CN101065187A - Computerized control method and system for microfluidics and computer program product for use therein - Google Patents
Computerized control method and system for microfluidics and computer program product for use therein Download PDFInfo
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- CN101065187A CN101065187A CNA200580040632XA CN200580040632A CN101065187A CN 101065187 A CN101065187 A CN 101065187A CN A200580040632X A CNA200580040632X A CN A200580040632XA CN 200580040632 A CN200580040632 A CN 200580040632A CN 101065187 A CN101065187 A CN 101065187A
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Abstract
Microfluidic devices having active features such as valves, peristaltic pumps, and mixing portions are fabricated to have a thin elastomeric membrane over the active features. The active features are activated by a tactile actuator external to the membrane. A computer executes software for controlling the actuators. The software may include a process manager that executes processes selected by a user from a process library.
Description
The cross reference of related application
The application requires to enjoy the interests of the U.S. Provisional Application sequence number of submitting on September 30th, 2,004 60/614,781.The application is the U. S. application sequence number of submitting on September 8th, 2,005 10/548,652 part continuation application, described U. S. application sequence number 10/548,652 applied for proposing for PCT/US2004/007246 number as PCT on March 10th, 2004, it requires to enjoy in the interests of the U.S. Provisional Application sequence number 60/403,298 that proposed on March 10th, 2003 again.
About the research of federal government's subsidy or the statement of exploitation
The present invention makes under being supported by government, the contract number DAAD19-03-1-0168 that the military authorizes.Government has some right for the present invention.
Background of invention
1. invention field
The present invention relates to be used for computerization control method and the system and the use therein computer program of microfluidic device.
2. background technology
Microfluidic device is a micro device, and it generally includes a plurality of very undersized interconnected microchannels, reservoir and the like etc.The microchannel can have for example width and the height dimension of 10 μ m to 300 μ m usually, but also may be littler and bigger size.Microfluid system generally includes the microfluidic pin actuators of flow (flow) that is used for controlling the microchannel of a lot of independent controls.When the number of described actuator increased, the user of each actuator control was specified the state of each actuator or control along with described user and is become and can not predict.
What need is a kind of system and method, and it is used for the operation of microfluidic device control actuator and therefore flowing in the control channel, thus the operation of control microfluidic device.
Summary of the invention
The present invention can be provided for the improved computerization control method and the system of microfluid, and use therein computer program, and independent control wherein is provided.
Response user input, retrieval process process (process) feature and microfluidic device characteristics.Based on the feature that retrieves, control flow (flow) in the passage of described device.
The feature and advantage of Miao Shuing are not all included in this manual, and especially, consider accompanying drawing, specification and claim, and many supplementary features and advantage will be tangible to those skilled in the art.In addition, it should be noted that the language that uses in this specification mainly is selected for readability and instruction purpose, and not selected in order to narration or restriction theme of the present invention.
The accompanying drawing summary
Fig. 1 is the block diagram of explanation microfluidic device system;
Fig. 2 is the side view of microfluidic device that comprises the tactile actuator of outside, non-integral;
Fig. 3 a to 3c is the cutaway view of Fig. 2 device of 3-3 intercepting along the line, and it comprises the operation of actuator and key diagram 2 devices;
Fig. 4 is the vertical view of microfluidic device, and it comprises and is used to select or controls the tactile actuator that inlet flows and is used for pumping or fluid-mixing;
Fig. 5 is a cutaway view, illustrates that microfluidic channel has side gap to promote the restriction of passage by tactile actuator;
Fig. 6 is the decomposition diagram of multilayer of microfluidic device that comprises the integral body of two kinds of haptic actuation sensor arraies;
Fig. 7 is a perspective view, the microfluidic device that is assembled of key diagram 6;
Fig. 8 is a block diagram, and the software of being carried out by the computer of the microfluidic device system of Fig. 1 is described;
Fig. 9 is a block flow diagram, the operation of key diagram 8 softwares;
Figure 10 is uml class figure, illustrates to be implemented the software software object of encoding that is used for the control microfluidic device;
Figure 11 is the UML sequence chart, and the object information sequence (" control ", " getting ready " and " hardware enclosure device ") in order to control a kind of Braille pin mark (Braille pin) described in Figure 10 is described;
Figure 12 is the UML sequence chart, and the information sequence (" control ", " timing point condition " and " hardware enclosure device ") of object that has two kinds of Braille pin marks of specific time sequence in order to control is described described in Figure 10;
Figure 13 is the UML sequence chart, and the information sequence (" control ", " timing point condition " and " hardware enclosure device ") of object that has two Braille pin marks of specific time sequence in order to control is described described in Figure 10;
Figure 14 is the UML sequence chart, and (" control ", " bonded state " and " attitude is got in timing ready ") in order to the information sequence of the object that activates/deactivate Braille pin mark timing (timing) by the key input from the user is described described in Figure 10;
Figure 15 has illustrated the example of microfluidic device library of the software of Fig. 8;
Figure 16 has illustrated an example in the software processing process storehouse of Fig. 8; And
Figure 17 has illustrated the example of actuator map (map) of the software of Fig. 8.
