EP1972375A1 - Mikrofluidikvorrichtung auf der Basis von Aktivmatrixprinzipien - Google Patents

Mikrofluidikvorrichtung auf der Basis von Aktivmatrixprinzipien Download PDF

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Publication number
EP1972375A1
EP1972375A1 EP07104773A EP07104773A EP1972375A1 EP 1972375 A1 EP1972375 A1 EP 1972375A1 EP 07104773 A EP07104773 A EP 07104773A EP 07104773 A EP07104773 A EP 07104773A EP 1972375 A1 EP1972375 A1 EP 1972375A1
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EP
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Prior art keywords
micro
fluidic device
flexible substrate
components
active matrix
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EP07104773A
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French (fr)
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Koninklijke Philips NV
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Koninklijke Philips Electronics NV
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater

Definitions

  • the present invention is related to a micro-fluidic device including a two-dimensional array of a plurality of components for processing a fluid and/or for sensing properties of the fluid.
  • Micro-fluidic devices are at the heart of most biochip technologies, being used for both the preparation of fluidic samples and their subsequent analysis.
  • the samples may e.g. be blood based.
  • the sample solution may comprise any number of things, including, but not limited to, bodily fluids like blood, urine, serum, lymph, saliva, anal and vaginal secretions, perspiration and semen of virtually any organism: Mammalian samples are preferred and human samples are particularly preferred; environmental samples (e.g. air, agricultural, water and soil samples); biological warfare agent samples; research samples (i.e.
  • the sample may be the products of an amplification reaction, including both target an signal amplification); purified samples, such as purified genomic DNA, RNA, proteins etc.; unpurified samples and samples containing (parts of) cells, bacteria, virusses, parasites or funghi.
  • Biochip or “Lab-on-a-Chip” or alike, refer to systems, comprising at least one micro-fluidic component or biosensor, that regulate, transport, mix and store minute quantities of fluids to rapidly and reliably carry out desired physical, chemical and biochemical reactions in larger numbers.
  • These devices offer the possibility of human health assessment, genetic screening and pathogen detection.
  • these devices have many other applications for manipulation and/or analysis of non-biological samples. Biochip devices are already being used to carry out a sequence of tasks, e.g. cell lyses, material extraction, washing, sample amplification, analysis etc.
  • micro-fluidic devices and biochips already contain a multiplicity of components, the number of which will only increase as the devices become more effective and more versatile.
  • Suitable properties that can be sensed or modified include, but are not limited to, temperature; flow rate or velocity; pressure, fluid, sample or analyte presence or absence, concentration, amount, mobility, or distribution; an optical characteristic; a magnetic characteristic; an electrical characteristic; electric field strength, disposition, or polarity.
  • the analysis system consists of a (disposable) cartridge (e.g. biochip, lab-on-a-chip, microfluidic device or alike system) comprising a biochemical processing module and a bench-top machine.
  • a (disposable) cartridge e.g. biochip, lab-on-a-chip, microfluidic device or alike system
  • the components for temperature control as well as analysis e.g. light source, CCD camera, etc.
  • the bench-top machine can only be used for a particular design or a selective number of cartridge designs. Consequently, the performance of various assays requires nowadays a plurality of bench-top machines.
  • US patent 6,852,287 proposes embodiments of a method to control a number N of independently controllable components with smaller number of control terminals.
  • both the use of multiplexing techniques or passive matrix techniques is proposed.
  • the matrix technique is extremely attractive, as this allows for the maximum number of components to be controlled with the minimum number of control terminals.
  • one specific heater element is activated also a number of other heater elements will be activated unintentionally.
  • This object is achieved by a micro-fluidic device, e.g. a biochip, fabricated on a substrate based upon active matrix principles.
  • the device is preferably fabricated from one of the well known large area electronics technologies, such as a-Si, LTPS or organic transistor technologies.
  • the active matrix makes it possible to independently control a larger number of components on the device with a smaller number of control terminals.
  • This use may require a flexible cartridge which is not fragile, which can be made in any desired shape and in some cases may be easily disposed of by e.g. incineration.
  • the present invention relates to a micro-fluidic device (1) comprising a two-dimensional array of a plurality of components (2) for processing a fluid and/or for sensing properties of the fluid, wherein the components comprise at least one heater element, and wherein each component (2) is coupled to at least one control terminal (9, 10) enabling an active matrix to change the state of each component individually, and wherein the active matrix includes a two-dimensional array of electronic components realized in thin film technology on a flexible substrate.
  • the flexible substrate allows the device to be made in a variety of three dimensional shapes.
  • the flexible substrate is advantageous for fitting a cartridge based on this device in a diagnostic platform where a sample is further analyzed.
  • the flexible substrate comprises a plastic or metal foil, even more preferred the flexible substrate essentially consists of plastic.
  • the substrate comprises parylene or polyamide.
  • the active matrix includes a two-dimensional array of electronic components realized in thin film technology.
  • the active matrix provides a high versatility of the device.
  • the thin film technology ensures a very cost efficient manufacturing also of large devices.
  • the flexible substrate comprises only plastic substrates.
  • the cartridge may be easily disposed of by e.g. incineration.
