JP5969132B2 - Digital microfluidic system with swappable board - Google Patents

Description

  The present invention relates to a digital microfluidic system or apparatus capable of inserting one or more disposable cartridges for manipulating a sample in a droplet. A digital microfluidics system controls the selection of an electrode array supported by a substrate and the individual electrodes of this electrode array and provides a central voltage supply to the individual electrodes for individual voltage pulses for manipulating droplets by electrowetting. And a control unit. Thus, the present invention also relates to a droplet actuator device that facilitates molecular technology of droplet operation. The art is generally related to the control and manipulation of small amounts of liquid, usually in microscale or nanoscale form.

  Automatic liquid handling systems such as the robotic workstation Freedom EVO® by the present applicant (Tecan Schweiz AG, Zecher-8708 Mennedorf, Seestraße 103, Switzerland) are known in the art. well known. This device allows automatic liquid handling in a separate instrument or automatically in conjunction with the analysis system. These automated systems are not designed to be portable and typically require large volumes of liquid (microliters to milliliters) for processing. In digital microfluidics, individual droplets are addressed (electrowetting) when a predetermined voltage is applied to the electrodes of the electrode array. A general overview of electrowetting methods can be found in Vol. 34, No. 4 of the Transactions on Industry Applications of the American Institute of Electrical and Electronics Engineers (IEEE), published by Shantou in 1998, and by Paulac (2002) Pollack et al., Lab chip, Vol. 2, P96-101. Briefly, electrowetting is a method of moving droplets using a microelectrode array that is preferably covered by a hydrophobic layer. Application of a predetermined voltage to the electrodes of the electrode array causes a change in the surface tension of the droplets present on the addressed electrodes. This significantly changes the contact angle of the droplet on the addressed electrode and thus moves the droplet. In performing such an electrowetting procedure, two main methods for placing the electrodes are known, using a single surface with an electrode array to induce droplet movement, or , Adding a second surface with similar electrodes opposite and having at least one ground electrode. The main advantage of the electrowetting technique is that it requires only a small drop, for example one drop. Therefore, the liquid treatment can be executed in a very short time. Furthermore, the movement control of the liquid can be performed completely under electronic control, with the result that the sample is processed automatically.

  An apparatus for manipulating droplets by electrowetting (single planar arrangement of electrodes) using one face with an electrode array is known from US Pat. No. 5,486,337. All the electrodes are arranged on the surface of the carrier substrate, arranged below the carrier substrate or covered by a non-wetting surface. The voltage source is connected to the electrode. A droplet is moved by applying a voltage to the next electrode, and thus applying a voltage continuously to the electrode induces the movement of the droplet above the electrode.

  An electrowetting device that controls droplet movement on a microscale using an electrode array having an opposing surface with at least one ground electrode is known from US Pat. No. 6,565,727 (two-plane arrangement of electrodes). Each surface of the device may comprise a plurality of electrodes. Two opposing arrays form a gap. The surface of the electrode array facing the gap is preferably covered with an electrically insulating hydrophobic layer. The liquid droplets are arranged in the gap, and move in the filler having no polarity by continuously applying a plurality of electric fields to the plurality of electrodes arranged on the opposite side of the gap.

  A container of polymer film for manipulating the sample in the droplet is known from WO 2010/069977 A1. The biological sample processing system includes a large volume processing vessel, a flat polymer film on the lower surface, and a hydrophobic upper surface. The flat polymer film is maintained at a distance from the underside of the container by the protrusions. This distance defines at least one gap when the container is placed on the film. The droplet manipulation instrument comprises at least one electrode array that guides the movement of the droplet. Also, a substrate supporting at least one electrode array is disclosed with a control unit of a droplet manipulation instrument. The container and film are reversibly attached to the droplet manipulation instrument. Thus, the system allows movement of at least one droplet from the at least one well through the channel of the container onto the hydrophobic top surface of the flat polymer film and above the at least one electrode array. By means of a droplet manipulation instrument, the above-described droplets on the hydrophobic top surface of a flat polymer film are guided by electrowetting to control movement where biological samples are processed.

  For the processing of biological samples, the use of such electrowetting devices for manipulating droplets is known from WO 2011/002957 A2. Among them, a droplet actuator typically includes a lower substrate having a control electrode (electrowetting electrode) insulated by a dielectric, a conductive upper substrate, and a hydrophobic coating on the lower substrate and the upper substrate. Contains. Also disclosed is a droplet actuator device that replaces one or more elements of a droplet actuator, a disposable element. From this international application, a droplet actuator is known which has a fixed (eg PCB) lower substrate, an electrowetting electrode and a removable or replaceable upper substrate. The self-contained cartridge includes, for example, a buffer, a reagent, and a filler. The pouch in the cartridge is used as a fluid reservoir and may be perforated to release fluid into the cartridge gap. The cartridge includes a ground electrode that is replaced with a hydrophobic layer and is open to guide the sample into the gap of the cartridge. The cartridge may be adhered to the electrode by an interface material (eg, liquid, adhesive, or grease).

  A microfluidic processing or analytical disposable cartridge in an automated system for performing molecular diagnostic analysis is disclosed in WO 2006 / 125767A1 (see US Patent Application Publication No. 2009 / 0298059A1 for an English translation). The cartridge is configured as a flat chamber device (having the size of a check card) and can be inserted into the system. Samples can be dispensed into cartridges through ports.

  It is an object of the present invention to propose an alternative digital microfluidic system or digital microfluidic device that is configured to contain one or more disposable cartridges for manipulating an internal droplet sample. is there. This object is therefore achieved by proposing a digital microfluidic system for manipulating a sample in a droplet in a disposable cartridge. Such a disposable cartridge preferably includes a lower layer, an upper layer, and a gap between the lower layer and the upper layer.

The digital microfluidic system according to the present invention is:
(A) a base unit having at least one cartridge housing configured to place a disposable cartridge;
(B) at least one electrode array supported by the lower substrate, extending substantially in a first plane and having a plurality of individual electrodes;
(C) A central control unit that controls the selection of the individual electrodes of the at least one electrode array and supplies the individual electrodes with individual voltage pulses for manipulating droplets in the cartridge by electrowetting. With.

  The digital microfluidics system according to the present invention further includes at least one substrate housing portion disposed in one of the cartridge housing portions of the base unit. Each substrate accommodating portion is configured to place an exchangeable electrode plate including an electrode array and a plurality of electrical substrate contact elements electrically connected to the individual electrodes of the electrode array. Each substrate housing portion includes a plurality of electrical base unit contact elements that are electrically connected to the central control unit, and the electrical base unit contact elements are electrically connected to the exchangeable electrode plate disposed in the substrate housing portion. It is configured to engage or fit with the substrate contact element.

  Preferably, the at least one substrate housing portion is disposed below one of the cartridge housing portions of the base unit, and is configured to mount an exchangeable electrode plate inserted into the base unit of the digital microfluidic system. ing. Another preferred embodiment of the digital microfluidic system according to the present invention is here disclosed as well.

  Preferably, the digital microfluidic system is configured to contain one or more disposable cartridges that can be inserted into the base unit of the digital microfluidic system. More preferably, the digital microfluidic system comprises at least one disposable cartridge that manipulates the sample in the droplet using the digital microfluidic system or apparatus thereof. More preferably, the lower layer and the upper layer of the cartridge have a hydrophobic surface exposed in the gap between the cartridges, and the cartridge does not have a conductive layer.

  Preferably, the digital microfluidic system includes at least one cover plate having an upper substrate, and the at least one cover plate is disposed in the cartridge housing portion. The at least one cover plate further comprises a conductive member, which extends in the second plane substantially parallel to the electrode array of the cartridge receptacle to which the at least one cover plate is assigned. The conductive member of the at least one cover plate is not connected to the potential source. Preferably, the conductive member of the cover plate is a conductive foil attached to the cartridge.

