191 results about "Microfluidic channel" patented technology

The present invention relates to a microfluidic device (1) for forming a cell aggregate comprising at least one first cell (C1) and one second cell (C2), and for individually processing selected cells of the cell aggregate: - Microfluidic channel (10); - At least one main inlet (11) for fluids containing a first cell, a second cell, and a third cell, respectively, located in the first portion (101) of the microfluidic channel; - An outlet (12) located in the second portion (102) of the microfluidic channel for controlling the flow rate of fluid within the microfluidic channel; - A first auxiliary inlet (131) for at least one first auxiliary fluid, located in the first portion (101) of the microfluidic channel upstream or downstream of the main inlet (11); - At least one cell trapping section (14) positioned between the first and second parts within the microfluidic channel; - At least one first valve to control the flow rate of the first auxiliary fluid, causing the fluid containing the first cells and the second cells to flow at a predetermined height within the microfluidic channel, thereby guiding the first cells and the second cells to the first and second capture units, respectively. Equipped with, The microfluidic device relates to a microfluidic device in which each cell capture section (14) comprises at least one first capture section (141) and one second capture section (142), each first and second capture section being sized to accommodate a first or second cell, the first and second capture sections being adjacent to each other in a direction perpendicular to the bottom (100) of the microfluidic channel, and forming a cell aggregate containing the captured first and second cells, each cell being at a different height relative to the bottom of the microfluidic channel.

An apparatus may include a microfluidic chip including at least one microfluidic channel and a first at least one electrical interconnect. An apparatus may include a circuit board having at least one interface interconnect and a second at least one electrical interconnect electrically coupled with the first at least one electrical interconnect of the microfluidic chip. An apparatus may include a cartridge enclosing the microfluidic chip and the circuit board, the cartridge including at least one opening allowing access to the at least one microfluidic channel on the microfluidic chip and the at least one interface interconnect.

The invention relates to a blood rheological parameter online monitoring and thrombus risk assessment method, which comprises the following steps: introducing a blood sample into a microfluidic channel with a periodic geometric mutation structure, applying unsteady shear disturbance through a piezoelectric oscillation device, inducing blood to enter a non-equilibrium rheological state, and exciting a microcosmic coagulation tendency; the red blood cell aggregation behavior, the cell layer slippage phenomenon and the plasma shearing stability are recognized through the photo-thermal interference technology, and the rheological structure layer differentiation characteristics in blood are obtained; the blood subjected to shear disturbance is guided to a micro-channel high-pressure area provided with a flow-limiting threshold structure, and pressure mutation and microcoacervation nucleation generation behaviors induced by local stress disturbance are detected through a nanoscale piezoresistive sensor so as to identify sub-phase change response characteristics of the blood; and constructing a rheological instability index system on the basis of physical response signals obtained by shear disturbance, slippage and variable response, and when linkage abnormity of any two indexes is detected, judging that a high-risk event of thrombosis occurs and outputting a risk prompt signal.

The invention discloses a microfluidic sorting chip and method based on the synergistic effect of multistage surface acoustic waves and sheath flow. The chip comprises a piezoelectric substrate; the PDMS micro-fluidic channel comprises a sample inlet, a sheath flow inlet, a sorting main flow channel for sorting microorganisms, and a collecting unit arranged at the tail end of the sorting main flow channel; the sheath flow inlet is converged from two sides of the sorting main flow channel through two flow paths, and forms hydrodynamic focusing with sample liquid conveyed by the sample inlet in the sorting main flow channel; the number of the multi-stage IDT arrays is four, every two of the multi-stage IDT arrays are symmetrically distributed along the two sides of the sorting main flow channel, the working frequency of the multi-stage IDT arrays is 100-150MHz, and the multi-stage IDT arrays are used for generating a superposition sound field with high energy density. According to the invention, four groups of high-frequency IDT arrays are used for generating a superposed sound field, and a PDMS sorting channel and a double-channel sheath flow system are combined, so that the sorting problem of microorganisms with acoustic contrast factors smaller than 0 is solved.

The present disclosure generally relates to microfluidics, and to systems and methods for controlling the introduction of fluids. For example, certain aspects are generally directed to microfluidic devices having ports able to direct the end of a pipette tip into an end portion that is sized so as to allow fluid to flow from the pipette tip into an exit fluidly connected to a microfluidic channel. For example, the port may have a tapered portion that directs the pipette tip to the end portion. The end portion may be sized such that it is difficult for fluid to backflush around the pipette tip, and thus, the fluid is able to flow into microfluidic channels within the device, e.g., without resulting in excessive fluid remaining within the end portion. Other aspects are generally directed to methods of making or using such microfluidic devices, kits including such microfluidic devices, and the like.

