197 results about "Digital microfluidics" patented technology

Described herein are digital microfluidic (DMF) devices and corresponding methods for managing reagent solution evaporation during a reaction. Reactions on the DMF devices described here are performed in an air or gas matrix. The DMF devices include a means for performing reactions at different temperatures. To address the issue of evaporation of the reaction droplet especially when the reaction is performed at higher temperatures, a means for introducing a replenishing droplet has been incorporated into the DMF device. A replenishing droplet is introduced every time when it has been determined that the reaction droplet has fallen below a threshold volume. Detection and monitoring of the reaction droplet may be through visual, optical, fluorescence, colorimetric, and / or electrical means.

Air-matrix digital microfluidics (DMF) apparatuses and methods of using them to prevent or limit evaporation and surface fouling of the DMF apparatus. In particular, described herein are air-matrix DMF apparatuses and methods of using them in which a separate well that is accessible from the air gap of the DMF apparatus isolates a reaction droplet by including a cover to prevent evaporation. The cover may be a lid or cap, or it may be an oil or wax material within the well. The opening into the well and / or the well itself may include actuation electrodes to allow the droplet to be placed into, and in some cases removed from, the well. Also described herein are air-matrix DMF apparatuses and methods of using them including thermally controllable regions with a wax material that may be used to selectively encapsulate a reaction droplet in the air gap of the apparatus.

The invention discloses a closed-loop control digital microfluidic system and a method thereof, and relates to the technical field of microfluidics, and the method comprises the following steps: initializing a digital microfluidic chip electrode array, setting an electrode spacing, an electrode size and a voltage upper limit, collecting a no-load state signal, and generating initial reference data; liquid drops are formed at the preset position of the digital micro-fluidic chip, and according to the initial reference data, the initial position, the volume and the form information of the liquid drops are collected, and a liquid drop initial state data set is generated; inputting the initial state data set of the liquid drop into a pre-trained closed-loop prediction model, performing kinetic analysis and trajectory prediction calculation, generating an expected motion trajectory of the liquid drop, and comparing the expected motion trajectory with the real-time state data flow of the liquid drop to generate deviation feedback data of the liquid drop; and dynamically adjusting the initial driving voltage parameter according to the droplet deviation feedback data to generate a closed-loop driving voltage sequence. The liquid drop trajectory control precision is improved, and motion errors caused by environmental disturbance and electrode response differences are reduced.

The invention discloses a liquid drop routing method under fluid constraint in a digital micro-fluidic biochip based on reinforcement learning and imitation learning, and aims to solve the technical problems of low planning efficiency, low success rate and weak generalization ability of a traditional liquid drop routing algorithm under fluid constraint. The method adopts a strategy combining imitation learning and reinforcement learning and comprises the following steps: firstly, generating expert data by utilizing an expert algorithm meeting fluid constraint after transformation, and pre-training a network model through imitation learning to enable the network model to quickly grasp a basic routing strategy; the model and environment interaction are autonomously optimized through reinforcement learning, and the adaptability to the dynamic environment is improved. And finally fusing the weights to form a final model. Through the hybrid training framework, the success rate and planning efficiency of droplet routing are remarkably improved, and the generalization ability of the model to chip environments with different sizes is enhanced.

Compared with the prior art, the utility model discloses a digital micro-fluidic driving system, which has the following beneficial effects: through mutual cooperation of a main control unit, a high-voltage output unit, a detection unit, an adapter, an array, a distributor and a concentrator, synchronous and asynchronous driving of various types of digital micro-fluidic chips can be realized; the complexity of liquid drop motion planning of the system is increased; chip adaptation is completed by synchronously updating a chip driving electrode array, a connection relation between chip driving electrodes and signal output channels and a channel address grouping result, complex droplet operations of different chips are cooperatively operated through one system, the cost is saved, and the process is simplified; the liquid drops on the chip are subjected to double constraint through the adjacency relation of the electrodes and the addresses of the signal channels, the global optimal liquid drop movement path can be obtained, the liquid drop movement efficiency is guaranteed, and the fault-tolerant capability of controlling the liquid drops can be enhanced under the scene of high flux and multi-liquid drop path coupling.