Detailed description of the preferred embodiments
Description is described embodiment of the present invention, and wherein same reference numerals is represented identical or intimate element.
" embodiment " meaning of quoting in the specification is to comprise special characteristic, structure or the characteristic that described and a plurality of embodiments are relevant at least one embodiment of the present invention.A plurality of local terms " in one embodiment " that occur may not refer to identical embodiment entirely in specification.
Part is subsequently described in detail according to algorithm of operating on the data bit in the computer storage and symbolic representation and is proposed.These arthmetic statements and sign are the methods of giving others skilled in the art in the action of transmitting them most effectively of technical staff's use of technical field of data processing.Algorithm is at this, and usually, is envisioned for step (instruction) sequence of the self-consistentency that causes expected result.Described step needs the physical operations of physical quantity.Although optional, this tittle takes can be stored, transmit, merge, relatively reach electricity, magnetic or the optical signal form of other operation usually.Mainly be owing to normally used reason, sometimes can be easily with these signals as position, value, unit, symbol, character, term, numeral and the like etc.In addition, the step arrangement of physical operations that also can easily some be needed physical quantity sometimes is as module or encoding device, and do not lose generality.
Yet what should be kept firmly in mind is that all these and similar term are relevant with suitable physical quantity, and only is the label easily that is applied to this tittle.Unless expressly stated otherwise,, obvious from following discussion, should understand, the use term that the runs through whole specification for example discussion of " processing " or " computing " or " calculating " or " determining " or " demonstration " or " mensuration " and the like etc. refers to computer system or the similarly operation and the processing of computing electronics, these operations and handle in computer system memory, register or other such information storage, transmission or display unit operation and conversion table is shown the data of physics (electronics) amount.
Some aspect of the present invention comprises that this sentences process steps and instruction that algorithm pattern is described.It should be noted that process steps of the present invention and instruction can be embodied in software, firmware or the hardware, and in the time of in being embodied in software, it is on the different platform of several operation systems use that described step and instruction can be downloaded to be retained in, and operates from described different platform.
The present invention also relates to carry out the device of operation described herein.For required purpose can be constructed this device especially, or described device can comprise the all-purpose computer that the computer program that is stored in the computer optionally activates or reconfigures.Such computer program can be stored in the computer-readable recording medium, dish such as but not limited to any kind comprises floppy disk, CD, CD-ROM, magneto-optic disk, read-only storage (ROM), random-access memory (ram), EPROM, EEPROM, magnetic or optical card, special IC (ASIC), or the medium that is suitable for the store electrons instruction of any kind, and each medium all is connected with computer system bus.In addition, the computer of mentioning in specification can comprise uniprocessor or can be the structure of using the multiprocessor design that strengthens calculated performance.
Algorithm of Ti Chuing and display extrinsic ground relate to any certain computer or other devices herein.Multiple general-purpose system also can be with using according to the program of instruction herein, or it provablely is convenient to construct more specialized device and carries out required method step.The desired structure of multiple these systems will occur in following description.In addition, the present invention does not have to be described with reference to any specific program language.Be understood that multiple program language can be used for realizing as instruction of the present invention described herein, and below provide any reference to language-specific to disclose realization of the present invention and optimal mode.
The invention provides a kind of be used to control, regulate and the detect processing procedure of microfluidic device, the computerized system that flows and operate.Flow with the fluid of controlling microfluidic device by system's control actuator or other device executive softwares, as described flowing in Zhuan Zhi the microchannel.This software can receive user's input from graphic user interface also can automatic operating fluid motion when not having the user to exist.
Fig. 1 is the block diagram of explanation microfluidic device system, is shown in 100 usually.Computer 102 is carried out and is used for by the processing procedure of controller 106 control microfluidic devices 110, the software that flows and operate, and described controller 106 provides control signal and voltage to actuator system or actuator 108.Described controller 106 can pass through USB (USB) and be connected with computer 102.Computer 102 can provide processing procedure, menu mobile and operation to the user, and receive users' selection by user interface 104 by user interface 104.
Described actuator system 108 can be electronically controlled and addressable tactual displays to operate as the active component actuator on microfluidic device 110 (active component actuator).Described actuator system 108 can comprise the Braille unit (as pin mark) with actuator, is used to respond the control signal and the voltage of self-controller 106, and the respective element of engagement microfluidic device 110 is with the fluid treatment process in the control device 110.Described software-controllable system actuator system 108, it is fluid-operated that it transfers control, as: valve control, pumping, mixing and the smudge cells in microfluidic device 110 (cell crushing).Described software can separately be controlled each actuator and control each actuator simultaneously with the control of other actuators 108.Described software can receive user's input and be used for the operation of single actuator or the processing procedure of being carried out by microfluidic device 110.Described software utilizes the processing procedure setting controller 106 of the feature of microfluidic device 110 and actuator system 108 based on customer requirements.Described software can use any object-oriented programming (OOP) language to encode, as: Microsoft's visual c++ environment, maybe can use other program language codings.