  According to the first preferred modification of the cartridge housing portion, the cover plate is configured to be movable with respect to the electrode array of each cartridge housing portion. According to a second preferred variant, the cartridge housing part is movable in a direction substantially parallel to the electrode array of each cartridge housing part so as to house a disposable cartridge which is slid and inserted. It is configured.

  Preferably, the digital microfluidic system has at least one interchangeable electrode plate having an electrode array supported by a lower substrate and having a plurality of electrical substrate contact elements electrically connected to individual electrodes of the electrode array. Is provided.

  Another object of the present invention is to provide an alternative digital microfluidic system to perform different analyzes in a disposable cartridge for manipulating a sample in a droplet using a digital microfluidic system or apparatus thereof. It is to propose a means to technically adopt the system. This further object is achieved by proposing at least one interchangeable electrode plate that is configured to be arranged in a substrate housing of a digital microfluidic system. At least one exchangeable electrode plate includes an electrode array supported by the lower substrate and a plurality of electrical substrate contact elements electrically connected to the individual electrodes of the electrode array. At least one interchangeable electrode plate is configured to be disposed in one of the above-described substrate accommodation portions of the digital microfluidic system. The electrical board contact element is configured to be engaged with or fitted to the electrical base unit contact element of the base unit that is electrically connected to the central control unit of the digital microfluidic system.

  Preferably, the lower substrate supporting the electrode array is configured as a printed circuit board (PCB), and the electric circuit board contact elements are arranged in the vicinity of the end of one or more printed circuit boards. Preferably, the individual electrodes of the electrode array are arranged and configured to manipulate droplets within the cartridge by electrowetting and to perform specific analyses. Particularly preferably, at least one electrode array of the exchangeable electrode plate is covered by a dielectric layer.

  Yet another object of the present invention is to propose an alternative method for manipulating a sample in a droplet in a digital microfluidic system or apparatus thereof. This further object is achieved by proposing a method for manipulating a sample of droplets adhering to a hydrophobic surface.

The first method according to the present invention comprises the following steps:
(A) preparing a digital microfluidic system according to the present invention;
(B) Prepare the cartridge described here,
(C) preparing the exchangeable electrode plate described here,
The replaceable electrode plate includes an electrode array that is configured to perform a specific analysis within the gap of the cartridge, and during the analysis, the sample in the droplets adhering to the hydrophobic surface is within the gap by electrowetting. Operated.

The second method according to the present invention comprises the following steps:
(A) Prepare the digital microfluidics system described here,
(B) Prepare the cartridge described here,
(C) Select the exchangeable electrode plate according to the present invention,
The replaceable electrode plate includes an electrode array that is configured to perform a specific analysis within the gap of the cartridge, and during the analysis, the sample in the droplets adhering to the hydrophobic surface is within the gap by electrowetting. Operated.

  Additional inventive features and preferred embodiments and variations of the digital microfluidics system, the exchangeable electrode plate, and the method of droplet sample manipulation are described in the specification and the dependent claims.

  The present invention includes the following advantages.

• Providing interchangeable electrode plates makes the digital microfluidics system very flexible for different analyzes that can be performed on disposable cartridges. This is because each interchangeable electrode plate is specifically designed to perform one specific analysis. Thus, by providing a very simple interchangeable electrode plate at an affordable price, it is possible to avoid designing the electrode array to be complex and expensive to serve many purposes.

-Instruments with interchangeable electrode plates are more flexible and less expensive than designing disposable digital microfluidic cartridges with integrated PCBs. By placing certain features of the analysis on a replaceable PCB rather than in a disposable cartridge, a simpler cartridge that is comprehensive for multiple analyzes can be utilized. Both improved simplicity (by removing the PCB) and the ability to manufacture many cartridges (by being comprehensive for use in many different analyzes) allow for low cost manufacturing.

● Replaceable electrode plates that are damaged or no longer function can be easily replaced without the use of special tools or specialist maintenance.

● Provide future digital analysis using the same digital microfluidics system by providing a digital microfluidics system that has at least a substrate housing for mounting the exchangeable electrode plate. Open up the possibility to do.

Covering at least one electrode array of the exchangeable electrode plate with a dielectric layer further protects the photosensitive surface of the electrode array from oxidation and fingerprints.

The disposable cartridge may be configured as a mere consumable for performing a predetermined analysis for each exchangeable electrode plate by providing a gap between the working layer and the working layer. The working layer of the cartridge prevents contamination of the interchangeable electrode plate and the entire digital microfluidic system.

The concept of “exchangeable PCB” is that expensive components remain in the instrument, common to many biochemical analyses. For example, a digital microfluidics system comprises:
O Exchangeable PCBs designed for analysis of specific groups (eg in molecular biology), eg with:
○ Upper layer with electrode pattern that defines analysis capacity ○ Second layer with trace wiring to supply power to each electrode ○ Third layer with thin trace that applies heat to specific region ○ Measure temperature of specific region 4th layer with integrated thermocouple for control ○ Board that connects all layers and their electrical contacts ● High voltage power relay module for controlling on / off switching of PCB electrode When,
● Power supply for supplying power to the entire system ● Optical module (for example for fluorescence detection) ● Clamp and / or vacuum module to hold the cartridge in place on the PCB ● To the bottom of the PCB and on the PCB A magnetic actuator that moves the permanent magnet away from the bottom (the permanent magnet generates a stronger magnetic field than the electromagnet)
● Analog / digital input / output module for controlling digital output (ie, magnetic actuator, heater, vacuum, etc.) and input (thermocouple, etc.) ● Power module for supplying power to the system ● Running system with: Embedded processor ○ Software and user interface

  In accordance with the present invention, a digital microfluidics system is proposed as an “instrument platform” that can be used for almost all biochemical applications, including all of the expensive bulleted bullet items listed above. ing. By changing or changing only the open bullet items, a “different instrument” or “new instrument” may be formed to run a completely different application.

  This concept has two important advantages.

  1. Manufacturers should produce each of a number of instrument platforms or digital microfluidics systems (ie, see the bulleted item above) because of the large number of them at a significant cost reduction. Adding selected change items for a given number of instrument platforms in stock (ie see the selection of bulleted items above) creates many types of digital microfluidic systems, each with a specific application Dedicated. Replacing the selected change item (ie select the bulleted item above) on an already produced instrument platform results in a new digital microfluidic system of a different type, each dedicated to a new application It is.

  2. A user may purchase a single instrument platform dedicated to a particular application (eg, an instrument for measuring a particular analyte in a blood sample). If the user decides to perform a different experiment or analysis, the user becomes a new digital microfluidic system dedicated to each new item (ie selection of bulleted items above). Simply replace it with something. For example, to perform an ELISA analysis, the PCB may be replaceable and the software may be updated so that the instrument becomes an immunoassay system.

  In both of these cases, the digital microfluidic system may be designed such that the software is actually included in the chip on the PCB so that the software is automatically updated when the PCB is replaced.

  In accordance with the present invention, a digital microfluidics system has been proposed as a multi-level “instrument platform”. At the first level, the base unit of the digital microfluidic system is similar for all applications that utilize electrowetting technology. Thus, a comprehensive instrument is formed and expensive, but with a high degree of flexibility by allowing common modules to remain in the instrument base unit and replaceable parts such as insertable PCBs and insertable cartridges. Is brought about. At the second level, the PCB is a replaceable element that can be replaced by the manufacturer or end user. Since the replaced PCB electrode array interfaces to the base unit at the contacts, the movement of the droplets within the cartridge located on the top of the PCB is precisely controlled. The contacts on the PCB and in the base unit are preferably standardized. At the third level, different types of cartridges incorporated with different sets of reagents are available. The same type of cartridge may be used for the same analysis, but different samples may be introduced.