The invention relates to the field of cell analysis, and provides a multi-mode digital micro-fluidic system and method for cell sorting analysis, the system comprises an active digital micro-fluidic platform, the active digital micro-fluidic platform comprises a micro-fluidic chip, an upper computer control system and an FPGA hardware circuit, an upper computer generates a liquid drop path planning instruction, the FPGA hardware circuit converts the liquid drop path planning instruction into an electrode driving signal, and the electrode driving signal is transmitted to the micro-fluidic chip; the nanoliter-grade liquid drops are driven to change between the electrodes; the optical tweezers platform comprises a laser device, an optical microscope and a CMOS camera, laser beams are generated by the laser device to form a three-dimensional optical potential well, the laser beams are transmitted into the micro-fluidic chip through the optical microscope to realize non-contact control on cells, and the CMOS camera records images and transmits the images back to the upper computer; the objective table clamp is used for realizing cooperative control of the optical tweezers and the active digital microfluidics; and the image recognition system is used for recognizing morphological characteristics of cells in the liquid drops based on a convolutional neural network and screening target cells. According to the invention, integration of high-throughput nondestructive cell sorting and in-situ multi-modal analysis is realized.

The invention discloses a digital micro-fluidic chip temperature control system, and the system comprises a heat conduction silica gel pad which is used for bearing a digital micro-fluidic chip; the array temperature sensor is used for sensing the temperature of the digital micro-fluidic chip on the heat-conducting silica gel pad; the heater is arranged below the heat conduction layer; the heat dissipation plate is arranged below the heater; the central processing unit is electrically connected with the heater, the temperature sensor and the heat dissipation plate, and the central processing unit enables the digital micro-fluidic chip to be at the optimal temperature in the amplification reaction circulation sub-process by adjusting the heating power of the heater and the rotating speed of the heat dissipation plate; the heater comprises a plurality of independent temperature control sub-areas which are used for being synchronously started in sequence after cycle times are spaced. By combining temperature control with an artificial intelligence method, real-time monitoring and prediction of the temperature of the reaction chamber are realized, and through real-time monitoring and prediction of the temperature of the reaction chamber and setting of the independent temperature control sub-regions, a plurality of amplification reaction cycles are started at intervals, so that the flexibility of amplification reaction setting is improved.

A digital microfluidic (DMF) system, DMF cartridge, and method including integrated refractive index (RI) sensing is disclosed. The digital microfluidic DMF system and DMF cartridge may include, for example, a RI sensor (or sensor surface) directly in the droplet operations gap of a DMF cartridge. The digital microfluidic DMF system may include, for example, the DMF cartridge, one or more illumination sources, one or more optical measurement devices, and a controller. Additionally, a method of using the DMF system and DMF cartridge that includes integrated RI sensing is provided.

The invention discloses a full-automatic high-concentration sample enrichment device and method based on a digital micro-fluidic chip, the device comprises a liquid mixing system, a filling unit and a micro-fluidic chip, the liquid mixing system comprises an injection unit, a liquid storage unit and a liquid mixing cavity, the liquid storage unit, the liquid mixing cavity and the micro-fluidic chip are sequentially connected in series through conduits; the injection unit is used for injecting the sample solution and the magnetic bead solution in the liquid storage unit into the liquid mixing cavity for mixed incubation; the injection unit is used for injecting the incubated magnetic bead sample mixed solution into the micro-fluidic chip; wherein the micro-fluidic chip is used for driving injected mixed liquid to an enrichment area of the micro-fluidic chip, and magnetic beads in the mixed liquid passing through the enrichment area successively are adsorbed and positioned by controlling a magnetic element to move to the enrichment area. The detection precision of the micro-fluidic chip is improved, and the occasion requirements of high-sensitivity detection and analysis are met.

The invention provides a digital micro-fluidic chip and application, and relates to the technical field of chips. The method comprises the steps that if a driving instruction including address information of an electrode is received through a signal line in a signal line cluster corresponding to a functional area, the electrode indicated by the address information is gated in the functional area according to the address information, and the address information includes a row number and a column number of an operation position in the functional area; in the area positions in the functional area array, one operation position corresponds to at least one electrode; and executing corresponding operation at the operation position of the electrode through the electrode. According to the invention, multi-dimensional addresses can be set for the operation positions in the functional area, so that the same functional area can be reused, the number of the operation positions in the functional area is increased, and the chip has the capability of controlling a huge amount of micro-droplets.