The live organism that microfluidic device 110 is suitable in fluid is cultivated.Described microfluidic device 110 is provided by the mobile and composition of the fluid that provides to live organism.Described microfluidic device 110 can provide flowing of layering, that intend multilayer or non-layered.Described microfluidic device 110 can carry out physical operations on live organism.For example, described microfluidic device 110 can be used for general cell to be cultivated, and comprises cell washing and separates, cell inoculation and cultivating.Described microfluidic device 110 can be used as microreactor, tissue culture device, cell culture apparatus, cell sorting device, cell breaking plant, miniature flow cytometer, motile sperm sorter, miniature vaporizer (micro carburetor), microspectrophotometer or minute yardstick tissue engineering devices.Described microfluidic device 110 comprises sensor 112 passing through in order to particulate in the element state of determining microfluidic device 110 or flow performance or the passage.Described sensor 112 can be, for example, and optical pickocff, electric transducer or pickoff.Described microfluidic device 110 can be, for example, the microfluidic device of the title of submitting on March 10th, 2004 for describing among No. 2004/007246, the PCT patent application PCT/US of the integrated microfluidic of sense of touch actuator able to programme " use control " is by intactly incorporating this paper into reference to this patent application.So form microfluidic device described herein described in the PCT application.Described microfluidic device 110 is described hereinafter.
In one embodiment, described microfluidic device 110 comprises the microchannel, and it has the flow performance of active changing and formation in compressible or deformable elastomeric material.In one embodiment, whole microfluidic device 110 is by the elastomeric materials of flexibility, for example: as the organopolysiloxane elastomer of describing hereinafter (" PDMS ").Yet in the part of not expecting movable control (active control), described device substrate also can be by hard material as stiff material structure basically.
Described microfluidic device can contain at least one activity (active) part, and it changes the shape and/or the volume, particularly Zhuan Zhi fluid mobility energy of chamber or path (" region of no pressure ").Such movable part includes but not limited to: mixing portion, pumping part, valve control part, flow part, passage or reservoir are selected part, clasmatosis (cell crushing) part and the part of removing contamination.These movable parts are all exerted pressure by the relevant portion at described device, cause that fluid flows, characteristic of fluid, passage or reservoir feature some change, and therefore change the shape and/or the volume of the region of no pressure that constitutes these parts.Term " region of no pressure " refers to and does not have base material.In use, described region of no pressure is full of fluid or microorganism usually.
Thereby the movable part of described device can be by pressure activation to close their passage or the cross-sectional area of limiting channel ACTIVE CONTROL of realizing expectation separately.For realizing this purpose, described passage, reservoir or other elements are constructed by this way: promptly the pressure from the appropriateness of microfluidic device outside causes described passage, reservoir or other elements (" microfluidic components ") compression and makes the partial restriction or the Close All of parts separately.For realizing this result, wall in the described device plane around the described parts is preferably flexible, and described outer surface is (as: in plane device, outside main surface) be flexible, so that pressure in a small amount can cause outer surface and internal part wall distortion alternatively, thereby or at this some minimizing cross-sectional area or close described parts fully.
By outside haptic device, as be used for the refreshable braille of actuator system 108, be provided for the pressure of the movable part of " activation " described device.Described tactile actuator contacts the movable part of described device 110, and when being excited (energize), described tactile actuator is extended and pushed on deformable elastomer, thereby limits or close the parts in the described movable part.This action can be passed through with reference to figure 2,3a, 3b and 3c explanation.
Fig. 2 has illustrated the microfluidic device 1 that has passage 2 in the substrate 10 of elastomeric material, is elastomeric cap 4 at the top of microfluidic device 1.Contact described lid end face 5 be haptic device 6, described haptic device 6 has the tactile actuator 7 that can extend by means of the application of actuated signal by lead 8,9 downwards.In Fig. 3 a, with along the cross section of line 3-3 as in containing the plane of tactile actuator, having shown the device of Fig. 2.Passage 3 does not get clogged shown in Fig. 3 a, as: as described in tactile actuator (activator) be not excited.
In Fig. 3 b (along the enlarged drawing of the line 3-3 of Fig. 2), described tactile actuator is partly excited, and the result stretches out from described haptic device 6, thereby exerts pressure to the end face 5 of described device, and makes the lid 4 and wall 11 distortion of passage 3.As a result, described channel cross-section is dwindled, and has correspondingly limited mobile.The part of passage 3 is blocked by the projection 12 of the tactile actuator that is excited.In such device, if necessary,, can be only limited to elastomeric cap 4 at the i.e. elastomeric material around herein the passage 3 of described parts.In other words, the wall of the described passage in substrate 10 can be hard, as: micromechanics silica, silicon, glass, duroplasts or metal.Flexible elastic part can be limited to described lid in this embodiment.
In Fig. 3 c, described actuator further (" fully ") is excited, and passage 3 is by retardance (obscured) fully as a result.In this case, tactile actuator is used as open/close valve but not adjustable flow governor.
In the illustrated embodiment, tactile actuator is not to close or limiting part by being excited, but be formed on once the extended position that excites withdrawal or can be applicable to microfluidic device in the excited state, thereby close or limiting channel, and a deexcitation (de-energize) is just further opened passage.
