusion, then wait for, pull back "; The linear velocity scope of described propelling (perfusion)/pull back is " 0.05mm/min, 0.5mm/min, 2mm/min, 5mm/min, 10mm/min, 50mm/min "; The output mode of described two road sine waves is " wait for preceding wait, sine wave, back "; Described sine wave freuqency scope is 0～500KHz, and amplitude range is ± 20V; Described micro-fluidic chip can be quartz, glass, PDMS, PMMA material, and liquid storage tank≤8 have the micro-fluidic chip of all kinds of different structures that deposit tiny array electrode; With " two road sine waves of electrically driven (operated) six tunnel high direct voltages, hydraulically powered two tunnel micro syringe pump, dielectrophoresis " is an instrument component units, or as required high direct voltage, micro syringe pump, sinusoidal wave output way are expanded or reduced, but basic structure is identical.
Embodiment 2:
Being connected of each device describes in further detail between 1,2,3 pair of each module of the present invention and in each module in conjunction with the accompanying drawings:
The digital quantity that two 4 tunnel 12 figure place analog conversion circuits 6,7 will be deposited at the preset voltage in the chip microprocessor changes into corresponding 0-+5V
DCAnalog quantity, and send into the analog signal conditioner circuit 15,16 of two 4 passages respectively; 15,16 couples of 0-+5V of two analog signal conditioner circuit
DCAfter analog quantity is nursed one's health, be that six high-voltage power modules (D1-D6) provide control signal, the output voltage preset voltage corresponding with it of six high-voltage power modules (D1-D6) equated; Output "+" end of six high-voltage power modules (D1-D6) is linked in sequence with " normally closed " contact of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6), " often opening " contact of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) respectively, forms electricity and drives the six tunnel high direct voltage (V that handle the biochemical fluid of micro-fluidic chip
OUT1-V
OUT6).
The serial shift register 8 of two 8 passages, 9 will be deposited at the power expansion circuit 17 that the switching value signal that presets six tunnel high direct voltages " disconnection, ground connection " in the chip microprocessor is sent into two 7 passages respectively, 18, two power expansion circuit 17,18 respectively by coil control end JXC1-JXC6, KXC1-KXC6 six " single-pole double-throw (SPDT) " high-voltage relay J1-J6 of control and six " single-pole single-throw (SPST) " high-voltage relay K1-K6, constitute six tunnel high direct voltage (V
OUT1-V
OUT6) " disconnection, voltage/connection, the ground connection " of output mode.
The photoelectricity of two 8 passages isolates 21,22 output current monitor signal IN1-IN6 with six high-voltage power modules (the output current monitor signal is the magnitude of current that is serially connected with the high-voltage power module output loop) and output voltage monitor signal VN1-VN6 (output voltage monitor signal be the output high pressure converted of high-voltage power module proportional low voltage signal by divider resistance) send into the I/V translation circuit 19 of 8 passages and the amplifying circuit 20 of 8 passages respectively, and realize electrical isolation; I/V translation circuit 19 is used for described output current monitor signal is carried out current/voltage-converted, adjustment, and it is sent into the simulation demultiplexer 13 of 8 passages; The simulation demultiplexer 13 of 8 passages is sent the simulating signal of I/V translation circuit 19 output into the ADC port of chip microprocessor, converts it into the corresponding digital quantity signal with output current monitor signal IN1-IN6 by the ADC of chip microprocessor inside.The amplifying circuit 20 of 8 passages is used for amplifying, adjusting described output voltage monitor signal VN1-VN6, and it is sent into the simulation demultiplexer 14 of 8 passages; Simulation demultiplexer 14 is used for the output simulating signal of amplifying circuit 20 is sent into the analog to digital conversion circuit 5 of 8 passages; Analog to digital conversion circuit 5 changes into the corresponding digital quantity signal with voltage monitoring signal VN1-VN6 with this simulating signal, and sends into chip microprocessor.Above-mentioned digital quantity signal shows six tunnel high direct voltage (V by PC at last in real time by the chip microprocessor logical process
OUT1-V
OUT6) output current, voltage.