  • At least one of the flexible substrates may be punctured by a needle or other device present in e.g. the reading device. This may be facilitated if the flexible substrate is made thin, or is made of a material which has mechanical properties which encourage puncture, such as a low shear strength. In this manner, it is possible to introduce the sample to be analyzed or other reagents into the device by puncturing the thin flexible substrate. In this manner, no holes need to be fabricated in the substrate to allow fluids to enter or leave the cartridge. More preferably, the thin flexible substrate may be made from an elastic material, whereby the substrate will re-seal after the sample or reagent have been introduced. In this manner no additional valves or taps will be required to confine a fluid in a closed system (as opposed to a flow through system) in the cartridge.
  • the device comprises at least two, even more preferred a multiplicity of heater elements.
  • a thermal processing array Such a device is referred to as a thermal processing array.
  • These heater elements are suitable for heating fluid that may be present in cells or compartments of the microfluidic device.
  • the thermal processing array can be used to either maintain a constant temperature across the entire compartment area, or alternatively to create a defined time-dependent temperature profile if the reaction compartment is also configured in the form of an array and different portions of the reaction chamber require different temperatures.
  • the thermal processing array comprises a multiplicity of individually addressable and drivable heating elements, and may preferably comprise additional elements such as temperature sensors and fluid-mixing or fluid-pumping elements or a combination thereof.
  • the device comprises a multiplicity of temperature sensors to control a pre-defined temperature profile across an array of components or cells. This embodiment is illustrated in Fig. 4 .
  • the components for heating, and the other optional components are all present on a biochemical processing module, which is preferably located in a biochip, lab-on-a-chip, microfluidic device, or alike system.
  • the micro-fluidic device is preferably a disposable unit, which may be a replaceable part of a larger disposable or non-disposable unit (e.g. lab-on-a-chip, genechips, microfluidic device, or alike system).
  • the device may optionally comprise cells or cavities that can hold a fluid. Such cells are also referred to as array elements.
  • the electronic components of the active matrix are formed by thin film transistors having gate, source and drain electrodes.
  • the active matrix includes a set of select lines and a set of control lines such that each individual component is controlled by one select line and one control line and the gate electrode of each thin film transistor is connected to a select line.
  • a memory device for storing a control signal supplied to the control terminal.
  • the electronic components are formed by thin film diodes, e.g. metal-insulator-metal (MIM) diodes. It is preferred that a MIM diode connects a first electrode of each component to a control line, and a second electrode of each component is connected to a select line.
  • MIM diodes connects a first electrode of each component to a control line, and a second electrode of each component is connected to a select line.
  • the thin film diodes are PIN or Schottky diodes, wherein a first diode connects a first electrode of each component to a control line, wherein a second diode connects the first electrode of each component to a common rest line and wherein a second electrode of each component is connected to a select line.
  • the first diode is replaced by a pair of diodes connected in parallel and the second diode as well is replaced by a pair of diodes connected in parallel.
  • the first diode is replaced by a pair of diodes connected in series, and also the second diode is replaced by a pair of diodes connected in series.
  • the invention relates to a method for the manufacturing of a micro-fluidic device according to the invention, comprising:
  • the rigid substrate is preferably selected from glass, Silicon or other semiconductor wafer, Mica, metal plate etc.
  • the method in a preferred embodiment further comprises forming a release layer between the plastic substrate and the rigid carrier substrate.
  • the release layer suitably comprises amorphous silicon.
  • Fig. 1 illustrates the general concept of a micro-fluidic device based on an active matrix.
  • the micro-fluidic device as a whole is designated with the reference number 1.
  • the device comprises a two-dimensional array of components 2.
  • Each component 2 is associated with a switching means 3 arranged to selectively activate the component 2.
  • Each switching means is connected to a control line 4 and a select line 6.
  • the control lines 4 are connected to a common control driver 7.
  • the select lines 6 are connected to a common select driver 8.
  • the control lines 4 in conjunction with the select lines 6 form a two-dimensional array of control terminals 9, 10.
  • the component 2 may be any electronic device e.g. a heater element, a pumping element, a valve, a sensing component etc. being driven by either a voltage or a current signal. It is to be understood that the examples for the components 2 are not to be construed in a limiting sense. Activating a component 2 means changing its state e.g. by turning it from on to off, or vice versa or by changing its setting. It is also noted that the individual switching means 3 may comprise a plurality of sub components comprising both active and/or passive electronic components. However, there is no requirement that all sub components are activated together.
  • micro-fluidic device 1 illustrated in Fig. 1 to independently control a single component 2 is as follows:
  • the respective select line 6 is unselected, returning all switching means 3 into a non-conducting state, preventing any further change in the state of the preselected component.
  • the device will then remain in the non-addressed state until the following control signal requires to change the state of any one of the components 2, at which point the above sequence of operation is repeated.
  • the two-dimensional array formed by the control lines 4 and the select lines 6 can also be described in terms of rows and columns, where the select lines 6 define the rows and the control lines 4 the columns.
  • micro-fluidic device 1 it is also possible to address the micro-fluidic device 1 such that a component 2 is only activated while the control signal is present.
  • a memory device into the component whereby the control signal is remembered after the select period is completed.