Not only apparatus of the present invention, and working pressure such as air pressure is with other microfluidic devices of active device parts, can obtain obvious improvement on performance with the space that comprises one or more adjacent passages walls by molded described device.These spaces allow each parts to close more completely or be out of shape.Fig. 4 illustrates an example of such structure.In Fig. 4, in the plane of removing elastomeric cap (4 Fig. 2), device is shown from top, provide fluid via " initiatively " service duct 23,24 to passage 20 from supplying with reservoir 21,22.Fluid from passage 20 flows out to outlet reservoir 25.26,27,28,29 and 30 five movable parts are shown in the device.In movable part 27 to 30, each passage (24,20) side and space 27a and 27b, 28a and 28b, 29a and 29b and 30a and 30b join.Movable part 26 sides only join with a space 26a.Dotted line circle in the movable part represents that tactile actuator is excited with restriction or closing passage at these points.
In Fig. 5, passage 24 is shown in the plane vertical with passage length with movable part 27, cover in this case 4 and haptic device 6 and tactile actuator 7 in position.When described actuator 7 during, the wall 27c between passage 27 and its side gap 27a and the 27b, 27d deformable, thereby allow to increase crooked at these movable parts to lower convexity.
Fig. 4 has illustrated that also series connection forms the peristaltic pump of three movable parts such as movable part 28,29 and 30.By activating continuously end to end, can obtain pump action in either direction.By circulating pump action or back and forth, can keep immixture rather than pump action by in a replaceable mode, exciting movable part.
In one embodiment, actuator system 108 is programmable braille display, and it comprises a plurality of movably pin marks, and the corresponding element of each pin mark engagement microfluidic device 110 is to carry out microfluidic procedures.The element of described microfluidic device 110 comprises pump and valve.Described pin mark can be arranged in the geometric array of rule.Such array can use with the different structure of microfluidic device 110.In this configuration, some pin mark is not useable for specific microfluidic device 110, because there is not corresponding this pin mark of element in described device 110.Replacedly, described pin mark can be selected as corresponding element specific or one group of multithread body device 110.Each pin mark can be independently controlled, and for addressable separately.
An example of actuator system 108 is Telesensory systems, as has Gateway
TMThe Navigator of software
TMBraille, it directly translates screen text is the Braille code.These devices generally comprise the linear array of " 8 point " unit, and each unit and each unit " point " respectively are programmable.VI people uses so every style of writing of device conversion, and this is the Braille symbol, and a delegation for example is used for " reading " text message or book.Design described microfluidic device movable part so that they can be positioned on activatable separately " point " or under the projection on the braille.Except other suppliers, braille can be buied from Handy Tech, Blazie and Alva.As what hereinafter will describe, system 100 can use different software procedures to go up performed processing procedure and then carry out the pin mark that processing procedure is controlled actuator system 108 from the storehouse by allowing the user to be chosen in organism.
Yet, be to increase flexibility, the matrix of being convenient to the rule that a plurality of microfluidic devices use may be provided, as have 10 * 10,16 * 16,20 * 100,100 * 100 or other big or small arrays.Described space is tight more and extensible number of protrusions able to programme is many more, and then flexibility is big more in the design of micro device.Building method known in the art is followed in the production of such device.Addressability is also followed conventional method.The array of non-rule also is possible as the pattern that only has actuator in the place of expectation.Activating pin mark can be as United States Patent (USP) 5,842, and using described in 867 incorporated this paper into by reference herein.
Also can construct the device of integrated tactile actuator and described microfluidic device.Described actuator still can be positioned at the outside of described microfluidic device self, but is attached to or is bonded to described microfluidic device to form integrated integral body, as patent the 5th, 580, describes in No. 251, herein by with reference to incorporating this paper into.Also can use the actuator system of other types, as the formation of applied current fluid (referring to United States Patent (USP) the 5th, 496, No. 174) the haptic actuation apparatus, a kind of applying shape memory line with the Braille type device of the electromechanics of replacing between " opening " and " pass " part (referring to United States Patent (USP) the 5th, 718, No. 588), the device of applied current change or magnetorheological working fluid or gel, a kind of pneumatically-operated Braille device is (referring to United States Patent (USP) the 6th, 354, No. 839), " voice coil loudspeaker voice coil " type structure is particularly used " voice coil loudspeaker voice coil " type structure of strong permanent magnetic body, applying shape memory alloy reaches the device of the polymer sheet that conducts in essence (referring to United States Patent (USP) the 5th, 685,721 and 5,766, No. 013), described patent is incorporated this paper into by reference.
Fig. 6 has illustrated an example of whole integrating device, and it comprises nine layers and five subassemblies.This microfluidic device 40 self is cast in the elastomeric individual layer, in this case, corresponding to the thickness of channel height of expectation, for as 30 μ m.Two inlet reservoirs 41 and 42 lead to central passage 45 by access road 43 and 44, and it ends at outlet reservoir 46.Four movable parts have been shown, a movable part is arranged on each access road, it allows the mobile control of each passage 43,44, be included in the interchannel conversion, also shown along two of central passage 45 other movable parts, its can be produced alternatively pulsation with in described passage, mix described fluid stream, crash cells or carry out other processing procedures in described passage.Each movable part of device 40 can be by 48 identifications of the optional side space in the movable part.Extend via the full depth of described device individual layer 40 in reservoir in this embodiment, passage and space.Yet multi-layered devices also is useful.
