CN101458519A - Travelling wave dielectrophoresis separating chip control and acquisition system and implementing method thereof - Google Patents

Abstract

The invention relates to the micro-electronic-mechanical-system (MEMS) technique field, in particularly the micro-fluidic chip control and feeble signal collecting field. A travelling wave dielectrophoresis discrete chip control and collect system is composed of a biology inverted microscope, a travelling wave dielectrophoresis discrete chip, a host control PC machine and a slave controller. The host control PC machine realizes data communication with the slave machine which has characteristic that the host control PC machine includes a micro-digital image processing and analysing module; NIOSII soft core processor in the slave controller is used as a center control processor for controlling data communication between the host and slave machines, controlling output of four-stage DDS module, controlling DMA staring collocation of CMOS image sensor and controlling corresponding peripheral. The system has merits that design cost is reduced, system robustness is increased, factitious design error is reduced by using SOPC technique.

Description

Row ripple dielectrophoresis separating chips control and acquisition system and its implementation

Technical field

The present invention relates to micro electro mechanical system (MEMS) technology (MEMS) field, particularly the control of micro-fluidic chip and feeble signal are gathered the field.

Background technology

At present, the dielectrophoresis chip technology is as a kind of important biochip technology, analyzes fast because of it has, amount of samples is few, highly sensitive, have Noninvasive, be easy to integrated and advantage such as robotization, has obtained people's common concern in recent years.Difference by electrode structure can be divided into the dielectrophoresis chip three major types type: conventional dielectrophoresis chip, row ripple dielectrophoresis chip, electrorotation chip.Its cardinal principle is: in inhomogeneous field, biologic grain can be by electric field polarization, and the biologic grain that different structure and material are formed has the principle of different responses, reach to they control, carry, purpose such as separation.Yet, conventional dielectrophoresis separating chips is generally according to the difference of the dielectric properties of different biologic grains (as cell), adopt forward dielectric power and negative sense dielectric power to realize controlling and separate to biologic grain (as cell), for example the research group of Cheng J utilizes forward dielectric power, negative sense dielectric power to realize (the Nature Biotechnolo-gy that separates of active yeast cell and dead yeast cells, 1998 (16), PP:541-546).Adopt forward dielectric power and negative sense dielectric power, require the dielectric diversity ratio of two kinds of separated cells bigger, just can reach reasonable separating effect.Simultaneously, in experimentation,, can't realize the continuous separation of cell owing to remove extra electric field.And when cell is subjected to forward dielectric power to be adsorbed to electrode edge, because electrode edge is the place of electric field intensity maximum often, too high electric field intensity (1000V/m) tends to pair cell and damages, and is serious even can make cell membrane puncture cell rupture.Require robotization, integrated characteristics in order to overcome the problem that conventional dielectrophoresis exists in separating and to agree with micro-full analytical system, proposed based on programmable system on the sheet (System On Programmable Chip, SOPC) technology realization row ripple dielectrophoresis chip controls and Acquisition System Design scheme.

Summary of the invention

The objective of the invention is at row ripple electrophoresis chip control features and a kind of system architecture of designing flexibly, upgrading easily, control mode is convenient, it is low in energy consumption, highly sensitive to have, be easy to produce in batches and control, acquisition system and its implementation of cheap capable ripple dielectrophoresis separating chips.

The present invention is achieved through the following technical solutions: realize the control and the collection of row ripple dielectrophoresis separating chips based on the SOPC technology.The capable ripple dielectrophoresis separating chips that the control of this row ripple dielectrophoresis separating chips and acquisition system are prepared from by indium tin oxide target (ITO) and dimethyl silicone polymer (PDMS), CMOS MT9T001 imageing sensor, biological inverted microscope and photography extend neck, upper control PC and following level controller etc. are formed.Upper control PC is realized the functions such as control, microscopic digital Flame Image Process and electrophoretic analysis of slave computer.Following level controller is to be embedded in NIOSII soft-core processor among the FPGA as central control processor, data communication between the control upper and lower machine, control separating chips drive signal module---be embedded in the output of four phase place DDS modules among the FPGA, the initial configuration of control cmos image sensor and the control of relevant peripheral hardware.