  • the memory device a capacitor or a transistor based memory element is suitable. This makes it possible to have a multiplicity of components at any point across the array activated simultaneously. This option is not available in the passive system known in the prior art. Of course, if a memory device is available, a second control signal will explicitly be required to de-activate the component.
  • the device comprises cells and channels, most preferred microfluidic channels, that connect one cell to at least one, or more preferred a plurality of, other cells.
  • a valve is located between the cells. This enables the performance of a reaction with various steps in the device.
  • fluids may be moved sequentially from one cell to another or alternatively many cells may be processed in parallel.
  • Fig. 2 shows the construction of a fluidic channel that can be heated via active matrix electronics, based on a flexible plastic substrate.
  • the device in Fig. 2 shows a plastic backing plate 18, a plastic layer with a fluidic channel 19, and a thin film transistor 20.
  • 21 refers to a flexible film.
  • the flexible substrate comprises a plastic backing plate, a plastic layer comprising microfluid channels and a flexible film layer adhered to the active matrix components.
  • the flexible film is supported by a second backing plate.
  • the flexible film comprises parylene, polyimide or a combination thereof.
  • the device of Fig. 2 is modified such that the fluid channel may be heated from two sides. This would require the inclusion of contact vias.
  • a metal layer is included on the plastic backing plate or top plate for enabling electrical contact.
  • Fig. 3 illustrates a preferred embodiment, wherein heating from both sides of a fluid channel is possible.
  • the device thus further comprises a top electrode 22, a via 23 and a plastic top plate 24.
  • the plastic substrate (backing plate, top plate respectively) may be any suitable plastic.
  • the plastic is selected from colorless polymides, polyethylene naphtalate, polyethersulfone, benzocyclobutene or a combination thereof.
  • the thickness of the flexible film will generally be between 0.01 to 50 micrometers, preferably from 50 nm to 1 micrometer.
  • the plastic layer having embedded therein the microfluid channels preferably has a thickness of from 10 to 1000 micrometer, more preferred from 50 to 500 micrometer.
  • the plastic backing plate preferably has a thickness of from 100 to 2000 micrometer.
  • Fig. 3A illustrates a preferred embodiment of the device.
  • the thin flexible film makes it possible that a needle 25 or other device present in e.g. the reading device may puncture the capsule. This may be facilitated if the flexible substrate is made of a material which has mechanical properties which encourage puncture, such as a low shear strength.
  • a sample to be analyzed or other reagents may be introduced into the device by puncturing the thin flexible substrate. In this manner, no holes need to be fabricated in the substrate to allow fluids to enter or leave the cartridge.
  • the thin flexible substrate may be made from an elastic material, whereby the substrate will re-seal after the sample or reagent have been introduced and the needle retracted. In this manner no additional valves or taps will be required to confine a fluid in a closed system (as opposed to a flow through system) in the cartridge.
  • the invention relates to a method for the manufacturing of a micro-fluidic device according to the invention, comprising:
  • the two dimensional array of components is formed on a thin film flexible substrate.
  • This substrate is subsequently released from the rigid carrier and combined with a plastic backing plate and a plastic layer with fluidic channels (referred to as the fluidics layer) to arrive at a device as shown in Fig. 2 .
  • the fluidics layer and backing plate are built up over the two dimensional array of components and release only takes place subsequently.
  • a further second substrate arrangement is manufactured on top of the two dimensional array of components, either as a step-wise manufacturing process or by adhering pre-manufactured modules comprising a combination of a backing plate and fluidics layer.
  • the resulting device comprises an array of components sandwiched between a plastic backing plate, a fluidics layer and a plastic top plate. Such a device is illustrated in Fig. 3 .
  • the device according to the invention on a flexible substrate, such as making the structures directly onto freestanding plastic substrates, transfer processes and sacrificial etching, it is highly preferred that the method as described herein in more detail is used.
  • the claimed process essentially allows thin film transistors to be fabricated on flexible, preferably plastic, layers, interconnects to be made and some packaging to be carried out while the flexible substrate is still connected to the glass. The release is carried out after the components have been formed.
  • the flexible substrate essentially consists of plastic.
  • the plastic is capable of wet casting.
  • the plastic layer can for example be applied to the rigid substrate by a spin-on process. Alternatively the plastic can be applied by spreading with a blade or printing techniques.
  • Release of the flexible substrate may be enabled by the use of a release layer. If a release layer is used it may comprise amorphous silicon and release may be obtained with a laser process. It is preferred that the release layer comprises amorphous silicon.
  • the invention enables accurate, reproducible, reliable and fast thermal cycling during DNA amplification on a biochip, for instance using (multiplexed) PCR or (multiplexed) real-time quantitative PCR (RQ-PCR), such that the temperature of the array elements may be individually and in parallel controlled, without significant additional costs or issues concerning the number of input and output pins.
  • RQ-PCR real-time quantitative PCR
  • the invention relates to use of the device according to the invention in a process wherein temperature is controlled.
  • the invention relates to use of the device according to the invention in a process wherein the temperature is changed according to a pre-defined regime.
  • this invention allows an advantageous way of performing RQ-PCR on a biochip by combining a cost-effective high performance thermal processing array (e.g. high resolution, individual and parallel temperature control of compartments, high reproducibility, high reliability and high accuracy) on the disposable, with the high performance (e.g. high resolution, high signal-to-noise ratio) of an optical detection setup (e.g. light source, CCD camera, filters) generally used in a bench-top machine for detection of fluorescent signals in molecular diagnostics.