Can be positioned on device 40 top is subassembly 50, and it comprises hard material, as glass, pottery or hard plastic-substrates 51, and elastic layer 52.Subassembly 50 has three through holes 53,54 and 55, and when described layer was merged, described through hole can communicate with reservoir 42,41 and 46 respectively.Subassembly 50 also comprises four chambeies or hole: 56,57,58 and 59, and it extends via substrate 51 but does not pass through elastic membrane 52.56a is a metallic plate to the inner surface of 59a, to be used as actuator electrode.These electrodes connect by metal forming or trace 59b usually as the common electrical potential source in all chambeies.These chambeies before final assembling, are filled the fluid or the gel of polar organic.
Fig. 7 has illustrated the outward appearance of complete device, and fluid connector 91,92,93 is connected on the cover 61 to impel fluid to be supplied to described reservoir.Oblique pin mark connector at described device rear side is invisible in this figure.As being generally used for integrated circuit, the available thermosetting resin-encapsulated of whole device only allows fluid connector 91,92,93 and electric power connector 71,72 to extend described integrating device.
Fig. 6 and 7 integrating device also can use the separated components manufacturing.In such a case, described actuator assemblies can be used as the unit that separates as subassembly 50,60 and 70,80 and is prepared.In such a case, microfluidic device 40 covers the additional elastic layer of one deck at top and bottom.The use of such nonintegrated structure allows only to reuse the actuator part by changing described microfluidic device layers.
Be suitable for the suitable braille device Graphic WindowProfessional that non-integral is used
TM(GWP) can be from Handy Tech Electronik GmbH, Horb, Germany (Germany) buys, and the braille device has the array of 24 * 16 tactile pins.Also available piezo-activator, as in the device as shown in Fig. 5 and 6, wherein piezoelectric element has replaced ERF, and electrode position is by corresponding change.
Another Application comprises clasmatosis.Can by in passage via movable part transhipment cell and cause pathway closure with the flow through cell of described passage of fragmentation, and smudge cells.Can realize cell detection, for example, by using the low cytometric analysis of transparent microfluidic device and suitable detector.Imbed detection and the activation that optical fiber can promote suitable actuator in the different angles of passage.Similarly detection technique is used in combination the conveying of valve change from passage to each different collection point or reservoir, can be used for choosing embryo and microorganism, comprises bacterium, fungi, algae, yeast, virus and spermatoblast.
Described software control actuator system 108 is with controlled pressure and the therefore opening and closing and the timing of control channel.According to the processing procedure of waiting to hold execution, described software can carry out addressing so that operation to be provided to actuator one by one or by group and by pattern, and described for example being operating as operated or married operation for the peristaltic pump of the fluid in the passage.Described software can be monitored the sensor 112 of microfluidic device 110 so that control channel is mobile selectively.
The software of carrying out by computer 102 is described below.
Fig. 8 is the schematic diagram of explanation by the software of computer 102 and controller 106 execution.Manipulation device driver 802 provides control signal and driving voltage to give actuator system 108 by the process manager 804 of computer 102 manipulations in controller 106 responses.Described process manager 804 comprises by the fluid-operated program (routine) of microfluidic device 110 controls.When processing procedure was required, described process manager 804 was by the processing procedure relevant a series of incidents of device driver 802 control controllers 106 with execution and requirement.Described processing procedure can comprise cell washing or cell separation.A processing procedure can comprise selectable sub-processing procedure, as, cell washing can comprise the sub-processing procedure of using the PBS washing.In another embodiment, described process manager 804 is carried out above-described text editor.In this embodiment, the user can control the processing procedure on the device in the storehouse 110 not, or can add described processing procedure to software.
The information that user interface manager 806 controls and process manager 804 are got in touch, described information receive from the user to user's demonstration and via user interface 104 on user interface 104.Described user can select material and described other fluid-operated features of using in processing procedure, processing procedure timing, the processing procedure.
Actuator map 808 comprises position, function, feature and the operating parameter of the actuator of described actuator system 108.Figure 17 has illustrated an example of actuator map 808.Microfluidic device library 810 comprise passage, valve, pump and other elements of described microfluidic device 110 position, function, feature, interconnect and operating parameter.Described microfluidic device library 810 can comprise the size and dimension of passage, the flow speed characteristic of passage, and it can be depending on fluid type and valve information, as position and flow adjustment feature.Figure 15 has illustrated an example of microfluidic device library 810.Process library 812 can comprise the processing procedure object, and its element and processing procedure feature with described microfluidic device 110 interrelates.For example: the wriggling processing procedure can be corresponding to three valves, and it has the opening and closing of determining order and timing based on size and fluid type.Described process library 812 can comprise the change process process of environment, and it can be used for imitating, and cell is cultivated or the interior cultivation of the body of embryo growth.These processing procedures can be relevant in essence, and can comprise the concentration that changes nutrient, growth factor or vitamin, existence or the disappearance that changes change pH values, change material such as growth inhibitor.Described processing procedure may with flow relevantly, and can comprise flow velocity that fluid is mobile or the variation in the cyclic swing.Figure 16 has illustrated an example of process library 812.