Dielectrophoresis separating chips control of the present invention's row ripple and acquisition system, in FPGA EP2C35 chip, customize special-purpose lower computer system by SOPC Builder, this lower computer system module is made up of NIOSII soft-core processor, four phase place DDS modules, sdram controller, USB controller, Flash controller, lcd controller, keyboard input controller and high speed image data acquisition controller, and wherein the DDS IP kernel generates in Matlab/Simulink by DSPBuilder; Lcd controller and high speed image data acquisition controller adopt the User Defined logic realization.

The control of the present invention's row ripple dielectrophoresis separating chips with its workflow of acquisition system is: biomone potpourri to be separated is earlier by behind the sample injection, control four phase place DDS modules by the NIOSII soft-core processor and export the sine wave signal that four tunnel phase place strictnesses differ 90 °, make and produce row ripple electric field in the little raceway groove of capable ripple dielectrophoresis separating chips, biomone is subjected to the traction of dielectrophoresis force to do directional migration along specific separation raceway groove, because of different biomone dielectric property differences, thereby present different migration rates, after cmos image sensor MT9T001 gathers the biology microscope image, under based on the acquisition controller effect of Avalon stream mode, the biology microscope image that collects is saved among the SDRAM, and after after certain Flame Image Process, by the USB2.0 interface biology microscope image that collects is passed in the PC at last, carry out follow-up biology microscope Flame Image Process and electrophoretic analysis etc.

The technical program is encapsulated into the system core module among the single FPGA EP2C35 by the SOPC technology, constitutes a kind of capable ripple dielectrophoresis separating chips control and acquisition system of novelty, realizes the quick separation of biologic grain.Its useful effect mainly shows utilizes the SOPC technology to reduce design cost, and special-purpose DDS chip price is higher, and function is more, usually can not utilize repertoire during application, causes the wasting of resources, and design cost improves.Be embedded into to use in the system and can't make design cost what increase and this method for designing will design based on the DDS circuit, and the value that only need change the data bits N of phase control words, frequency control word, amplitude control word and look-up table gets final product, control convenient; Utilize the SOPC technology, realization is to the data acquisition of cmos image sensor, NIOSII and acquisition controller are placed on among a slice FPGA, can solve after generally hardware design is finished, as selecting more high-performance hardware processor for use, cause problems such as system power and cost waste, can solve and adopt traditional design method systemic-function upgrading difficulty, problem such as the dirigibility of maintainability difference and design is lower; Effectively the structure of simplified system, shorten from notion to the distance that realizes.Simultaneously, adopt the NiosII soft-core processor can improve the robustness of system, reduce the factor that artificial design is slipped up.

Description of drawings

The present invention is further described below in conjunction with drawings and Examples.

The capable ripple dielectrophoresis of Fig. 1 separating chips processing process figure;

Control of the capable ripple dielectrophoresis of Fig. 2 separating chips and acquisition system schematic diagram

Fig. 3 DDS basic structure schematic diagram;

Fig. 4 is based on the synoptic diagram of DDS subsystem in Matlab/Simulink of DSP Builder;

Fig. 5 is based on Avalon stream mode CMOS acquisition controller interface;

Fig. 6 realizes the software flow pattern of four phase place DDS control;

Fig. 7 realizes MT9T001 acquisition software process flow diagram.

Embodiment

Below in conjunction with accompanying drawing technical scheme of the present invention is further described.

Figure 1 shows that the processing technology of capable ripple dielectrophoresis separating chips, it mainly comprises two parts: the one, and the preparation of row ripple dielectrophoresis separating chips ITO electrod-array, adopt the MEMS processing technology in the preparation process, adopt methods such as photoetching, wet etching to prepare array ITO electrode; The one, PDMS separates the preparation of little raceway groove, adopt Protel software to draw the shape of row ripple dielectrophoresis separating chips raceway groove, utilize the circuit board making technology to process mould, adopt the PDMS integral pouring procedure to prepare the little raceway groove of PDMS chip, and realize the overall package of chip through the oxygen plasma bonding techniques.