  The selection of the digital microfluidic system, replaceable electrode plate, self-contained disposable cartridge, and sample handling method of the present invention, with the help of the accompanying schematic diagram illustrating selected exemplary embodiments, It has been described without narrowing the scope and spirit of the invention.

1 is a schematic view of a digital microfluidic system including a central control unit and a base unit, four cartridge accommodating portions, and four substrate accommodating portions for accommodating interchangeable electrode plates each having an electrode array. The electrode array is arrange | positioned at the fixed lower board | substrate, and sectional drawing of one cartridge accommodating part which has the disposable cartridge of 1st Embodiment described here. Sectional drawing of one cartridge accommodating part which has the disposable cartridge of 2nd Embodiment described here by which the electrode array is arrange | positioned at the fixed lower board | substrate. A digital microfluidic system comprising a central control unit and a base unit, twelve cartridge accommodating portions each having a fixed cover plate, and twelve substrate accommodating portions accommodating interchangeable electrode plates each having an electrode array Overview view. One cartridge housing with a disposable cartridge of the third embodiment described herein showing a top-insertable cartridge inserted into a substantially vertical cartridge housing having a substantially vertical electrode array and a cover plate Sectional drawing of a part. Sectional drawing of the one cartridge accommodating part which has the disposable cartridge of 3rd Embodiment accommodated here which shows the upper insertion type cartridge seen from the cut surface B shown by FIG. 5A. The lower substrate of this interchangeable electrode plate is a printed circuit board (PCB), and is an overview of the interchangeable electrode plate that can be inserted into a digital microfluidic system. The electrode array is a detailed cross-sectional view of FIG. 2 arranged on the interchangeable electrode plate of the first embodiment in electrical contact. FIG. 4 is a detailed cross-sectional view of FIG. 3 in which the electrode array is disposed on the exchangeable electrode plate of the second embodiment in electrical contact. Schematic of a comprehensive multi-level “instrument platform” with a standardized base unit with all common modules and further comprising a replaceable PCB and a replaceable cartridge suitable for a particular experiment or analysis.

  FIG. 1 shows an overview of an exemplary microfluidic system 1 comprising a central control unit 14 and a base unit 7, four cartridge housings 8 each having an electrode array 9, and a cover plate 12. It is. The digital microfluidics system 1 manipulates a sample in a droplet 23 in a disposable cartridge 2 comprising a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4. It is configured as follows. Accordingly, the sample in the droplet 23 is operated in the gap 6 of the disposable cartridge 2. In addition, the digital microfluidic system 1 of the present invention includes four substrate housing portions 40 for housing the exchangeable electrode plate 41.

  The digital microfluidics system 1 includes a base unit 7 having at least one cartridge housing portion 8 configured to place a disposable cartridge 2 thereon. The digital microfluidics system 1 may be a stand-alone and non-portable unit, and a plurality of operators bring their own cartridges 2 to work. Therefore, the digital microfluidics system 1 may include a plurality of cartridge housing portions 8 and a plurality of electrode arrays 9, and at least a part of the electrode arrays 9 is disposed on the exchangeable electrode plate 41. A plurality of cartridges 2 can work simultaneously and / or in parallel. The number of cartridge accommodating portions 8 and substrate accommodating portions 40 may be one or any number between 1 and 100, for example. This number is limited, for example, by the working capacity of the central control unit 14.

  Since it is preferable to integrate the digital microfluidics system 1 with a fluid handling workstation or a Freedom EVO® robotic workstation, a pipette robot can receive a portion of the liquid and / or a sample containing the liquid. Can be used to move to and from the cartridge 2. Instead, the digital microfluidic system 1 includes only a small number of, for example, one disposable cartridge 2 and may be configured as a portable terminal that can cooperate with the cartridge 2. Those skilled in the art will appreciate that methods between the two extremes described above also operate and operate within the spirit of the invention.

  According to the present invention, the digital microfluidic system 1 also has at least one for mounting a replaceable electrode plate 41 comprising an electrode array 9 which extends substantially in the first plane and has a plurality of individual electrodes 10. Two substrate accommodating portions 40 are provided. Such exchangeable electrode plates 41 are preferably arranged one by one in the cartridge housing portion 8 of the base unit 7. Each electrode array 9 is preferably supported by a lower substrate 11. It should be noted that the expressions “electrode array”, “electrode layout”, and “printed circuit board (PCB)” are used synonymously herein.

  The digital microfluidic system 1 includes at least one cover plate 12 having an upper substrate 13. Although it is particularly preferred to provide such a cover plate 12, at least some of the cover plates may be omitted, an alternative for holding the disposable cartridge 2 at a position inside the base unit of the microfluidic system 1 It may be replaced with a cover. Accordingly, at least one cover plate 12 may be disposed in one of the cartridge housing portions 8. A gap or cartridge housing portion 8 is defined by the upper substrate 13 of the cover plate 12 and the lower substrate 11 having the electrode array 9 or PCB, respectively. In the first modification (see the two cartridge housing portions 8 in the center of the base unit 7), the cartridge housing portions 8 are movable in a direction substantially parallel to the electrode array 9 of each cartridge housing portion 8, The disposable cartridge 2 to be inserted by sliding is accommodated. Such insertion from the front or top is performed by inserting the cartridge 2 into the final accommodation position in the cartridge accommodation portion 8 where the cartridge 2 is accurately placed after the disposable cartridge 2 is partially inserted. Assistance may be made to automatically pull in to transport. These cartridge housing portions 8 preferably do not include a movable cover plate 12. After performing the intended operation on the sample in the droplet, the used cartridge 2 may be automatically withdrawn and ejected, transported to an analytical terminal, or discarded.

  In the second modified example (see the two left and right cartridge housing portions 8 of the base unit 7), the cartridge housing portion 8 is configured to be movable with respect to each electrode array 9 of each cartridge housing portion 8. 12 is provided. The cover plate 12 is preferably configured to move about one or more hinges 16 and / or in a direction substantially perpendicular to the electrode array 9.

Similar to the possibility of inserting the disposable cartridge 2 into the cartridge accommodating portion 8, the possibility of inserting the exchangeable electrode plate 41 into the substrate accommodating portion 40 includes the following alternative configurations.
(A) The interchangeable electrode plate 41 is lowered vertically to the substrate housing portion 40 through each cartridge housing portion 8.
(B) The interchangeable electrode plate 41 is slid horizontally on the substrate housing portion 40 below each cartridge housing portion 8.
(C) The exchangeable electrode plate 41 is slid horizontally below each cartridge housing portion 8 and lifted substantially vertically to the substrate housing portion 40.

  In FIG. 1, only one exchangeable electrode plate 41 that can be slid and inserted by being inserted forward under the second cartridge housing portion 8 (counting from the left) is depicted. All the positions where the substrate accommodating portion 40 can be arranged are indicated by broken-line arrows.

  The digital microfluidic system 1 also controls the selection of the individual electrodes 10 of the at least one electrode array 9 described above, and the individual electrodes for manipulating droplets in the cartridge 2 by electrowetting. A central control unit 14 for supplying the following voltage pulses. As shown in part in FIG. 1, every single individual electrode 10 is operatively connected to a central control unit 14 and thus generates the potential required for methods known in the prior art. It can be addressed independently by this central control unit 14 with a suitable potential source.

  The at least one cover plate 12 preferably comprises a conductive member 15 that extends in a second plane and is substantially parallel to the electrode array 9 of the cartridge housing 8 to which at least one cover plate is assigned. In particular, the conductive member 15 of the cover plate 12 is preferably configured not to be connected to a ground potential source. If the applicant of the present invention has no connection between the conductive member 15 of the cover plate 12 and any certain (eg ground) potential, the conductive member 15 is also connected to the digital microfluidic system 1. It was found that it contributes to the movement of the manipulated droplets by electrowetting. Therefore, the cover plate 12 may be configured to be movable in any direction, and it is not necessary to consider electrical contact when selecting a particularly preferable movement of the cover plate 12. Accordingly, the cover plate 12 is also movable in a direction substantially parallel to the electrode array 9 in order to perform a linear, circular, or arbitrary movement with respect to each electrode array 9 of the base unit 7. It may be configured.