The data from sensor in actuator system 108 (not shown) and the sensor 112 (referring to Fig. 1) in the microfluidic device 110 are handled and stored to detector state module 814.
Illustrative example as the peristaltic pump that forms by three pin mark engagement microfluidic devices 110, a kind of pattern of described process manager 804 repeated application, as XXO, OXX, OOX, XOX, come the fluid in the pumping channels, wherein X is that closing position and O are open positions.The fluid that obtains flows and pulses, and has the instantaneous of both direction and moves.Clean move (net movement) can be by its linear relationship prediction with the patterns of change frequency, and flow direction can be changed by the actuation patterns of reversing.
Fig. 9 is the flow chart of operation of the software of key diagram 8.User interface manager 806 receiving system information and biological information (square 902), and in microfluidic device library 810 and actuator map 808 stored information.Described device information comprises the position and the type of position of components and the type and the actuator in actuator system 108 of microfluidic device 110.User interface manager 806 receives from the user for going up the processing procedure request (as: pumping, mixing, pulverizing or other operations described here) of the processing procedure of carrying out at microfluidic device 110 (square 904).Process manager 804 retrievals are from respective handling process and definite operating parameter of carrying out processing procedure (square 908) of process library 812 (square 906), and described operating parameter is provided to device driver 802.Process manager 804 determines to be used in the processing procedures of the diverse location of microfluidic device 110 based on microfluidic device library 810, and uses actuator map 808 that actuator in the actuator system 108 is related in processing procedure and position.Described device driver 802 produces software object shown in Figure 10 by the process parameters according to above-mentioned retrieval and determines control signal and timing (square 910).Described software object provides control signal and voltage by message shown in Figure 11-14 (square 912) to actuator system 108.Detector state module 814 receives from the situation of microfluidic device 110 and the information of status detection device 112 (square 914).Respond described detector state, process manager 804 is being applied to (square 912) execution FEEDBACK CONTROL (square 916) on the control signal of device.If the user has selected other processing procedures (square 918), the next corresponding object (square 906) of described process manager 804 retrievals also carries out as mentioned above.Otherwise process manager 804 determines whether another user just elect (square 920).If made another selection, user interface manager 806 receives processing procedure request (square 904), and process manager 804 is as above carried out.Otherwise processing procedure finishes (square 922).
In the illustrative example of Fig. 9, each element of software is described to be carried out by computer 102 or controller 106, but also can be carried out by other devices in other embodiments.
In one embodiment, described software is based on the two-dimensional lattice configuration operation of the actuator of actuator system 108.As be used for herein, described corresponding to actuator.Actuator in described matrix makes the elastomer microchannels distortion with configure particular routes and flow velocity.Described software is described based on this configuration, but also can use other configurations.
Figure 10 controls described schematic representation of apparatus for explanation by the software object that process manager 804 produces.The point condition of timing/keying (timed/keyed dot state) object 1002 has defined the point condition of user's selection and the timing that changes in point condition.Key attitude (key state) object 1004 is set quote (reference) for the point by user's input as push button exciting or deactivation (activated or deactivated), and setting is for quoting based on the bonded state of object 1004 and timeline (timeline) object 1006.
The point that described timeline object 1006 is activated or deactivates after playing the clock counter and being illustrated in the specific time cycle.The point that is activated after timing point condition (timed dot state) object 1008 plays the clock counter and is illustrated in specific latent period.Point condition (dot state) object 1010 comprises position and state (as: go up or down) a little and produces the attitude that writes for hardware enclosure device object 1012.Described device driver can use hardware enclosure device (hardware wrapper) object 1012 to carry out.Described hardware enclosure device object 1012 comprises lattice position and the matrix buffer that is used to store the data that are sent to described actuator system 108.
Described process manager 804 is come control hardware by the examples that produce the state machine driver of desired pattern for object 1004 and 1008 in object 1002.Object 1010 carries the information to hardware enclosure object 1012, as each clock cycle (clock cycle), to change the state of described actuator system 108.
Though described the object that Figure 11-14 describes according to one or two point or actuator, can spread to the object that comprises whole actuators or the object of each actuator, this depends on software and implements but be not limited to the present invention.
Figure 11 is the schematic diagram of the sequential of explanation dot state object 1010.Described process manager 804 produces control signal 1101 for dot state object 1010 to set the position and the state (incident 1102) of actuator.Respond described control signal 1101, described dot state object 1010 produces the attitude that writes of hardware enclosure device 1012, and hardware enclosure device 1012 can be the device driver of being carried out by controller 106 802 (incident 1104).Described hardware enclosure device 1012 sends buffered data for actuator system 108, and it comprises the control signal and the voltage (incident 1106) of corresponding pin mark.