The invention relates to a microfluidic component used for electrical impedance measurement through a biological object (O), said microfluidic component comprising: A support in which is made a main microfluidic channel (C_1) defining a path for the circulation of a fluid containing the biological object (O), A trapping device positioned in the main microfluidic channel (C_1) on the circulation path of said biological object, At least one first electrode and a second electrode intended to be each set at a distinct electrical potential, in order to perform said impedance measurement, Said trapping device being composed of at least one first central pillar (P_1) and a second central pillar (P_2) positioned inside the microfluidic channel, The first central pillar being configured to form the first electrode and the second central pillar being configured to form the second electrode.Figure to be published with the abbreviation: Figure 2.

A microfluidic system for controlling movement of charged particles, including a microfluidic channel, at least three electrodes, a plurality of conductor leads and at least two drive power supplies. Each electrode is in electrical contact with the electrolyte, and a pseudo-capacitance, a double-layer capacitance or a combination thereof is formed at an electrode-electrolyte interface. Each drive power supply periodically produces a voltage or current excitation, and is connected to one or more electrodes via the conductor leads. Each electrode continuously undergoes charging-discharging alternating cycles to form a traveling-wave electric field in the microfluidic channel. A maximum charge capacity of each electrode is greater than a total amount of charges transferred thereon during a charging or discharging process. A control method based on the microfluidic system is also provided.

The application discloses a hemolysis analyzer based on an integrated optical waveguide sensor and a preparation method thereof, and comprises an integrated photon waveguide, a nano filter and a micro-fluidic channel, wherein the integrated photon waveguide is a single waveguide with a middle spiral type and coupling gratings on both sides. The hemolysis analyzer fully utilizes the advantages of high sensitivity and small volume of the integrated optical waveguide sensor, and realizes sample-free preparation by combining the methods of instantaneous absorption and hemoglobin filtration, and can quickly and accurately detect hemolysis and the degree of hemolysis.

The invention relates to the technical field of collagen intelligent monitoring, and particularly discloses an intelligent collagen monitoring method and system integrated with a microsensor. Enzyme response hydrogel with switchable states is anchored to the skin through a microneedle array, a high-frequency acoustic impedance analysis module is used for continuously probing the acoustic impedance change of the hydrogel, and the collagen monitoring accuracy is improved. Identifying a collagen degradation event; once collagen degradation is detected, the system activates the micro-regeneration unit, a cleaning solution and a regeneration solution are conveyed through a microfluidic channel, a broken peptide chain is removed, a hydrogel cross-linked network is reconstructed, and functional regeneration of the sensing unit is realized; the system further comprises a regeneration state confirmation and cycle reset mechanism, and the reliability of each monitoring cycle and the consistency of data references are ensured. According to the method, the limitation of a traditional monitoring method is overcome, multiple times of recycling of a single sensor is achieved, the credibility and consistency of long-term monitoring data are improved, and the method has important significance on skin health management and senescence research.

The invention discloses an octopus bionic sucker flexible negative voltage electrode patch for nerve electrical regulation and control. The octopus bionic sucker flexible negative voltage electrode patch comprises a flexible substrate, an octopus bionic sucker array and a microneedle electrode array, a patterned micro-fluidic channel is arranged in the flexible substrate, and a first micro-fluidic hole array is arranged on the surface of the flexible substrate; the octopus bionic suction cup array has flexibility and adhesion and comprises a suction cup array, an electrode hole array arranged on the suction cup array and a second micro-fluidic hole array, and the second micro-fluidic hole array and the first micro-fluidic hole array correspondingly form a micropore channel; the microneedle electrode array is inserted into the electrode hole array; when the electrode patch is used for nerve electric regulation and control, under the action of pre-tightening force, the suction cup adheres to the skin and is preliminarily attached to the skin, the micro-needle electrode array on the suction cup acts on the cortex, gas in the suction cup is extracted through the micro-fluidic channel and the micropore channel to obtain an external negative pressure source, stable adsorption force is provided through negative pressure, sweat on the surface of the human body is discharged, and therefore the skin can be absorbed. And long-term high-quality nerve electric regulation and control are realized.