  FIG. 2 shows a cross-sectional view of one exemplary cartridge housing 8 having the disposable cartridge 2 of the first embodiment described herein. The cover plate 12 is mechanically connected to the base unit 7 of the digital microfluidic system 1 via a hinge 16, so that the cover plate 12 swings open and the disposable cartridge 2 is inserted into the cartridge through insertion from above. You may arrange | position to the accommodating part 8 (refer FIG. 1). The conductive member 15 of the cover plate 12 is made of a thin metal plate or metal foil attached to the upper substrate 13. Instead, the conductive member 15 of the cover plate 12 is configured as a metal layer stacked on the upper substrate 13. Such lamination of the conductive member 15 may be performed by a chemical or physical vapor deposition technique known per se.

  The cover plate 12 is configured to apply a force to the disposable cartridge 2 housed in the cartridge housing portion 8 of the base unit 7. This force urges the disposable cartridge 2 against the electrode array 9 to place the lower layer 3 of the cartridge as close as possible to the surface of the electrode array 9. Further, this force urges the disposable cartridge 2 to the optimum position of the electrode array 9 with respect to the punching mechanism 18 of the cover plate 12. The perforation mechanism 18 is configured to introduce a sample droplet into the gap 6 of the cartridge 2. The piercing mechanism 18 is constituted by a through hole 19, and the through hole 19 continues completely through the cover plate 12, and can be pierced by pushing the upper layer 4 of the cartridge 2 with the tip 20 of the piercing pipette. The tip 20 of the perforated pipette may be part of a portable pipette (not shown) or part of a pipette robot (not shown).

  In the case shown in FIG. 2, the electrode array 9 is covered with a dielectric layer 24. The electrode array 9 is fixed to the lower substrate 11 and all the individual electrodes 10 are electrically and operatively connected to the central control unit 14 (here only three connections of the ten electrodes 10 are shown). ) The electrode array 9 is disposed on a lower substrate 11 that is configured to be immovable. The digital microfluidics system 1 is configured to manipulate the sample in the droplet 23 in the disposable cartridge 2 including the gap 6. Accordingly, the sample in the droplet 23 is operated in the gap 6 of the disposable cartridge 2. The disposable cartridge 2 includes a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4, and the sample in the droplet 23 is manipulated in the gap 6. The lower layer 3 and the upper layer 4 include a hydrophobic surface 17 exposed in the gap 6 of the cartridge 2. The lower layer 3 and the upper layer 4 of the cartridge 2 are completely hydrophobic films, or at least have a hydrophobic surface exposed in the gap 6 of the cartridge 2. As is apparent from FIG. 2, the cartridge 2 does not have a conductive layer. The spacer 5 of the cartridge 2 is here configured as at least part of a main body including a compartment 21 for the reagents required for analysis applied to the sample droplet in the gap 6.

  FIG. 3 shows a cross-sectional view of one exemplary cartridge housing 8 having the disposable cartridge 2 of the second embodiment described herein. Unlike the above-described embodiment, the cover plate 12 is fixed and mechanically connected to the base unit 7 of the digital microfluidic system 1 so as not to move. The conductive member 15 of the cover plate 12 is composed of a thick metal plate attached to the upper substrate 13. Here, the cover plate 12 is not configured to apply force to the disposable cartridge 2 housed in the cartridge housing portion 8 of the base unit 7. Therefore, the cover plate 12 does not move from a predetermined position, and the disposable cartridge 2 may be disposed in the cartridge housing portion 8 through insertion from the front. Such a front insertion type usually involves movement of the disposable cartridge 2 in a direction parallel to the electrode array 9 (see FIG. 1). The base unit 7 is preferably provided with an insertion guide 25 in order to allow proper withdrawal of the disposable cartridge 2 and proper placement in the cartridge housing 8. These insertion guides 25 are preferably made of a self-lubricating plastic material and preferably leave a gap between them which is sufficient to slide the disposable cartridge 2 into place. Instead, the conductive member 15 of the cover plate 12 is composed of a metal plate, a metal foil, or a metal layer sandwiched between members of the upper substrate 13 (see FIG. 5A).

  The disposable cartridge 2 of FIG. 3 includes a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4, and the sample in the droplet 23 is manipulated in the gap 6. . The lower layer 3 and the upper layer 4 include a hydrophobic surface 17 exposed in the gap 6 of the cartridge 2. The lower layer 3 and the upper layer 4 of the cartridge 2 are completely hydrophobic films, or at least have a hydrophobic surface exposed in the gap 6 of the cartridge 2. Unlike what is shown in FIG. 2, the cartridge 2 has a dielectric layer 24 attached to or forming part of the lower layer 3. Therefore, the lower layer 3 is covered by the dielectric layer 24 or the lower layer 3 which itself comprises a dielectric layer. As a result, the electrode array 9 need not have such a dielectric layer 24. The spacer 5 of the cartridge 2 is here configured as at least part of a main body including a compartment 21 for the reagents required for analysis applied to the sample droplet in the gap 6. In this case, the electrode array 9 is covered with the dielectric layer 24.

  The electrode array 9 is fixed to the lower substrate 11, and the individual electrodes 10 are electrically and operatively connected to the central control unit 14 (here, three connections among the ten electrodes). Only shown). The electrode array 9 is disposed on the lower substrate 11 fixed so as not to move. The digital microfluidics system 1 is configured to manipulate a sample in a droplet in a disposable cartridge 2 that includes a gap 6. Accordingly, the sample in the droplet 23 is operated in the gap 6 of the disposable cartridge 2.

  The cover plate 12 also includes a perforation mechanism 18 configured to introduce sample droplets into the gap 6 of the cartridge 2. The piercing mechanism 18 includes a through hole 19, and the through hole 19 continues through the cover plate 12 completely, and can be pierced by pushing the upper layer 4 of the cartridge 2 with the tip 20 of the piercing pipette. The tip 20 of the perforated pipette may be part of a portable pipette (not shown) or part of a pipette robot (not shown). Here, the cover plate 12 is pushed through the through-hole 19 penetrating the cover plate 12 by the tip 20 of the perforated pipette, perforates the upper layer 4 of the cartridge 2, and draws out a part of the reagent from the compartment 21. An additional perforation mechanism 22 is provided to introduce a portion of the reagent into the gap 6. Here, the section 21 is configured as a notch portion of the main body of the spacer 5, and the notch portion is closed by the lower layer 3 and the upper layer 4.

  As in the first and second embodiments already described, the disposable cartridge 2 includes a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4. The sample in the droplet 23 is manipulated in the gap 6. The lower layer 3 and the upper layer 4 include a hydrophobic surface 17 exposed in the gap 6 of the cartridge 2. The first hydrophobic surface 17 'is arranged inside the lower layer 3 and the second hydrophobic surface 17 "is arranged inside the upper layer 4. The lower layer 3 and the upper layer 4 of the cartridge 2 are completely hydrophobic films. Or at least a hydrophobic surface exposed in the gap 6 of the cartridge 2. As is apparent from Fig. 2, the cartridge 2 does not have a conductive layer, where the spacer 5 of the cartridge 2 is It does not need to be configured as a body containing a compartment 21 for the reagents required for analysis applied to the sample droplet within the gap 6. Because these reagents are conventional pipette movements of portable pipettes or pipette robots. This is because it is added to the gap 6 by the above (see the upper part).