Figure 12 is the schematic diagram of the sequential of two timing dot state object of the software of explanation Figure 10.Described process manager 804 is that two timing dot state object 1008A and 1008B produce control signal 1201 to set to the stand-by period of an operation, for the object 1008A of actuator and operation duration and the NextState (incident 1202) of 1008B.Owing to there is the clock signal of self-clock processor, timing dot state object 1008A is that 1012 settings of hardware enclosure device write attitude (incident 1204A) to send data to buffer (incident 1208A and 1208B) and to start timing dot state object 1008B (incident 1206).Described timing dot state object 1008B is that hardware enclosure device 1012 is set and write attitude (incident 1208C and 1208D) and start that timing dot state object 1008A writes attitude (incident 1204B) with setting and be that 1012 settings of hardware enclosure device write attitude (incident 1208E).
Figure 13 is the schematic diagram of the sequential of the key attitude object of the software of explanation Figure 10.Described process manager 804 is that two key attitude object 1004P and 1004S produce control signal 1301, sets the deactivation attitude (deactivation state) (incident 1302) of actuator on the activated state (activation state) of actuator on next key attitude or next the key attitude to be respectively object 1004P and 1004S.The key processor provides the key attitude (incident 1304A) that starts timing point condition 1008 (incidents 1308), and response key attitude object 1004P sets the key attitude object 1004S of response deactivation key attitude.Described key processor provides key attitude (incident 1306) to stop timing point condition 1008 (incident 1308) by key attitude object 1004S for deactivation.
Figure 14 is the schematic diagram of the sequential of the timeline object of the software of explanation Figure 10.Described process manager 804 is that timeline object 1006 produces control signal 1301 with control timing dot state object 1008V and 1008P.Be timing dot state object 1008V and continuous time (incident 1402) of 1008P setting, wherein timeline object processor 1006 service time comes the startup (incident 1402) of state of a control.After the setting duration, activation and the deactivation of timing point condition 1008V and 1008P stops (being respectively incident 1406 and 1408) with the time processor.
The application of the invention can realize numerous functions on single assembly.It is possible using a plurality of reservoirs that are used to supply with nutrient, growth factor and the like etc.Any possibility that is combined into that different reservoirs makes the fluid supply, as: at every turn from single reservoir or from any combination of some reservoirs.As mentioned above, this can finish by setting up with the microchannel of valve control be communicated with the fluid of reservoir.By the actuator system 108 of programming, each independent reservoir can link to each other with growth passage or chamber arbitrarily.Also introduce a plurality of extendible projectioies by supplying with along the microchannel, the wriggling pumping can be carried out by multiple flow velocity.Can produce the effect of Fluid Pulsation of the distinctive injustice of the vertebrate circulatory system easily.In the microfluid cell research, provide a plurality of pumps of bigger flexibility and combination, the adjusting of valve to flow, produce by the micro-actuator grid of use on refreshable braille, and response is waited to implement user's selection of processing procedure and automatically carried out by software.
After reading content of the present invention, those skilled in the art will also be understood that the other interchangeable 26S Proteasome Structure and Function of control fluid-operated system and processing procedure with principle disclosed herein in microfluidic device designs.Therefore, although illustrated and described specific embodiment and application, be understood that and the invention is not restricted to precision architecture disclosed herein and parts, can disclosed herein the inventive method and configuration, operation and the details of device in make improvement, change and the variation that it will be apparent to those skilled in the art, and do not break away from the present invention's spirit and scope as defined by the appended claims.
Claims (26)
1. one kind is used in the mobile method of microfluidic device control, and described method comprises:
Reception is about the user of flowing input desired in described microfluidic device;
In response to described user's input, retrieval process process feature;
In response to described user's input, indexing unit feature; And
Based on the device characteristic and the processing procedure feature of described retrieval, control flowing in the passage of described microfluidic device.
2. method according to claim 1, the step that wherein said control is flowed comprise guides described flowing into place described microfluidic device live organism.
3. method according to claim 1, wherein said microfluidic device is included in the flow valve on the passage in the described microfluidic device, the processing procedure feature of described retrieval comprises the state of a control of described flow valve, and the step that described control is flowed comprises that flowing in described passage produces flowing in response to described user's input to the suitable state of a control of setting described flow valve with restriction and permission.
4. method according to claim 3, the step that wherein said control is flowed comprise that the described flow valve of control produces described the flowing of importing in response to described user with propulsive fluid in described passage.
5. method according to claim 1, the step that wherein said control is flowed comprises:
Shine upon the passage of a plurality of actuators to the described microfluidic device;
Described user's input is associated with described passage; And
In response to described mapping and related step, control described actuator.
6. method according to claim 5, the described step of wherein controlling described actuator comprises the timing of retrieving described actuator status.
7. method according to claim 1 wherein is stored in described processing procedure feature in the process library and with described device characteristic and is stored in the device storehouse.
8. method according to claim 1, it also further comprises generation and described flowing or the relevant feedback signal of described device, wherein said control step is based on described feedback signal.
9. be used for making computer to carry out the computer code of the mobile instruction of control microfluidic device, described code comprises:
Be used in response to importing and the code of retrieval process process feature of being received about the desired user of flowing of described microfluidic device;
Be used for the code of indexing unit feature in response to described user's input; And
Be used for controlling the code that flows of the passage of described microfluidic device based on the device characteristic of described retrieval and processing procedure feature.
10. computer code according to claim 9 wherein saidly is used for controlling mobile code and comprises and be used for described flowing guided into the code of the live organism that places described microfluidic device.