The application provides a method for synthesizing benzimidazole Michael addition derivatives in a continuous flow reactor, and 2-methylbenzimidazole and alpha, beta-unsaturated olefins are used to catalyze the online synthesis of benzimidazole Michael addition derivatives in a microfluidic channel reactor by using a lipase Lipozyme RM IM. The method not only greatly shortens the reaction time, but also has high conversion rate; meanwhile, the Michael addition reaction of 2-methylbenzimidazole and alpha, beta-unsaturated olefins is catalyzed by using the economical lipase Lipozyme RM IM in methanol, the reaction cost is reduced, the post-processing step is simplified, and the method has the advantages of green environmental protection, economy and efficiency.

The present application relates to a kind of hundred nanometer level particle sorting manipulation chip, device and sorting manipulation method, the chip includes microlens, microfluidic channel, sorting outlet and sorting inlet, the sorting outlet is bifurcation, the sorting inlet is trifurcation, including sample flow inlet and 2 focus flow inlets;Sorting inlet and sorting outlet are respectively arranged at the two ends of microfluidic channel, and microlens is arranged at the intersection of 2 sorting outlets.The device includes chip, light source, injection device and observation platform, and the light emitted by light source is irradiated into microfluidic channel through microlens, and light force is applied to the particle in the fluid to be sorted, and different size particles enter different sorting outlets, finally realize sorting.Compared with prior art, the present application can realize the rapid sorting of hundred nanometer level particle, with the advantages of high sorting efficiency, high control precision, etc., and has important application value for the sorting and manipulation of micro-nano scale particles such as virus and bacteria.

This invention relates to the field of biomedical technology, specifically to a microfluidic channel, a microfluidic chip, and their applications for squeezing cells. The microfluidic channel is composed of several continuously arranged cell squeezing units. Each cell squeezing unit consists of a main channel and a squeezing region. The main channel is composed of connecting sections and curved sections. The squeezing region includes a first squeezing section, a squeezing slit, and a second squeezing section. The width of the first squeezing section gradually decreases from the main channel, reaching its minimum at the squeezing slit, and then gradually increases towards the second squeezing section until it matches the width of the main channel. The squeezing slit is rectangular, with a width of 4-10 μm and a length of 20-60 μm. The microfluidic channel provided by this invention applies relatively uniform and dispersed mechanical stress to the cell membrane, reducing cell breakage and mortality rates, and allowing cells to restore their integrity through the cell membrane's self-repair mechanism after squeezing.

Three-dimensionally (3D) printed, wearable, electronic sensing articles and methods of manufacture are disclosed. In one example embodiment, the present disclosure provides A wearable article that includes a three-dimensionally printed base, wherein the base of the article comprises a three-dimensionally printed mesh which is formed of an elastomeric polymer composition. The wearable article also includes a microfluidic channel coupled to the mesh, the microfluidic channel having an inlet and an outlet disposed at opposite ends of the channel, wherein the microfluidic channel is curved in a form of a serpentine shape; and wherein the serpentine shape is provided by a plurality of 180-degree semi-circular segments.

The application provides an electrochemical sensing ELISA reagent card, comprising a microfluidic channel body and an electrochemical sensor body which are bonded together, wherein: a plurality of "annular" liquid flow channels are arranged on the microfluidic channel body, each "annular" liquid flow channel is formed by a working electrode covering flow channel and a counter electrode and a reference electrode covering flow channel in series, and the "annular" liquid flow channels are communicated through a common flow channel; the electrochemical sensor body comprises a flat plate substrate and a plurality of screen-printed electrodes which are printed in parallel on the flat plate substrate, and each screen-printed electrode comprises a working electrode, a counter electrode and a reference electrode. The electrochemical sensing ELISA reagent card combines an electrochemical biosensor and a microfluidic chip, and solves the technical problems of large sample / reagent consumption, single detection index and liquid volume influence on absorbance measurement of a traditional ELISA reagent kit.

The application provides an organ chip, which comprises, from top to bottom, a liquid collecting layer (1), a pressing layer (2), a glue injection layer (3), a tissue layer (4), a film layer (5) and an oxygen control layer (6). The application provides a novel organ chip, which comprises a film layer and an oxygen control layer, is used for making oxygen pass through the film layer and be eliminated by an oxygen absorbent in the oxygen control layer, liquid cannot pass through the film layer, so that the liquid circulates or is supplemented in the microfluidic channel, and the oxygen concentration in the culture solution is made to be closer to the real physiological environment in the human body based on the cavity and the through structure formed by laminating and sealing of the layers. In addition, a plurality of molds are arranged, so that a plurality of cell models can be simultaneously cultured, and a high-throughput culture effect is realized.