The invention discloses an immunodetection system and method based on a digital micro-fluidic chip, the system comprises a micro-fluidic chip, a heating unit, a magnetic field loading unit, a fluorescence detection unit and a control unit, the micro-fluidic chip comprises a liquid injection area, a magnetic mixing area, a magnetic separation area, a detection area, a waste liquid area and an electrode array; the electrode array covers each area and drives liquid drops in the areas to move; the control unit is used for controlling the electrode array to drive the movement sequence and position of the liquid drops in each region according to an immunodetection process; wherein the heating unit is used for regulating and controlling the immune reaction temperature of liquid drops in the magnetic mixing area, and driving the liquid drops to continuously move in the magnetic mixing area through the electrode array covered by the magnetic mixing area, so that samples, magnetic beads and fluorescent microspheres in the liquid drops are fully mixed and react. The immunoreaction time is greatly shortened, the magnetic mixing uniformity is greatly improved, and the immunodetection efficiency and accuracy are improved.

The invention discloses a device and a method for preparing a biochemical liquid drop sample regulated and controlled by a sound field and an electric field. The device comprises a sound focusing spray head, a three-axis motion platform and a digital micro-fluidic chip, acoustic waves generated by the Archimedes spiral interdigital transducer are adopted, the acoustic waves are focused at the nozzle when being transmitted to the tail end of the spray head, breakage and generation of liquid drops are promoted, and the size of the printing liquid drops is effectively controlled by adjusting sine alternating voltage parameter values and adjusting the printing speed of the liquid drops at the nozzle. The micro-electrodes integrated with the dielectrophoresis technology are adopted to generate dielectrophoretic force, directional movement of micro-droplets under the action of an electric field is achieved, by adjusting sine alternating voltage parameter values, the size of the moving droplets is adjustable, the droplets move to the mixing area, the mixing area vibrates under the resonant frequency of the piezoelectric plate, the droplets are promoted to be fully mixed, and the micro-droplets are fully mixed. The preparation of a biochemical liquid drop sample is realized; according to the invention, preparation of various biochemical liquid drop samples and fusion and mixing of various liquid drops can be realized, and a foundation is laid for further detection.

A digital microfluidic chip and a use thereof. The digital microfluidic chip comprises: a first substrate (10), comprising a first base (11), the first base (11) being provided with a sample input hole (12); an interposer layer (20), one side of the interposer layer (20) being connected to the first substrate (10), the interposer layer (20) comprising a flow channel in communication with the sample input hole (12), the flow channel sequentially comprising a droplet generation region (21), a droplet deceleration region (22) and a digital microfluidic region (23), the droplet generation region (21) being configured to generate micro-droplets, and the droplet deceleration region (22) being configured to decelerate the micro-droplets; a second substrate (30), the second substrate (30) being connected to a side of the interposer layer (20) distant from the first substrate (10), the second substrate (30) comprising a driving electrode (31), and the driving electrode (31) being configured to drive the micro-droplets in the interposer layer (20) to move.

The utility model relates to a temperature control component for a digital micro-fluidic chip and a reagent temperature control device, the temperature control component comprises a flow channel substrate, a first temperature control assembly and a negative pressure module, the flow channel substrate is provided with at least one temperature control flow channel, the temperature control flow channel is configured to contain liquid drops, and at least partial area of the temperature control flow channel is provided with a breathable waterproof layer; the first temperature control assembly is arranged on one side of the flow channel substrate and is configured to heat or cool the temperature control flow channel; the negative pressure module is connected to the flow channel substrate and / or the first temperature control assembly and pumps out bubbles in the liquid drops or gas dissolved in the liquid drops through the breathable waterproof layer. Compared with the prior art, the reagent heating device has the advantages that the reagent can be independently heated, direct heating on the surface of the chip is avoided, the chip material is not limited, the heating efficiency is high, the heating time is short, and the problem of bubbles caused by high-temperature heating of the reagent can be solved; and when the heating temperature is high, the problems that the reagent adheres to the chip and the performance of the chip is reduced cannot occur.