  • a cost-effective high performance thermal processing array e.g. high resolution, individual and parallel temperature control of compartments, high reproducibility, high reliability and high accuracy
  • an optical detection setup e.g. light source, CCD camera, filters
  • the invention relates to a method of performing the PCR process, preferably RQ-PCR process wherein use is made of the micro-fluidic device as described above.
  • the invention relates to the microfluidic device as described above, in combination with an optical detection set up.
  • the invention relates to a method of detecting a product using a diagnostic device comprising a micro-fluidic device according to the invention, wherein the detection is based on optical methods.
  • Fig. 4 exhibits an active matrix micro-fluidic device 1 using thin film transistors (TFT) 12 as switching means 3 to ensure that all components, for example the heating elements, can independently be activated.
  • TFT thin film transistors
  • Each component 2 is connected to the matrix of control terminals via a TFT switch 12.
  • At least one of the components is a heater element.
  • TFTs are well known switching elements in thin film large area electronics, and have found extensive use e.g. in flat panel display applications. Industrially, the major manufacturing methods for TFTs are based upon either amorphous-silicon (a-Si) or low temperature polycrystalline silicon (LTPS) technologies. But other technologies such as organic semiconductors or other non-Si based semiconductor technologies, such as CdSe, can be used.
  • a-Si amorphous-silicon
  • LTPS low temperature polycrystalline silicon
  • CdSe non-Si based semiconductor technologies
  • the device will then remain in the non-addressed state until the following control signal requires to change the state of any one of the components, at which point the above sequence of operation is repeated.
  • TFT based switch With a TFT based switch, it is again possible to control more than one component in a given row simultaneously by applying a control signal to more than one column in the array during the select period. It is possible to sequentially control components in different rows by activating another row by using the select driver and by applying a control signal to one or more columns in the array. Furthermore, it is still possible to address the system such that the component is only activated while the control signal is present, or alternatively to incorporate a memory device into the component (e.g. a capacitor element, or a transistor based memory element) whereby the control signal is remembered after the select period is completed.
  • a memory device e.g. a capacitor element, or a transistor based memory element
  • the heater elements are provided as a regular array of identical units, whereby the heaters are connected to the driver via the switches (e.g. transistors) of the active matrix.
  • the gates of the transistors are connected to a select driver (for example a standard shift register gate driver as used for an AMLCD), whilst the source is connected to the heater driver, for example a set of voltage or current drivers. Operation is as follows:
  • the biochemical processing module comprises a discrete array of heating elements 13 based on active matrix principles, such that a reaction compartment 14 contains a plurality of heaters.
  • a reaction compartment 14 contains a plurality of heaters.
  • biochemical processing module There are several options for configuring the biochemical processing module depending upon the required heat processing.
  • a driver Whilst in this embodiment of Fig. 5 a driver is considered which is capable of providing (if required) signals to all columns of the array simultaneously, it is also feasible to consider a more simple driver with a function of a de-multiplexer. In this example only a single output driver is required to generate the heating signals (e.g. a voltage or a current). The function of the de-multiplex circuit is simply to route the heater signal to one of the columns, whereby only the heater is activated in the selected line in that column. It should be understood that a plurality of drivers with a function of a de-multiplexer may be used to drive the entire heater array.
  • an integrated heater driver is included per heating elements based on active matrix technology.
  • the device comprises a local driver provided with a memory function. This allows the heating signal to be applied for a longer period of time, enabling better and more accurate control of a given temperature profile.
  • the device comprises a multiplicity of temperature sensors to control a pre-defined temperature profile across an array of components or cells. This embodiment is illustrated in Fig. 6 .
  • the biochemical processing module comprises a compartment 14 or a plurality (e.g. array) of compartments 14 and a discrete array of heating elements (13) and the at least one temperature sensor (T).
  • Each heating element is individually drivable, whereby a multiplicity of temperature profiles may be created.
  • the temperature profile can advantageously be measured by a plurality of temperature sensors.
  • the temperature sensors may be used to prevent a temperature from extending beyond a given range, and may preferably be used to define and control the desired temperature profile.
  • the device comprises a compartment or plurality (e.g. array) of compartments (cells) and a discrete array of heating elements and at least one mixing or pumping element.
  • Each heating element is individually drivable, whereby a multiplicity of temperature profiles may be created.
  • a uniform temperature profile can advantageously be created by a plurality of mixing or pumping elements.
  • the mixing or pumping elements are integrated into the heating element array, for example if this component were to be manufactured using large area thin film electronics technologies, such as low temperature Poly-Si.
  • cooling is provided by a (bench-top) machine handling a PCR module, for instance by bringing the PCR module in thermal contact with a cooled mass, peltier element, etc., or by use of convection (e.g. fan).
  • a cooling element is incorporated in the PCR module, such as a thin-film peltier element, or an array of cooling elements is incorporated.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP07104773A 2007-03-23 2007-03-23 Mikrofluidikvorrichtung auf der Basis von Aktivmatrixprinzipien Ceased EP1972375A1 (de)