A method of alignment and fusion of cells with an electrical field includes firing a first fluid dispenser of an electrofusion device until a first impedance sensor in a first microfluidic channel of the electrofusion device detects a presence of a first cell. The method includes firing a second fluid dispenser of the electrofusion device until a second impedance sensor in a second microfluidic channel of the electrofusion device detects a presence of a second cell. The method includes moving the first cell and the second cell into a merging chamber of the electrofusion device by firing a third fluid dispenser of the electrofusion device, in response to alignment of the first cell in the first microfluidic channel with the second cell in the second microfluidic channel. The method further includes fusing the first cell and the second cell in the merging chamber by creating an electrical field in the merging chamber.

The present invention relates to a microfluidic synthesis chip cartridge on which a synthesis chip including a microfluidic chamber formed in a predetermined shape is mounted, so that two or more fluids that do not mix well with each other are uniformly mixed to generate a synthesized sample. The purpose of the present invention is to provides a microfluidic synthesis chip cartridge wherein: the microfluidic synthesis chip cartridge includes a plate-shaped member on which two or more synthesis chips having microfluidic channels of a predetermined shape for mixing or reacting two or more liquid samples are mounted in parallel, thereby providing a structure and arrangement capable of dramatically increasing production per unit time despite the synthesis chips having microfluidic channels; and the raw-material supply timings of the two or more synthesis chips are aligned solely by changing the shapes of the microfluidic channels rather than by a separate electronically precise mechanism, thereby enabling synchronization among a plurality of synthesis chips with an inexpensive and simple structure.

The application discloses a soil ion concentration sensor suitable for a supergravity environment, which comprises, from top to bottom, a packaging layer, a pore water extraction filter membrane, a measuring layer and a substrate layer; the packaging layer is provided with a sampling window; the pore water extraction filter membrane is provided with a filter hole area completely overlapping with the sampling window; the top surface of the measuring layer is provided with a microfluidic channel in a groove type structure and a fluorescent optical fiber concentration sensor arranged in the microfluidic channel; and the main channel at the first end of the microfluidic channel overlaps with the filter hole area of the pore water extraction filter membrane. The application has the advantages of small volume, strong anti-electromagnetic interference ability, high g resistance and corrosion resistance, can be embedded in the soil pore environment for long-term stable work, and realizes in-situ detection of heavy metal ion concentration through the fluorescent optical fiber concentration sensor.

A method, comprising: determining electrophoretic mobility associated with a particle in a transverse alternating force microfluidic channel; determining a size of the particle based at least in part on one of Brownian motion of a particle or one or more images of the particle. A system comprising: a microfluidic channel; a plurality of electrodes oriented transverse to the microfluidic channel, the plurality of electrodes comprising an alternating electric field; and a classification system configured to: determine one or more of the following: an electrophoretic mobility associated with a particle in the transverse AC microfluidic channel and / or determine, based at least in part on the electrophoretic motion, and size from image analysis or Brownian motion of a particle or one or more images of the particle, particle shape, particle deformability, for recognition of surface characteristics, such as assaying for receptors and ligands, and to perform electroporation.

The invention provides an on-chip optical sensor for medical detection and a manufacturing method thereof, and relates to the technical field of on-chip optical sensors. According to the scheme, the device mainly comprises a substrate, a double-peak waveguide interference structure, a near-infrared photoelectric detector and a micro-fluidic channel, the double-peak waveguide interference structure is arranged on the upper surface of the substrate, comprises a waveguide layer and is used for amplifying refractive index change and outputting an interference signal; the micro-fluidic channel and the near-infrared photoelectric detector are respectively arranged in a sensing area and an output area on the upper surface of the waveguide layer; recognition molecules are arranged in the micro-fluidic channel and are used for being specifically combined with target molecules of a medical sample and generating refractive index change; and the near-infrared photoelectric detector is used for reading the interference signal and converting the interference signal into an electric signal. According to the scheme, the machinable absorption layer is directly integrated in the evanescent field area of the double-peak waveguide, on-chip direct reading of waveguide interference signals is achieved, coupling loss is reduced, and the signal-to-noise ratio is remarkably increased.