Figure 2 shows that capable ripple dielectrophoresis separating chips control and acquisition system schematic diagram, comprise upper control PC, following level controller, capable ripple dielectrophoresis separating chips, CMOS MT9T001 imageing sensor, four phase place DDS output modules and four road DAC0832 and the compositions such as LPF circuit, biological inverted microscope and photography extend neck, LCD demonstration and micro-injection sample introduction control circuit that wherein descend level controller to comprise that FPGA EP2C35, SDRAM, USB2.0 control chip, ITO and PDMS are prepared from.Wherein micro-injection sample introduction circuit is made up of control damping fluid sample introduction and potpourri sample introduction circuit to be separated; In FPGA EP2C35 chip, customize special-purpose lower computer system by SOPC Builder, this system module is made up of NIOSII soft-core processor, four phase place DDS modules, sdram controller, USB controller, Flash controller, lcd controller, keyboard input controller and high speed image data acquisition controller, and wherein the DDS IP kernel generates in Matlab/Simulink by DSP Builder; Lcd controller and high speed image data acquisition controller adopt the User Defined logic realization.Biomone potpourri to be separated is earlier by behind the sample injection, control four phase place DDS modules by the NIOSII soft-core processor and export the sine wave signal that four tunnel phase place strictnesses differ 90 °, make and produce row ripple electric field in the little raceway groove of capable ripple dielectrophoresis separating chips, biomone is subjected to the traction of dielectrophoresis force to do directional migration along specific separation raceway groove, because of different biomone dielectric property differences, thereby present different migration rates, after cmos image sensor MT9T001 gathers the biology microscope image, under based on the acquisition controller effect of Avalon stream mode, the biology microscope image that collects is saved among the SDRAM, and after after certain Flame Image Process, by the USB2.0 interface biology microscope image that collects is passed in the PC at last, carry out follow-up biology microscope graphical analysis and processing.

Fig. 3 is the structure principle chart of DDS, and it produces frequency, phase place and the controlled sine wave of amplitude in the mode of digital controlled oscillator.Circuit has comprised phase accumulator, phase-modulator, compositions such as (surplus) string ROM look-up table, reference clock source, DAC just.Wherein former three is the numerical portion in the DDS structure, has the function of numerical control frequency synthesis.The core of DDS system is a phase accumulator, finishes phase-accumulated process.Under the control of reference clock, frequency control word is added up by phase accumulator, to obtain the respective phase data, the phase place output of phase-modulator receiving phase totalizer, be mainly used in the phase modulation (PM) of signal, the data of its output are come just (surplus) string ROM look-up table of addressing as sampling address, finish the phase-magnitude conversion, export different amplitude codings; After the amplitude modulator modulation, obtain corresponding sine wave through DAC again; , can obtain sine wave by the continuous transformation output of frequency, phase place and the decision of amplitude control word after low-pass filter offset of sinusoidal ripple carries out smoothing processing.

Fig. 4 is the synoptic diagram of DDS subsystem in Matlab/Simulink based on DSP Builder, ultimate principle according to DDS, utilize the DSP developing instrument DSP Builder of FPGA that DDS has been carried out modeling, build application model based on four phase place sinusoidal signal generators of DDS technology.Based on the DDS subsystem of DSP Builder, it has 3 inputs, is respectively Freqword (32 bit frequency control word), Phaseword (16 phase control words), Amp (10 amplitude control words); An output, i.e. 8 DDSOut outputs; 2 Parallel Adder Subtractor are respectively phase accumulator and phase-modulator, and LUT is sinusoidal ROM look-up table.Matlab/Simulink compiles the DDS system that has designed, and by calling " Signal Compiler " instrument of DSPBuilder, being correlated with is provided with and this design can be converted to VHDL language, thereby generates the DDS IP kernel in quartusII.During design, call 4 DDS subsystems in QuartusII, utilize SOPC Builder to make up after the NIOSII system, under NIOSII control, promptly may command is exported four phase place sine wave signals.In the system, for simplify procedures design and strict guarantee output four mutually sine wave successively phase differential be 90 °, with the LPM_RAM Block formation LUT look-up table of 4 1K, depositing phase differential respectively is 90 ° of constant amplitude sinusoid tabular values in FPGA.

Fig. 5 is based on Avalon stream mode CMOS acquisition controller interface, select the cmos image sensor MT9T001 of 3,000,000 pixels (2048 * 1536) of Micron Inc. for use, it has the advantage of high sensitivity, high output frame rate, low noise, low-power consumption, high dynamic range.MT9T001 provides the two-wire serial bus interface, can control the gain of sensor electronics, pixel integration time, exposure sensor time, output image size, output image position and image output frame rate by the setting value that changes the sensor internal register.In the system, if each collection is all realized the collection of data by NIOSII processor adopting inquiry mode, the speed of collection is quite slow.In order to realize the high speed acquisition of data, adopt the Avalon stream mode to realize the collection of data.