Priority Applications (1)

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EP07104773A EP1972375A1 (de) 2007-03-23 2007-03-23 Mikrofluidikvorrichtung auf der Basis von Aktivmatrixprinzipien

Applications Claiming Priority (1)

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EP07104773A EP1972375A1 (de) 2007-03-23 2007-03-23 Mikrofluidikvorrichtung auf der Basis von Aktivmatrixprinzipien

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KR20100122534A (ko) * 2009-05-13 2010-11-23 한국과학기술원 플렉서블 바이오센서, 이의 제조 및 사용방법
WO2019100575A1 (zh) * 2017-11-22 2019-05-31 南方科技大学 数字微流控液滴驱动装置及驱动方法

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US6403367B1 (en) * 1994-07-07 2002-06-11 Nanogen, Inc. Integrated portable biological detection system
EP1686626A2 (de) * 1998-02-25 2006-08-02 Seiko Epson Corporation Verfahren um ein Dünnschicht-Bauelement zu trennen, verfahren um ein Dünnschicht-Bauelement zu transferieren, Dünnschicht-Bauelement, aktives Matrix-Substrat, und Flüssigkristallanzeige
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100122534A (ko) * 2009-05-13 2010-11-23 한국과학기술원 플렉서블 바이오센서, 이의 제조 및 사용방법
WO2019100575A1 (zh) * 2017-11-22 2019-05-31 南方科技大学 数字微流控液滴驱动装置及驱动方法

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