The present application relates to a kind of micro nuclear magnetic resonance probe and nucleic acid, antibody nuclear magnetic resonance detection method.Micro nuclear magnetic resonance probe includes the parallel arrangement of first plane shimming coil, nuclear magnetic resonance micro coil chip, digital microfluidic chip and second plane shimming coil in sequence, digital microfluidic chip is single pole plate form, the microstrip of medium substrate on nuclear magnetic resonance micro coil chip is annular microstrip coil, nuclear magnetic resonance micro coil chip and digital microfluidic chip are spaced apart.There is beneficial effect: through digital microfluidic chip control droplet, with simple structure, easy integration advantage;Annular microstrip coil can generate a uniform B1 field that matches the shape of droplet, can improve the filling factor of trace sample droplet;Nucleic acid, antibody modified magnetic particle probe can enhance nuclear magnetic resonance detection sensitivity, by quantitative analysis the change amount of relaxation time and the concentration of target detection substance, nucleic acid, antibody quantitative detection can be realized.

The invention discloses a nucleic acid extraction and enrichment system. The system comprises a mixing and splitting module, a cleaning and eluting module, a liquid drop control module, a pressure control module and an extrusion module. The nucleic acid extraction and enrichment system can complete 10-20 times of nucleic acid enrichment, solves the problem of false negative in nucleic acid detection caused by lower virus concentration at the initial stage of infection, can reduce the influence of personnel operation on the result, reduces aerosol pollution, and also can reduce the reagent dosage.

The application relates to the technical field of microfluidic chips and optical tweezers, in particular to a novel combination of an optical tweezers and a digital microfluidic chip structure manufacturing method, which comprises an upper chip substrate and a lower chip substrate; the upper chip substrate and the lower chip substrate are matched to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete planar processing; the upper chip substrate comprises a hydrophobic layer, an insulating layer, an electrode layer and a glass layer; liquid crystal is arranged between the upper chip substrate and the lower chip substrate, and the liquid crystal contains cells. The application combines the optical tweezers and the digital microfluidic chip structure and the manufacturing method thereof, so that the photoelectric current control chip can be reused, the cost is reduced, the liquid phase separation capacity of small substances in microdroplets is improved, the problems of cell liquid phase separation, fixed time culture and detection can be solved, and the two technologies are not conflicted on the chip.

The invention relates to the technical field of microfluidics and molecular diagnosis, and discloses a digital micro-fluidic chip for preparing an NGS methylation library. Comprising a bearing substrate, an electrode array used for electrowetting driving is formed on the upper surface of the bearing substrate to serve as a liquid drop conveying channel, the bearing substrate is divided into a plurality of functional areas which are sequentially arranged from the first side to the second side, the areas are communicated with one another through the liquid drop conveying channel, and micro-liquid drops are transferred and distributed among the areas. The upper cover is arranged opposite to the bearing substrate, a micro-droplet containing cavity is defined between the upper cover and the bearing substrate through a spacing frame arranged around the electrode array, and the upper cover is provided with a plurality of liquid inlet and outlet holes corresponding to the functional areas respectively. The chip is driven by the electrode array, so that micro-droplets entering the reagent sample introduction area and the sample introduction area through the liquid inlet and outlet holes are sequentially conveyed to the reaction area, and the micro-droplets after reaction are transferred to the taking-out area and are output through the liquid inlet and outlet holes, so that at least part of steps in the NGS methylation library preparation process are completed.

The application discloses a kind of closed loop control digital microfluidic system and method thereof, it is related to microfluidic technical field, including, initialization digital microfluidic chip electrode array, set electrode spacing, electrode size and voltage upper limit, and collect empty load state signal, generate initial reference data;Droplet is formed in the predetermined position of digital microfluidic chip, and according to initial reference data, collect droplet initial position, volume and morphological information, generate droplet initial state data set;Droplet initial state data set is input after pre-training closed loop prediction model, carries out dynamics analysis and trajectory prediction calculation, generates droplet expected motion trajectory, and compares with droplet real-time state data flow, generates droplet deviation feedback data;According to droplet deviation feedback data, dynamically adjust preliminary driving voltage parameter, generate closed loop driving voltage sequence.The application improves droplet trajectory control precision, reduces environmental disturbance and the motion error brought by electrode response difference.