  As in the first and second embodiments already described, the disposable cartridge 2 includes a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4. The sample in the droplet 23 is manipulated in the gap 6. The lower layer 3 and the upper layer 4 include a hydrophobic surface 17 exposed in the gap 6 of the cartridge 2. The first hydrophobic surface 17 'is arranged inside the lower layer 3 and the second hydrophobic surface 17 "is arranged inside the upper layer 4. The lower layer 3 and the upper layer 4 of the cartridge 2 are completely hydrophobic films. Or at least a hydrophobic surface exposed in the gap 6 of the cartridge 2. As is apparent from Fig. 2, the cartridge 2 does not have a conductive layer, where the spacer 5 of the cartridge 2 is It does not need to be configured as a body containing a compartment 21 for the reagents required for analysis applied to the sample droplet within the gap 6. Because these reagents are conventional pipette movements of portable pipettes or pipette robots. This is because it is added to the gap 6 by the above (see the upper part).

  FIG. 4 shows an overview from above of the digital microfluidic system 1 comprising a central control unit 14 and a base unit 7 and 12 cartridge housings 8 each comprising a fixed cover plate 12. It is. The base unit 7 mounts the cartridge 2 of the sixth embodiment, and in the substantially vertical cartridge housing portion 8 having a substantially vertical electrode array 9 and a cover plate 12 (see FIG. 5). Particularly suitable for inserting cartridges. Such insertion is preferably performed by a robotized grip device at a liquid handling workstation (not shown).

  According to the present invention, the digital microfluidics system 1 also includes twelve substrate accommodating portions 40 for accommodating interchangeable electrode plates 41 each having an electrode array 9. In this exemplary embodiment of FIG. 4, all cartridge housing portions 8 and substrate housing portions 40 are grouped together and the substrate housing portion 40 is disposed immediately below the cartridge housing portion 8. These sets of the cartridge housing portion 8 and the substrate housing portion 40 are arranged in 3 rows and 4 columns here. In the upper cartridge housing portion 8 in the right column, the disposable cartridge 2 is empty, and the disposable cartridge 2 is shown on the right outside of the base unit 7. Further, the cartridge housing portion 8 and the substrate housing portion 40 in the center are shown as the disposable cartridge 2 and the exchangeable electrode plate 41 being empty as well, and on the right outer side of the base unit 7.

  FIG. 5 (see FIGS. 5A and 5B) shows one exemplary cartridge of the base unit 7 of the digital microfluidic system 1 having the disposable cartridge 2 of the sixth embodiment described herein. FIG. 6 is a cross-sectional view of the accommodating portion 8. As is readily apparent from FIG. 5A, the top insertable cartridge 2 is inserted into a substantially vertical cartridge housing 8 having a substantially vertical electrode array 9 and a cover plate 12. The disposable cartridge 2 includes a lower layer 3, an upper layer 4, and a spacer 5 that defines a gap 6 between the lower layer 3 and the upper layer 4, and the sample in the droplet is manipulated in the gap 6. The lower layer 3 and the upper layer 4 are provided with hydrophobic surfaces 17 ′ and 17 ″ exposed in the gap 6 of the cartridge 2. The lower layer 3 and the upper layer 4 of the cartridge 2 are completely hydrophobic films or the gap 6 of the cartridge 2. 2, the cartridge 2 has a dielectric layer attached to or forming part of the lower layer 3, such as that shown in FIG. As a result, the electrode array 9 need not have such a dielectric layer 24. The cartridge 2 is preferably filled with silicone oil.

  The electrode array 9 is fixed to the lower substrate 11 (which itself is immovably fixed inside the base unit 7), and all the individual electrodes 10 are electrically and operatively connected to the central control unit 14. (Only four of the 14 electrodes 10 are shown here). The digital microfluidics system 1 is configured to manipulate the sample in the droplet 23 in the disposable cartridge 2 including the gap 6. Accordingly, the sample of the droplet 23 is operated in the gap 6 of the disposable cartridge 2.

  The cover plate 12 is mechanically connected to the base unit 7 of the digital microfluidic system 1 or is completely integrated and not movable. Accordingly, the disposable cartridge 2 can be inserted into the cartridge housing 8 through the insertion from the front, which should be called the upper insertion type in practice in this situation of FIGS. 5A and 5B (compared to FIG. 4). Here, the conductive member 15 of the cover plate 12 is made of a metallic conductive member and is sandwiched between members of the upper substrate 13. Alternatively, the conductive member 15 of the cover plate 12 may be covered with a plastic layer instead of or in addition to a member (not shown) of the upper substrate 13.

  The spacer 5 also includes a piercing mechanism 18 configured to introduce sample droplets into the gap 6 of the cartridge 2. The drilling mechanism 18 is configured as an enlarged part of the spacer 5. This enlarged spacer portion preferably comprises a pierceable self-sealing membrane 31 that can be pushed through the tip 20 of the piercing pipette. The tip 20 of the perforated pipette may be part of a portable pipette (not shown) or part of a pipette robot (not shown). Automated transport of liquid into or out of the gap 6 of the cartridge 2 is simplified by the relatively large perforated area provided by this enlarged spacer portion of the cartridge 2. Assuming a gap width of about 1 to 3 mm, the width of this perforated region is preferably about 5 to 10 mm. Thus, it is approximately the size of a 96-well microplate and can easily be reached by an automated pipettor of a liquid handling system or liquid handling workstation. While providing space for the compartment 21 (see also FIG. 5B), the enlarged spacer portion of the cartridge 2 also includes a gripping surface for gripping by an automated robot gripper (not shown). This robot gripper preferably handles the outside of the cartridge of the digital microfluidics system 1 and is used for loading and unloading the cartridge 2 from the cartridge housing portion 8. Further, the enlarged spacer portion of the cartridge 2 includes a contact surface that contacts the surface of the base unit 7 when the cartridge 2 is correctly stored in the cartridge storage portion 8.

  Similarly to the case where the disposable cartridge 2 is taken in and out of each cartridge housing portion 8 and from each cartridge housing portion 8, the exchangeable electrode plate 41 can be inserted into and removed from each substrate housing portion 40. Good. It is further important to note that these receptacles 8, 40 are similar to or away from the spatial orientation shown and described above, and these receptacles 8, 40 are disposable cartridges 2 inserted into the cartridge receptacle 8. In the lower layer 3 so that it is in operative contact with the surface of each exchangeable electrode plate 41 (that is, the surface of the electrode array 9 or the surface of the dielectric layer 24 of the electrode array 9 of each exchangeable electrode plate 41). As long as the part 8 and the substrate housing part 40 are arranged close to each other, any spatial orientation can be applied.

  The electrode array 9 preferably extends to the foremost position relative to the surface of the base unit 7 so that the droplets 23 can move from the compartment 21 to individual positions on the printed circuit board (PCB) or electrode array 9. Also, moving the droplets 23 from the reaction position of the electrode array 9 to the compartment 21 in the opposite direction is very much, especially when the reaction products are analyzed outside the digital microfluidic system 1 and also outside the cartridge 2. preferable.

  FIG. 5B shows the upper insertion type cartridge 2 of FIG. 5A viewed from the cut surface B shown in FIG. 5A. The cross section passes through the gap 6 and passes between the lower layer 3 and the upper layer 4 of the self-contained disposable cartridge 2. In addition, the U-shaped portion cuts the spacer 5 disposed between the lower layer 3 and the upper layer 4, and the enlarged spacer portion is provided around the U-shaped portion, the lower layer 3 and the upper layer 4 in the cross section. It has been. Preferably, the U-shaped portion of the spacer 5 is made of a plastic material and is bonded or fused to the lower layer 3 and the upper layer 4. Preferably, the enlarged spacer portion is also provided by injection molding. Thereby, on the one hand, the compartment 21 can be formed below the pierceable membrane 31 and on the other hand a separating rod 32 can be provided which stabilizes the pierceable membrane 31. Preferably, such stability is provided by rear injection molding of the spacer portion enlarged relative to the separating bar 32 and the pierceable membrane 31. Preferably, the enlarged spacer portion is part of the U-shaped portion of the spacer 5 having the lower layer 3 and the upper layer 4.