Two driving circuits 10,11 will be deposited at the output parameter that presets two tunnel micro syringe pump in the chip microprocessor and change into corresponding pulse-modulated signal, and be applied on two stepper motors 25,27, realize Stepping Motor Control; Two mechanical push-pull device at fixed 30, push-and-pull moving slider 40 on 31 is along with stepper motor 25, the rotation of the rotation axis 36 on 27 can be carried out push-and-pull in the horizontal direction and move, and guarantee that by balance guide rail 39 moving of push-and-pull moving slider 40 is stable, push-and-pull moving slider 40 drives two microsyringes 34,35 and the synchronous push-and-pull of hydrophobicity medical catheter 41 inner fluids move, form two tunnel micro syringe pump of the biochemical fluid of hydraulic-driven micro-fluidic chip;
Two position limitation protection circuit 24,26 are that two driving circuits 10,11 provide look-at-me by being installed on the limit switch 38 on the mechanical push-pull device at fixed, constitute the forward and backward position limitation protection of two tunnel micro syringe pump.
Signal selecting switch 12 is used for the PWM pulse-width signal of chip microprocessor is applied to two sine wave generating circuits 28,29; Two sine wave generating circuits 28,29 change into corresponding sine wave with described PWM pulsewidth modulation signal converting respectively, and send into two shaping circuits 32,33 respectively; 32,33 pairs of described sine waves of two shaping circuits carry out shaping, make its output frequency, amplitude equal to preset sinusoidal wave output parameter, form two road sine waves that dielectrophoresis is handled the biochemical fluid of micro-fluidic chip.
23 couples of control module I of power module, electric driver module II, hydraulic-driven module ii I and dielectrophoresis module I V provide working power; Six tunnel high direct voltage (V as electric driver module II
OUT1-V
OUT6) in the monitor value of a certain road output current when surpassing it and presetting the overcurrent protection value, the current foldback circuit in the chip microprocessor control power module 23 can disconnect all working power supply of electric driver module II fast, realizes overcurrent protection.
Embodiment 3: the course of work that the present invention is applied to the micro-fluidic chip biochemical analysis is further described:
Before the experiment, at first according to the structure and the required operation steps of biochemical analysis of micro-fluidic chip, setting experiment parameter (comprising: the output way of high direct voltage, the voltage range of every road high direct voltage, the output way of micro syringe pump, every road micro syringe pump advances linear velocity, the micro-syringe specification of (perfusion)/pull back, sinusoidal wave output way, every road sine wave freuqency, amplitude, the output time hop count, the output mode of each road high direct voltage, each road micro syringe pump, each road sine wave, working time and circulation output number of times etc. in each time period); Secondly will choose sinusoidal wave be connected corresponding of each road high direct voltage, each road micro syringe pump and Ge Lu with micro-fluidic chip.
During the experiment operation, based on the preset experiment parameter, the present invention provides the independence of every road high direct voltage (disconnections, voltage/connections, ground connection) in each period, every road micro syringe pump (preceding wait, propelling/perfusion, then wait for, pull back) and every road sine wave (preceding wait, sine wave, wait afterwards) or/and synchronous output flow process able to programme automatically, thereby can finish operations such as specimen preparation in the micro-fluidic chip biochemical analysis, sample introduction, mixing, reaction, separation in the different structure micro-fluidic chip automatically.
After experiment finishes, preserve set experiment parameter in the complete analysis experiment automatically, so that need not reset during identical experiment.
The above only is the present invention's preferable case study on implementation wherein, is not to be used for limiting practical range of the present invention: promptly all equalizations of being done according to the present patent application claim change and modify, and the scope that is all claim of the present invention contains.
Claims (10)
1. be used for handling automatically the multifunctional microflow control device of the biochemical fluid of micro-fluidic chip, it is characterized in that: it is made up of system control module (I), electric driver module (II), hydraulic-driven module (III), dielectrophoresis module (IV) and program software, wherein:
Described system control module (I) serves as the control core with chip microprocessor (4), described electric driver module (II) is six tunnel high direct voltages, described hydraulic-driven module (III) is two tunnel micro syringe pump, described dielectrophoresis module (IV) is two road sine waves, and described program software adopts time period control.
2. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 1 is characterized in that:
Described chip microprocessor (4):
Link to each other with the serial port of PC (1) by logic level transition (3), digital communication interface (2);
Continuous with the input end of two analog signal conditioner circuit (15,16) arranged side by side respectively by two D/A converting circuits arranged side by side (6,7);
Continuous with the input end of two power expansion circuit (17,18) arranged side by side respectively by two serial shift registers arranged side by side (8,9);
The output terminal that photoelectricity is isolated (21) links to each other with the ADC port of chip microprocessor (4) by I/V translation circuit (19), simulation demultiplexer (13);
The output terminal that photoelectricity is isolated (22) links to each other with chip microprocessor (4) by amplifying circuit (20), simulation demultiplexer (14), analog to digital conversion circuit (5);
Chip microprocessor (4) is continuous with the input end of two driving circuits arranged side by side (10,11) respectively;
Chip microprocessor (4) links to each other with the input end of signal selecting switch (12);
Described six tunnel high direct voltages:
The control end (CN1-CN6) of six high-voltage power modules arranged side by side (D1-D6) is continuous with the output terminal of analog signal conditioner circuit (15,16) respectively;
The output current monitor signal (IN1-IN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end of photoelectricity isolation (21) respectively;
The output voltage monitor signal (VN1-VN6) of six high-voltage power modules arranged side by side (D1-D6) links to each other with the input end of photoelectricity isolation (22) respectively;
The coil control end (JXC1-JXC6) of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side links to each other with the output terminal of power expansion circuit (17) respectively;
The coil control end (KXC1-KXC6) of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) arranged side by side links to each other with the output terminal of power expansion circuit (18) respectively;
Output "+" end of six high-voltage power modules arranged side by side (D1-D6) is linked in sequence with " normally closed " contact of six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6), " often opening " contact of six " single-pole single-throw (SPST) " high-voltage relays (K1-K6) respectively, forms electrically driven (operated) six tunnel high direct voltage (V
OUT1-V
OUT6);
" often opening " contact of the output "-" of six high-voltage power modules arranged side by side (D1-D6) end, six " single-pole double-throw (SPDT) " high-voltage relays (J1-J6) arranged side by side respectively with " " short circuit;
Described two tunnel micro syringe pump:
Two stepper motors arranged side by side (25,27) are continuous with the output terminal of two driving circuits arranged side by side (10,11) respectively; The rotation axis (36) of two stepper motors arranged side by side (25,27) is linked in sequence with two mechanical push-pull device at fixed (30,31) arranged side by side, two microsyringes arranged side by side (34,35) respectively, forms hydraulically powered two tunnel micro syringe pump;
Be connected with position limitation protection circuit (24,26) respectively between two mechanical push-pull device at fixed (30,31) and two driving circuits (10,11);
Described two road sine waves:
Two sine wave generating circuits arranged side by side (28,29) input end links to each other with the output terminal of signal selecting switch (12), the output terminal of two sine wave generating circuits arranged side by side (28,29) respectively with two shaping circuits arranged side by side (32,33) join, form two road sine waves of dielectrophoresis;
Power module (23) employing ± 15V, ± 5V ,+12V, six tunnel outputs of+5V for module I, II, III, IV provide working power, and provide overcurrent protection for module ii;
Described time period control:
Specimen preparation, sample introduction, mixing in each time period and the micro-fluidic chip biochemical analysis, react, separate, operation steps such as detection is corresponding consistent.
3. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 1 and 2 is characterized in that: the output mode of described six tunnel high direct voltages is " disconnection, voltage/connection, ground connection ".
4. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 3, it is characterized in that: described output voltage range is " 0～500V
DC, 0～1000V
DC, 0～2000V
DC, 0～5000V
DC, 0～10000V
DC".
5. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 1 and 2 is characterized in that: the output mode of described two tunnel micro syringe pump is " preceding wait, propelling/perfusion, then wait for, pull back ".
6. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 5 is characterized in that: the linear velocity scope of described propelling (perfusion)/pull back is " 0.05mm/min, 0.5mm/min, 2mm/min, 5mm/min, 10mm/min, 50mm/min ".
7. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 1 and 2 is characterized in that: the output mode of described two road sine waves is " wait for preceding wait, sine wave, back ".
8. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 7, it is characterized in that: described sine wave freuqency scope is 0～500KHz, and amplitude range is ± 20V.
9. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 2, it is characterized in that: described micro-fluidic chip can be quartz, glass, PDMS, PMMA material, liquid storage tank≤8 have the micro-fluidic chip of all kinds of different structures that deposit tiny array electrode.
10. the multifunctional microflow control device that is used for handling automatically the biochemical fluid of micro-fluidic chip according to claim 1, it is characterized in that: with " two road sine waves of electrically driven (operated) six tunnel high direct voltages, hydraulically powered two tunnel micro syringe pump, dielectrophoresis " is an instrument component units, or as required high direct voltage, micro syringe pump, sinusoidal wave output way are expanded or reduced, but basic structure is identical.
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