11. computer code according to claim 9, wherein said microfluidic device is included in the flow valve on the passage in the described microfluidic device, the processing procedure feature of described retrieval comprises the state of a control of described flow valve, describedly is used for controlling mobile code and comprises that the suitable state of a control that is used to set described flow valve is with restriction with allow to produce the code that flows in response to described user's input flowing of described passage.
12. computer code according to claim 11 wherein saidly is used for controlling mobile code and comprises and be used to control described flow valve to produce the described mobile code in response to described user's input at described passage propulsive fluid.
13. computer code according to claim 9 wherein saidly is used to control mobile code and comprises:
Be used to shine upon the code of a plurality of actuators to the passage of described microfluidic device;
Be used to make described user to import the code that is associated with described passage; And
In response to described mapping with related and be used to control the code of described actuator.
14. computer code according to claim 11, the wherein said code that is used to control described actuator comprise the code of the timing that is used to retrieve described actuator status.
15. computer code according to claim 9, wherein said processing procedure feature is stored in the process library and described device characteristic is stored in the device storehouse.
16. computer code according to claim 9, the wherein said code that is used for controlling is in response to flowing or feedback signal that described device is relevant and control flowing of described passage with described.
17. one kind is used in the mobile system of microfluidic device control, described system is programmed to:
Reception is about the user of flowing input desired in the described microfluidic device;
In response to described user's input, retrieval process process feature;
In response to described user's input, indexing unit feature; And
Based on the device characteristic and the processing procedure feature of described retrieval, control flowing in the passage of described microfluidic device.
18. system according to claim 17, wherein said system comprise at least one described mobile element of guiding the live organism that places described microfluidic device into.
19. system according to claim 17, wherein said microfluidic device is included in the flow valve on the passage in the described microfluidic device, the processing procedure feature of described retrieval comprises the state of a control of described flow valve, and described system is programmed to the suitable state of a control of setting described flow valve, and flowing in described passage produces flowing in response to described user's input with restriction and permission.
20. system according to claim 19, wherein said system are programmed to the described flow valve of control and produce described the flowing of importing in response to described user with propulsive fluid in described passage.
21. system according to claim 17, wherein said flowing comprises:
Be used to shine upon the equipment of a plurality of actuators to the passage of described microfluidic device;
Be used to make described user's input and described passage associated device; And
Respond described mapping with related and be used to control the equipment of described actuator.
22. system according to claim 21, the wherein said equipment that is used to control described actuator comprises the equipment of the timing that is used to retrieve described actuator status.
23. system according to claim 17, it also comprises the device storehouse that is used to store the process library of described processing procedure feature and is used to store described device characteristic.
24. system according to claim 17, wherein said system comprise the sensor that produces feedback signal with described device or described relevant being used to of flowing, and wherein said system is programmed to and controls mobile based on described feedback signal.
25. one kind is used for controlling a plurality of microfluid actuators and makes the microfluidic device distortion to change in the shape at least one space of described device and/or the method for volume, described method comprises:
Receive and represent the input of flowing desired in described device; And
Produce one group based on the driving signal of processing procedure relevant and device characteristic with described input driving described a plurality of microfluid actuator, and therefore make the described shape in described at least one space and/or stereomutation to obtain described desired flowing.
26. one kind is used for controlling a plurality of microfluid actuators and makes the microfluidic device distortion to change in the shape at least one space of described device and/or the system of volume, described system is programmed to:
Receive and represent the input of flowing desired in described device; And
Produce one group based on the driving signal of processing procedure relevant and device characteristic with described input driving described a plurality of microfluid actuator, and therefore make the described shape in described at least one space and/or stereomutation to obtain described desired flowing.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61478104P | 2004-09-30 | 2004-09-30 | |
| US60/614,781 | 2004-09-30 | ||
| US11/238,696 | 2005-09-29 |
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| CN101065187A true CN101065187A (en) | 2007-10-31 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108463708A (en) * | 2015-11-06 | 2018-08-28 | 密歇根大学董事会 | Microfluid rheometer system based on droplet |
| CN110719888A (en) * | 2017-06-09 | 2020-01-21 | 富士胶片株式会社 | Micro flow path device |
| CN111989153A (en) * | 2018-04-26 | 2020-11-24 | 罗伯特·博世有限公司 | Diluting, mixing and/or aliquoting two liquids in a microfluidic system |
-
2005
- 2005-09-30 CN CNA200580040632XA patent/CN101065187A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108463708A (en) * | 2015-11-06 | 2018-08-28 | 密歇根大学董事会 | Microfluid rheometer system based on droplet |
| US11879820B2 (en) | 2015-11-06 | 2024-01-23 | Regents Of The University Of Michigan | Droplet-based microfluidic rheometer system |
| CN110719888A (en) * | 2017-06-09 | 2020-01-21 | 富士胶片株式会社 | Micro flow path device |
| CN110719888B (en) * | 2017-06-09 | 2023-10-03 | 富士胶片株式会社 | Micro flow path device |
| CN111989153A (en) * | 2018-04-26 | 2020-11-24 | 罗伯特·博世有限公司 | Diluting, mixing and/or aliquoting two liquids in a microfluidic system |
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