  As already pointed out, the spacer 5 preferably also includes a drilling mechanism 18 that is composed of an enlarged portion of the spacer 5. Preferably, this enlarged spacer portion comprises a pierceable self-sealing membrane 31 that can be pushed through the tip 20 of the piercing pipette. The perforated pipette tip 20 may be part of a portable pipette (not shown) or part of a pipette robot (not shown). Here, the spacer 2 is provided with an additional perforation mechanism 22 for pushing the tip 20 of the perforated pipette through the self-sealing membrane 31 and for extracting, for example, silicon oil from the gap 6 of the cartridge 2. In the cartridge 2 of FIG. 5B, a droplet 23 (eg, a sample) is introduced by the piercing pipette tip 20 with the piercing mechanism 18 and then moved to the hydrophobic surface 17 ′ of the lower layer 3 toward the actual position. At the same time that the droplets 23 are introduced into the compartment 21 and into the gap 6, the same amount of silicon oil (or any other chemically inert liquid that is not mixed with the droplets 23) is added to the additional perforation mechanism 22. It is pulled out from each section 21. Instead of such a simultaneous adjustment of the liquid in the gap 6, the expected amount of oil or inert liquid may be removed immediately before and after the introduction of the droplets 23. In addition, the compartment 21 may serve as a container for accumulating more liquid than is necessary to generate a movable droplet 23 from this liquid. As a result, a plurality of such droplets 23 may be generated from a single liquid volume once introduced into at least one compartment 21. However, it is recommended to reserve one compartment 21 to draw oil or inert gas and another compartment 21 to draw the reagent product.

  In an alternative very simple embodiment (not shown), a disposable cartridge 2 comprising a lower layer 3 and an upper layer 4 with in each case a hydrophobic surface 17 ′, 17 ″ facing the gap 6 is replaced by a PCB. The mold may or may not be attached to the PCB for electrowetting, instead of using a cover plate 12 with a conductive member 15, a conductive film (e.g., aluminum foil) is used for the top layer 4. This conductive film allows electrowetting even when the conductive film is not grounded, instead of attaching an ungrounded conductive film to the cartridge. In addition, the outer layer 4 may be coated with a thin film on its outer surface. It may be laminated by chemical or physical vapor deposition techniques, and this thin conductive film on the outer surface of the upper layer 4 may consist of a conductive paint. Is to provide a conductive member 15 that extends in a second plane and is substantially parallel to the electrode array 9, said conductive member 15 being disposed on the upper layer 4 of the cartridge 2, While operating the sample in 23, it is not connected to a separate potential source.

  FIG. 6 shows a schematic view from above of the exchangeable electrode plate 41 that can be inserted into the substrate housing portion 40 of the digital microfluidic system 1. The lower substrate 11 of the exchangeable electrode plate 41 is composed of a printed circuit board (PCB). This top view shows a similar arrangement of an electrode array 9 such as a printed circuit board (PCB) of a droplet handling system disclosed in US patent application publication 13/188854. This was filed on July 22, 2011 by the present applicant and published in US Patent Application Publication 2013 / 0020202A1. This particular electrode array 9 of the system 40 is configured to accommodate the disposable cartridge 2 at the top thereof. The electrode array 9 is particularly suitable for cell material lysis, DNA fragment extraction and PCR amplification, genotyping mating experiments, and optical detection. However, unlike the PCB disclosed in US Patent Application Publication 2013 / 0020202A1, the lower substrate 11 of the electrode array 9 is fixed to the base unit 7 of the digital microfluidic system 1 so that it cannot be removed. Here, the lower substrate 11 and the electrode array 9 are a part of the exchangeable electrode plate 41 that can be taken in and out of the substrate housing portion 40 of the digital microfluidic system 1.

  When all experiments and measurements are complete, the cartridge 2 is safely discarded (along with the sample and waste in it) so that the researcher is not at risk from its contents. Then, the same exchangeable electrode plate 41 having the dedicated electrode array 9 may be used to decide to perform the same analysis using the same or another sample. In this case, the next disposable cartridge 2 is pushed onto the electrode array 9 and the next experiment can be performed. Alternatively, the execution of another experiment in which the exchangeable electrode plate 41 of the present invention having the dedicated electrode array 9 is not particularly useful may be determined. In this alternative case, another interchangeable electrode plate 41 with a different electrode array 9 suitable for the experiment or analysis to be performed may be selected. Thus, the exchangeable electrode plate 41 selected here is used while the sample for analysis or experiment of the sample in the droplet 23 attached to the hydrophobic surface 17 is operated in the gap 6 by electrowetting. It comprises an electrode array 9 configured to perform certain alternative analyzes or experiments within the gap 6 of the cartridge 2.

  In FIG. 6 (with reference to the top and bottom of the figure), many contact points, namely the electrical board contact elements 42, can be seen. An individual wire (not shown here for clarity of illustration) is connected to each individual electrode 10 having one of these electrical board contact elements 42. Further, the heater disposed on the lower substrate 11 of the exchangeable electrode plate 41 is also connected to a part of these electrical board contact elements 42. All the electrical board contact elements 42 are connected by physically contacting the appropriate number of electrical base unit contact elements 43 having the central control unit 14 of the digital microfluidic system 1. This central control unit 14 controls, for example, the necessary operation of the heater, the drilling mechanism 18 and the like and all the potentials of the necessary electrodes 10. Further, another contact point that contacts the ground potential source of the central control unit 14 is provided on both sides of the electrode array 9 and in the vicinity of the edge 44 of the PCB 11. Depending on the physical need and the method of inserting the replaceable electrode plate 41 into the substrate housing 40 of the digital microfluidic system 1, the electrical board contact element 42 is near one or more edges 44 of the PCB 11. May be arranged.

  The illustrated exchangeable electrode plate 41 is configured to be disposed in the substrate housing portion 40 of the digital microfluidic system 1 as shown in FIG. 1 or FIG. 4, for example. In each case, the electrical board contact element 42 of the exchangeable electrode plate 41 is engaged with the electrical base unit contact element 43 of the base unit 7 that is electrically connected to the central control unit 14 of the digital microfluidic system 1. It is comprised so that it may fit. Preferably, the lower substrate 11 supporting the electrode array 9 is formed of a printed circuit board (PCB), and the electrical board contact elements 42 are arranged in the vicinity of one or more edges 44 of the PCB. Particularly preferably, the individual electrodes 10 of the electrode array 9 are arranged and configured to manipulate droplets in the cartridge 2 by electrowetting and to perform specific analyzes or experiments.

  FIG. 7 shows a detailed cross-sectional view of FIG. However, here, the electrode array 9 is disposed on the exchangeable electrode plate 41 of the first embodiment in electrical contact. Here, the electrical board contact element 42 is substantially formed on at least one edge 44 of the lower substrate 11 in a direction perpendicular to the first plane in which at least one electrode array 9 of the replaceable electrode plate 41 extends substantially. It is configured as a rigid plate or knoll extending into Preferably, in order to mount such a replaceable electrode plate 41, a plurality of electrical equipment base unit contact elements 43 electrically connected to the central control unit 14 of the digital microfluidic system 1 are connected to the individual electrodes 10 In order to safely engage and engage with the plurality of electrical board contact elements 42 of the exchangeable electrode plate 41 that is electrically connected to each other, it extends substantially vertically and is elastic in the horizontal direction. It consists of a leaf spring.