Fig. 6 with the main line that is operating as of response keyboard, carries out corresponding task according to the response of keyboard for realizing the software flow pattern of four phase place DDS control.Its course of work is that after system start-up, system at first enters the parameter setting state, by initial signal frequency, phase place and the amplitude size of keyboard input.Display screen shows the corresponding setting state in the process that is provided with.After configuring original state, NIOSII handles accordingly according to setting value, be converted into frequency control word, phase control words and amplitude control word then and deliver to four phase place DDS modules, the DDS module is exported corresponding Wave data to DAC0832 according to the parameter of input, exports the sinusoidal signal drive controlling dielectrophoresis microchip that four tunnel phase place strictnesses differ 90 ° through LPF.

Fig. 7 is for realizing MT9T001 acquisition software process flow diagram, at first the MT9T001 imageing sensor is realized configuration, whether correctly by writing control word to corresponding registers, whether the control word that relatively writes register then is consistent with the control word of readout register, determine MT9T001 configuration.Whether the start frame of judging piece image then arrives, as after capturing initial frame head, just starts a DMA and transmit a frame image data, just continues the corresponding DMA control program of response as continuous acquisition, otherwise with regard to EOP (end of program).

Control, acquisition system and its implementation of the present invention's design can be widely used in the microfluidic analysis chip Biologic grain is controlled, is carried and separation etc., have control signal produce convenient, processing speed fast, sensitivity High, chip is easy to batch production and the advantage such as cheap. Simultaneously, can solve the traditional system side of employing Genealogy of law system function upgrading difficulty, the problem such as the flexibility of maintainability difference and design is lower can be widely used in facing The fields such as bed medical science, environmental monitoring, legal medical expert's criminal investigation.

Claims (7)

1, a kind of capable ripple dielectrophoresis separating chips control and acquisition system based on the SOPC technology, be made up of biological inverted microscope, row ripple dielectrophoresis separating chips, host computer PC and following level controller etc., host computer PC is by the data communication of USB2.0 realization with slave computer.The functions such as control, microscopic digital Flame Image Process and electrophoretic analysis that it is characterized in that upper PC realization slave computer; The NIOSII soft-core processor is as central control processor in the following level controller, and the startup of the data communication between the control upper and lower machine, the output of control four phase place DDS modules, control cmos image sensor is disposed and the relevant peripheral hardware of control.

2, capable ripple dielectrophoresis separating chips control according to claim 1 and acquisition system is characterized in that the setting of frequency control word, phase control words and amplitude control word that described controlled variable is provided with module and comprises four phase place DDS modules and the setting of CMOS MT9T001 imageing sensor parameter.

3, capable ripple dielectrophoresis separating chips control according to claim 2 and acquisition system is characterized in that the startup configuration and the collection of described CMOS MT9T001 imageing sensor, adopt from customizing I ²The C module realizes the configuration to MT9T001, and realizes the collection of high speed micro-image data based on the Avalon stream mode.

4, capable ripple dielectrophoresis separating chips control according to claim 1 and acquisition system, it is characterized in that described four phase place DDS modules export the sine wave that four tunnel phase place strictnesses differ 90 ° and be used to control the required dielectric power amplitude of capable ripple dielectrophoresis chip biological separate particles, phase place etc., and drive biomone and in the little raceway groove of specific chip, realize travel motion.

5, capable ripple dielectrophoresis separating chips control according to claim 1 and acquisition system, it is characterized in that described capable ripple dielectrophoresis separating chips, adopt PDMS to make the specific little raceway groove of chip and transparent ITO electro-conductive glass as electrode material, and finally make ITO microelectrode array and PDMS microfluid pipeline be encapsulated into one through the oxonium ion bonding, realize the preparation of row ripple dielectrophoresis separating chips.

6, capable ripple dielectrophoresis separating chips control according to claim 1 and acquisition system is characterized in that described biological inverted microscope, and separating effect in the little raceway groove of chip is amplified, and strengthen and detect effect, improve the discrimination of Flame Image Process.

7, capable ripple dielectrophoresis separating chips control according to claim 1 and acquisition system is characterized in that described relevant peripheral hardware control, adopt from customizing the peripheral hardware instruction mode, realize the driving of LCD, Keyboard, USB2.0 control chip etc.

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