The invention discloses an RPA-CRISPR nucleic acid detection system and method based on a digital micro-fluidic chip, the system comprises a micro-fluidic chip, a heating unit, a fluorescence detection unit and a control unit, the micro-fluidic chip comprises a first liquid injection zone, a first reaction zone, a quantitative liquid separation zone, a second reaction zone, a second liquid injection zone, a detection zone and an electrode array; the electrode array covers each area and drives liquid drops in the areas to move; the control unit is used for controlling the electrode array to drive the movement sequence and position of the liquid drops in each region according to a nucleic acid detection process; wherein the electrode array covered by the quantitative liquid separation area comprises a plurality of quantitative electrodes which are mutually spaced, and the RPA product in the quantitative liquid separation area is quantitatively controlled by controlling the on-off of the quantitative electrodes. The RPA and CRISPR reaction efficiency is high, and the result can be quickly obtained on the premise of ensuring high sensitivity and high specificity.

A microfluidic device includes first and second substrate structures. The first substrate structure has a first substrate surface configured to receive one or more droplets. A plurality of electrodes configured to apply an electric field to the droplets. The second substrate structure has a second substrate surface facing the first substrate surface and spaced apart from the first substrate surface to form a fluid channel. The microfluidic device has a first heating element adjacent to the first substrate structure and disposed on an opposite side of the first substrate surface, and a second heating element adjacent to the second substrate structure and disposed on an opposite side of the second substrate surface. The microfluidic device further includes one or more temperature sensors disposed adjacent to the fluid channel between the first substrate structure and the second substrate structure.

The application discloses an integrated digital microfluidic plasmonic metasurface chip biological image detection system, and belongs to the field of microfluidic and metasurface biological image sensing. The system comprises a digital microfluidic chip, a plasmonic metasurface chip, a light source, a CMOS image sensor and a control circuit. The digital microfluidic chip is provided with a driving electrode array, a medium layer and a hydrophobic layer, and is used for constructing a liquid path and controlling droplets. The plasmonic metasurface chip is combined with the digital microfluidic chip to form a detection site, and is used for detecting biomolecules by using a plasmonic resonance effect. The light source is used for exciting plasmonic resonance. The CMOS image sensor is used for capturing images at the detection site. The control circuit is used for controlling electrodes of the digital microfluidic chip, and realizes construction of the liquid path and control of the droplets. The biomolecule solution to be detected can be accurately guided to the detection site of the plasmonic metasurface chip, the light source is used for exciting plasmonic resonance, and the CMOS image sensor is used for capturing images. Image intensity changes are analyzed by using image processing software, and a detection result of the biomolecules is obtained.

The application belongs to the technical field of digital microfluidics, and discloses a high-throughput digital microfluidic chip based on a PCB, a driving system and a preparation method.The chip comprises a driving electrode substrate and a lower substrate.The driving electrode substrate provides a flat contact surface for micro-droplet movement, reduces micro-droplet movement resistance and residue and adhesion on the chip surface, the gap between adjacent driving electrodes is less than or equal to 100 microns, and the driving voltage for micro-droplet control is reduced.The lower substrate controls vertical addressing of the electrodes on the bonded driving electrode substrate, and on the basis of ensuring the electrode contact gap and flatness, a portable digital microfluidic chip with any large throughput can be manufactured at low cost.Based on the high scalability of active circuits and PCB chips, tens of thousands of discrete droplets can be driven in parallel on the same chip.By changing the chemical and biological components in the micro-droplets, the application can perform high-throughput analysis and synthesis tasks in chemical, biological and medical engineering applications.