  FIG. 8 shows a detailed cross-sectional view of FIG. However, here, the electrode array 9 is disposed on the exchangeable electrode plate 41 of the second embodiment in electrical contact. Here, the electrical board contact element 42 substantially extends in a direction parallel to a first plane in which at least one electrode array 9 extends substantially below and in the vicinity of the edge 44 of the lower substrate 11. It is configured as a rigid plate or knoll. Preferably, in order to mount such a replaceable electrode plate 41, a plurality of electrical equipment base unit contact elements 43 electrically connected to the central control unit 14 of the digital microfluidic system 1 are connected to the individual electrodes 10 In order to safely engage and fit with the plurality of electrical circuit board contact elements 42 of the exchangeable electrode plate 41 electrically connected to each other, it substantially extends in the straight direction and is elastic in the vertical direction. It is comprised by the pin supported elastically or elastically. As shown, a common (here vertically arranged) or individual (here horizontally arranged) insertion guide is inserted into and out of each receptacle 8, 40 and the disposable cartridge 2 and As well as easy removal of the exchangeable electrode plate 41, safe and accurate insertion is facilitated.

  FIG. 9 shows a typical multi-level “instrument platform”, ie a standard base with all the common modules that are always needed when manipulating droplets by electrowetting. 1 is a schematic diagram of a digital microfluidic system 1 including a unit 7. FIG. Such a module is, for example, a digital analog (D / A) board 45, a high voltage relay module 46, and a vacuum (with an O-ring 53) for fixing the cartridge clamp module 47 or the cartridge 2 to the replaceable PCB 41. It comprises a mechanism 49, embedded software 51, which is preferably loaded into the central control unit 14 of the base unit 7, and a graphic user interface (GUI) 52, which preferably consists of a touch screen.

  Additional modules, such as an optical module 48 for analysis of the sample contained in the droplet 23 (eg one-sided optical detection of fluorescence emission or optical transmission detection of absorbance), or a magnetic actuator module for attracting magnetic beads 50 may be integrated into all digital microfluidic systems 1 or only when necessary. Such an “instrument platform” for performing a series of specific experiments or analyzes is configured as a stand-alone instrument further comprising a set of replaceable PCBs and replaceable cartridges suitable for each experiment or analysis. Yes.

  Different arrangements of the electrical board contact element 42 and the electrical base unit contact element 43 are within the choice of one of ordinary skill in the art reading this application.

  The method of manipulating the sample in the droplet 23 adhering to the hydrophobic surface 17 may include providing a first hydrophobic surface 17 ′ of the lower layer 3 of the disposable cartridge 2. This lower layer 3 is arranged substantially parallel above the electrode array 9 of the digital microfluidic system 1. The electrode array 9 includes a plurality of individual electrodes 10 that extend in the first plane and are supported by the lower substrate 11 of the base unit 7 of the digital microfluidic system 1. The electrode array 9 controls the selection of the individual electrodes 10 of the electrode array 9 and allows the individual electrodes 10 to be individually controlled in order to manipulate the droplets 23 on the first hydrophobic surface 17 'by electrowetting. It is connected to the central control unit 14 of the digital microfluidic system 1 for supplying voltage pulses. The method may further include providing a second hydrophobic surface 17 ″ at a position substantially parallel to the first hydrophobic surface 17 ′ and at a certain distance. A gap 6 is formed between the hydrophobic surface 17 ′ and the second hydrophobic surface 17 ″. Preferably, such a gap 6 is defined by a spacer 5, which comprises a lower layer 3 comprising a first hydrophobic surface 17 ′ and an upper layer 4 comprising a second hydrophobic surface 17 ″. It may further include providing a cover plate 12 having an upper substrate 13. The cover plate 12 includes a conductive member 15 that is substantially parallel to the electrode array 9 and extends in a second plane. Particularly preferably, the conductive member 15 of the cover plate 12 is not connected to a separate potential source while manipulating the sample in the droplet 23.

  In all illustrated or described embodiments, the gap 6 of the disposable cartridge 2 is preferably substantially filled with silicone oil. Also preferably, the lower layer 3 and the upper layer 4 of the cover plate 12 are completely hydrophobic or comprise hydrophobic surfaces 17 ′, 17 ″ exposed in the gap 6 of the cartridge 2. The gap 6 of the disposable cartridge 2 After the electrowetting and manipulation of at least one droplet 23 having the same, the result of the manipulation or analysis can be evaluated while the disposable cartridge 2 is still in the cartridge housing 8. That is, the digital microfluidic system 1 or the digital micro Utilizing a workstation analysis system with an integrated fluidic system 1. Alternatively, the disposable cartridge 2 can be removed from the base unit 7 of the digital microfluidic system 1 and analyzed elsewhere. Good.

  After analysis, the disposable cartridge 2 can be disposed and the electrode array 9 can be reused. When working with the cartridge 2 of the first or second embodiment, the components of the digital microfluidic system 1 do not come into contact with the sample or reagent, so that such reuse of other disposable cartridges 2 is an intermediate wash. Can be done immediately without. When working with the cartridge 2 of the third or fourth embodiment, the through-hole 19 of the cover plate 12 of the digital microfluidic system 1 may come into contact with the sample or the reagent. Such reuse can be performed after intermediate cleaning or after replacement of the cover plate 12.

  An object of the present invention is to provide a removable and disposable film that separates droplets 23 from electrode array 9 and from upper plate 12 while manipulating droplets 23 by electrowetting. Removable and disposable films are provided as the lower layer 3 and the upper layer 4 of the cartridge 2 as illustrated in six different embodiments of self-contained disposable cartridges 2 shown in the above specification. It is preferable.

  In a preferred embodiment, the lower layer 3 of the cartridge 2 is sucked into the PCB by a vacuum. A small vent on the PCB is connected to a vacuum pump for this purpose. By performing such vacuum suction to the lower layer 3, the use of other liquids or adhesives for good contact of the lower layer 3 of the cartridge 2 with the surface of the electrode array 9 can be avoided.

  Any combination of features of the embodiment of the cartridge 2 that are different from those disclosed herein, which are reasonable to those skilled in the art, are included in the spirit and scope of the present invention.

  The reference numerals shown in the figures refer to the same elements of the exchangeable electrode plate 42 and the digital microfluidic system 1 of the present invention, even though not specifically mentioned in each case.

DESCRIPTION OF SYMBOLS 1 Digital microfluidics system 2 Disposable cartridge 3 Lower layer 4 Upper layer 5 Spacer 6 Gap 7 Base unit 8 Cartridge accommodating part 9 Electrode array 10 Individual electrode 11 Lower substrate, PCB
12 Cover plate 13 Upper substrate 14 Central control unit 15 Conductive member 16 Hinge 17 Hydrophobic surface 17 'First hydrophobic surface 17 "Second hydrophobic surface 18 Drilling mechanism 19 Through hole 20 Perforated pipette tip 21 Compartment 22 Additional Punching mechanism 23 Droplet 24 Dielectric layer 25 Insertion guide 26 Disposable pipette tip 27 Punching pin 31 Punchable membrane 32 Separating rod 40 Substrate housing part 41 Exchangeable electrode plate 42 Electrical board contact element 43 Electrical base unit contact element 44 PCB Edge 45 Digital analog (D / A) input / output (I / O) board 46 High voltage relay module 47 Cartridge clamp module 48 Optical module 49 Vacuum mechanism 50 Magnetic actuator module 51 Embedded software 52 Graphic user interface (GU) )
53 O-ring

Claims (18)