The invention belongs to the related technical field of digital microfluidics, and discloses a digital microfluidics MALBAC device based on temperature measurement and control, which comprises a digital microfluidics chip 10 and a temperature measurement and control system 20, the digital micro-fluidic chip 10 adopts a closed structure and comprises an upper cover plate 111 and a lower chip 112 which are arranged in parallel relatively, and the temperature measurement and control system 20 comprises a temperature conduction module 21 and a temperature sensing module 22; according to the device, a totally-closed operation environment is provided for the MALBAC process, the risk of cross contamination is effectively avoided, the device can create a plurality of independent temperature areas on a single chip, the thermal cycle efficiency in the MALBAC technology is optimized, it is ensured that the temperature requirement of each stage in the amplification process is accurately met, and the amplification efficiency is improved. The integration level, the operation flexibility and the expandability of the device are greatly improved, so that the device can adapt to library construction requirements of various genetic material samples.

The present disclosure relates to a digital microfluidics, 'DMF', system and a method for operating the same. The DMF system comprises: a first substrate unit comprising a first substrate having arranged thereon a plurality of electrodes for manipulation of a liquid volume; and a second substrate unit spaced apart from the first substrate unit in a first direction, wherein the second substrate unit comprises a second substrate having arranged thereon an organic electrochemical transistor, 'OECT', biosensor.

The invention discloses an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing. The platform can be widely applied to the fields of regenerative medicine, drug research and development, disease research and the like. According to the platform, in-situ packaging and dynamic culture of the organoid are achieved through an electro-infiltration chip, the morphology and mechanical properties of the organoid are fed back in real time in combination with a holographic microscopy technology, and high-precision hardness gradient control is achieved through a photocuring printing system; after the organoid is formed, the platform can continue to observe the state of the organoid in situ through the digital holographic microscopy system, and specified drugs are conveyed through digital microfluidics. The platform comprises an electro-infiltration chip module, a digital holographic microscopy system, a photocuring biological three-dimensional printing system, a driving control unit and a data analysis processing unit, and supports parallel manufacturing, targeted drug delivery and high-throughput screening of organoids.

This invention discloses an experimental droplet routing method for digital microfluidic chips based on an improved A* algorithm. The improvement to the A* algorithm includes: incorporating the number of electrode wear cycles into the heuristic function of the A* algorithm; adding a coefficient related to the number of wear cycles, which can be modified according to the chip wear level; reducing the coefficient when chip wear is minor, prioritizing routing distance, and calculating the shortest distance as the target for route calculation; increasing the coefficient when chip wear is severe, aiming to calculate the route through areas of less worn chip and avoiding areas of severe wear; and adjusting the path after obtaining the droplet routing path, moving the repetitive wear areas at the start and end points to the middle of the path to reduce repeated wear on electrodes in the start and end areas. This invention, by improving the A* algorithm, allows droplet routing to consider electrode wear factors simultaneously, further improving the chip wear uniformity and extending the chip's lifespan.

The present application relates to the technical field of microfluidics, and provides a digital microfluidic chip, which comprises an electrode array, a driving module and a top cover arranged above the electrode array, a gap for accommodating small droplets is formed between the top cover and the electrode array, the electrode array comprises a plurality of rows of electrode array groups, each row of the electrode array groups comprises a plurality of electrodes, the driving module controls each electrode in each row of the electrode array groups to be opened in turn, and the size of the small droplets is regulated by adjusting the gap and the electrodes in the electrode array. A pixel driving method of the digital microfluidic chip is also provided. A constant temperature amplification method is also provided, which adopts the pixel driving method of the digital microfluidic chip. The GOA and MUX circuit combination design is adopted, the driving signal complexity of the electrode matrix can be greatly reduced, the stability is improved, and simple and flexible electrode driving is achieved.

This invention relates to an integrated surface acoustic wave (SAW) device, system, and method for digital microfluidic control of droplet rotation and centrifugal manipulation. The device includes a digital microfluidic region, a SAW processing region, and a droplet transition interface region located between the two. A droplet residence area is provided within the SAW processing region. After sample introduction, transport, splitting, fusion, or temporary storage within the digital microfluidic region, the droplet enters the droplet residence area via the droplet transition interface region, where it forms a rotating flow, a circulating flow, and local enrichment under the influence of an asymmetric acoustic field. After enrichment or mixing, bright-field, dark-field, or fluorescence detection can be performed using an in-situ optical detection module. After processing, the droplet returns to the digital microfluidic region for continued transport, collection, or disposal. This solution improves the continuity, automation, and on-chip integration of droplet cross-region manipulation.