Digital to manipulate samples in droplets in a disposable cartridge (2) comprising a lower layer (3), an upper layer (4), and a gap (6) between the lower layer (3) and the upper layer (4) A microfluidics system (1),
The digital microfluidics system (1)
(A) a base unit (7) having at least one cartridge housing portion (8) provided for placing the disposable cartridge (2);
(B) at least one electrode array (9) extending substantially in the first plane, comprising a plurality of individual electrodes (10) and supported by the lower substrate (11);
(C) controlling the selection of the individual electrodes (10) of the at least one electrode array (9) and manipulating these individual electrodes (10) with droplets in the cartridge (2) by electrowetting A central control unit (14) for supplying individual voltage pulses for
The digital microfluidic system (1) further includes at least one substrate housing portion (40) disposed in one of the cartridge housing portions (8) of the base unit (7), and each of the substrate housing portions. (40) the is configured to place the replacement electrode plate (41) apart independently of the disposable cartridge (2), before Symbol cartridge housing part (8) and the substrate receiving portion (40) because it is very close each other, the surface or the dielectric top of the electrode array 9 of each switching electrode plate 41 of the disposable cartridge to be inserted (2) the electrode array in the lower layer (3) is (9) in contact with the surface of the body layer 24, each of said switching electrode plate (41) is the collector which is electrically connected to the individual electrodes (10) of said electrode array (9) and said electrode array (9) Each of the substrate housing portions (40) includes a plurality of electrical base unit contact elements (43) electrically connected to the central control unit (14). The contact element (43) is configured to be engaged with the electrical board contact element (42) of the exchangeable electrode plate (41) disposed in the board housing part (40). Digital microfluidics system (1). The at least one substrate housing portion (40) is disposed below, above, or laterally of the cartridge housing portion (8) of the base unit (7), and the arrangement direction of the cartridge housing portion (8). The exchangeable electrode plate (41) to be inserted into the base unit (7) of the digital microfluidic system (1) according to the above is placed. The digital microfluidic system (1) according to 1.   The plurality of electrical base unit contact elements (43) electrically connected to the central control unit (14) of the digital microfluidic system (1) extend in a substantially vertical direction, and the individual electrodes ( 10) It is constituted by a horizontally elastic leaf spring that is safely and individually engaged with the plurality of electrical board contact elements (42) of the exchangeable electrode plate (41) electrically connected to 10). Digital microfluidic system (1) according to claim 2, characterized in that.   The plurality of electrical base unit contact elements (43) electrically connected to the central control unit (14) of the digital microfluidic system (1) are electrically connected to the individual electrodes (10). The interchangeable electrode plate (41) extends substantially vertically and is elastic in the horizontal direction for safe and individual engagement with the plurality of electrical board contact elements (42). Digital microfluidic system (1) according to claim 2, characterized in that it consists of pins that are elastically or elastically supported. The at least one substrate receiving portion (40) is substantially
(A) The exchangeable electrode plate (41) is lowered in the vertical direction into the substrate housing part (40) through each cartridge housing part (8), or (b) below each cartridge housing part (8). The exchangeable electrode plate (41) is slid in the horizontal direction in the substrate housing portion (40), or (c) the interchangeable electrode plate (41) below each cartridge housing portion (8). The exchange mold is inserted into the base unit (7) of the digital microfluidic system (1) by sliding it horizontally and lifting it into the substrate housing (40) substantially vertically. 3. The digital microfluidic system (1) according to claim 2, characterized in that the electrode plate (41) is mounted independently of the disposable cartridge (2). .   To manipulate a sample in a droplet, wherein the lower layer (3) and the upper layer (4) comprise a hydrophobic surface (17) exposed in the gap (6) of the disposable cartridge (2) The digital microfluidic system (1) according to claim 1, further comprising a disposable cartridge (2).   The disposable cartridge (2) has a spacer (5) configured as at least a part of a main body including a compartment (21) for reagents necessary for analysis or experiment to be added to a sample droplet in the gap (6). The microfluidic system (1) according to claim 6, further comprising:   7. The lower layer (3) of the cartridge (2) is covered by a dielectric layer (24) or the lower layer (3) itself is made of a dielectric material. Digital microfluidics system (1).   The digital microfluidic system 1 further includes at least one cover plate (12) having an upper substrate (13), and the at least one cover plate (12) is disposed in the cartridge housing portion (8). The at least one cover plate (12) is in a second plane with respect to the electrode array (9) of the cartridge housing portion (8) to which the at least one cover plate (12) is assigned. The digital microfluidic system according to claim 1, further comprising a conductive member (15) extending substantially in parallel, wherein the conductive member (15) is not connected to a potential source. (1).   The plurality of electrical board contact elements (42) including the electrode array (9) supported by the lower substrate (11) and electrically connected to the individual electrodes (10) of the electrode array (9). At least one replaceable electrode plate (41), and the replaceable electrode plate (41) is placed in the disposable cartridge (2) in the substrate housing portion (40) of the digital microfluidic system (1). The electrical circuit board contact element (42) is electrically connected to the central control unit (14) of the digital microfluidic system (1). 2. The device according to claim 1, wherein the base unit is configured to engage with the electrical base unit contact element of the base unit. Tal microfluidics system (1).   A plurality of electrical boards comprising an electrode array (9) and a lower substrate (11) that supports the electrode array (9) and electrically connected to the individual electrodes (10) of the electrode array (9) It is an exchangeable electrode plate (41) provided with a contact element (42), Comprising: The said exchangeable electrode plate (41) is the said board | substrate accommodating part (40) of the digital microfluidics system (1) of Claim 1 And the electric circuit board contact element (42) of the exchangeable electrode plate (41) is arranged separately from the disposable cartridge (2). It is configured to engage with the electrical base unit contact element (43) of the base unit (7), which is electrically connected to the central control unit (14) of the index system (1). It features a replacement electrode plate (41).   The lower substrate (11) that supports the electrode array (9) is formed of a printed circuit board (PCB), and the electrical board contact element (42) is located near one or more edges (44) of the PCB. Arranged together, the individual electrodes (10) of the electrode array (9) to manipulate droplets in the disposable cartridge (2) by electrowetting and to perform specific analyzes or experiments The exchangeable electrode plate (41) according to claim 11, characterized in that it is arranged and configured.   The electrical board contact element (42) is formed on the lower substrate in a direction perpendicular to a first plane in which the at least one electrode array (9) of the exchangeable electrode plate (41) extends substantially. 12. Exchangeable electrode plate (41) according to claim 11, characterized in that it is configured as a rigid plate or ridge substantially extending on at least one edge (44).   The electrical board contact element (42) is formed on the edge (44) of the lower board (11) in a direction parallel to a first plane in which the at least one electrode array (9) extends substantially. 12. Exchangeable electrode plate (41) according to claim 11, characterized in that it is configured as a rigid plate or ridge substantially extending below and in the vicinity.   An electronic chip and dedicated software for performing a specific experiment or analysis are provided, and the electronic chip and the dedicated software of the interchangeable electrode plate (41) are connected to the base unit (7) of the digital microfluidic system (1). ), The software included in the base unit (7) of the digital microfluidics (1) is automatically updated when the interchangeable electrode plate (41) is inserted into the digital microfluidics (1). The exchangeable electrode plate (41) according to claim 11, wherein:   The exchangeable electrode plate (41) according to claim 11, characterized in that at least one of the electrode arrays (9) is covered by a dielectric layer (24). A method of manipulating a sample in a droplet (23) adhering to a hydrophobic surface (17),
(A) preparing a digital microfluidic system (1) according to claim 1,
(B) Separately prepare the cartridge (2) according to claim 6,
(C) separately comprising the step of preparing the exchangeable electrode plate (41) according to claim 10,
During the analysis or experiment, the exchangeable electrode plate (41) is operated in the gap (6) by the sample in the droplet (23) adhering to the hydrophobic surface (17) by electrowetting. A method comprising an electrode array (9) configured to perform a specific analysis or experiment within said gap (6) of (2). A method of manipulating a sample in a droplet (23) adhering to a hydrophobic surface (17),
(A) preparing a digital microfluidic system (1) according to claim 1,
(B) Separately prepare the cartridge (2) according to claim 6,
(C) separately comprising the step of preparing the exchangeable electrode plate (41) according to claim 11,
During the analysis or experiment, the exchangeable electrode plate (41) is operated in the gap (6) by the sample in the droplet (23) adhering to the hydrophobic surface (17) by electrowetting. A method comprising an electrode array (9) configured to perform a specific analysis or experiment within said gap (6) of (2).

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