The invention relates to an intelligent cell mechanical property analysis method driven by a cell queue flow mechanism, which comprises the following steps of: acquiring experimental group flow data generated when a cell queue flows in a micro-fluidic channel to realize non-intrusive and high-throughput experimental observation and data capture of cell individuals and group flow dynamics; and an experiment reference is provided for analysis. A cell queue fluid-solid coupling model is established, numerical simulation is carried out, multiple groups of simulation group flow data are obtained by changing mechanical parameter values, complex flow behaviors of a cell queue under various potential mechanical characteristics are efficiently and controllably simulated in a virtual environment, and a simulation database with sufficient samples is established. Experimental data of a queue to be tested are matched with simulation data in a three-dimensional simulation database, so that the complex flow performance of a sample to be tested is quickly compared with the simulation database of massive known cell types and mechanical parameters, complex modeling and parameter inversion processes are bypassed, and the most similar known type is directly positioned.

The application discloses a paper-based microfluidic intelligent wound monitoring bandage based on a laser-induced graphene electrode array and a preparation and signal processing method thereof. The bandage comprises a calcium alginate / zinc oxide antibacterial base, a wax-printed paper-based lateral chromatographic microfluidic channel layer, a CO2 laser direct writing LIG multifunctional electrode array, a colorimetric indication area, an NFC wireless communication module and a silver nanowire electrically controlled drug release module. The LIG electrode is fixed and modified by enzymes to detect uric acid, lactic acid, glucose and pH value respectively; the paper-based colorimetric disc detects bacterial protease and TNF-alpha; the NFC radio frequency field provides energy to realize battery-free operation. The built-in signal processing method comprises temperature compensation, cross interference elimination, multi-parameter fusion infection risk scoring and double-threshold closed-loop drug delivery decision. The preparation process mainly uses laser direct writing, screen printing and ion crosslinking, has low material cost and is green and environmentally friendly, and is suitable for closed-loop monitoring and treatment of chronic wounds at home and in clinic.

Microfluidic devices and methods for dissociating and manipulating cells or particles within a microfluidic channel are disclosed. The microfluidic device includes an inlet, an outlet, and a microfluidic channel arranged on a substrate between the inlet and the outlet. The microfluidic device includes a first set of piezoelectric actuators arranged adjacent to the inlet channel and configured to dissociate particles of a fluid sample within the microfluidic channel. The microfluidic device includes a second set of piezoelectric actuators arranged between the inlet and outlet channels and configured to manipulate particles of a fluid sample as particles move through the microfluidic channel. The microfluidic device includes a third set of piezoelectric actuators arranged above the outlet channel and adjacent to the outlet and configured to discharge a portion of the fluid sample from the microfluidic channel through the outlet.

The application discloses a self-driven disc type blood separation and detection device and method, which comprises a sample adding layer, a separation layer and a detection layer, and the layers are sequentially connected through screw fixation. The sample adding layer is provided with a sample adding port and a first screw hole; the separation layer comprises four repeated blood separation units and a second screw hole, and each separation unit comprises a sample inlet, a micro-fluidic channel, a filter groove, a sample outlet and a waste liquid collecting chamber; and the detection layer is provided with a screen-printed electrode interface and a third screw hole. Blood samples are dripped into the device from the sample adding port, and under the driving of the internal negative pressure of the device, the blood samples enter the micro-fluidic channel, and blood filtration is realized by using the gravity difference between blood cells and blood plasma. The filtered blood plasma flows into the detection layer and contacts with the screen-printed electrode detection unit, so that electrochemical detection is realized. The device does not need external power supply, thereby reducing sample operation, reducing the volume of the separation device, improving the blood separation efficiency, and facilitating instant detection and multi-channel detection of blood samples.

The invention provides a bionic targeted motion research method of a biological enzyme driven nano-robot. The method comprises the following steps: preparing an enzyme driven nano-robot; preparing a micro-fluidic chip, wherein the micro-fluidic chip is provided with an H-shaped micro-fluidic channel structure which is diluted layer by layer; determining motion characteristics and enzyme properties of the enzyme-driven robot in composite field environments such as a gradient substrate concentration field, an enzyme chemotactic agent field and a gradient viscosity field; a chemotactic factor solution, a solution containing the enzyme-driven nano-robot and a urea solution are injected into a middle channel of the micro-fluidic chip through an injection pump, and the chemotactic behavior and targeted movement of the robot in a fluid composite field are observed by controlling the fluid concentration and flow velocity and representing a chemotactic factor concentration gradient field in a stable flow state. According to the technical scheme provided by the invention, the chemotactic sensitivity of the bio-enzyme driven nano-robot to different types of chemotactic factors can be explored, and the chemotactic movement of ultralow-concentration chemical signal molecules is realized.

A biotechnological analysis module (1) comprises a reactor (2) and an assembly (10) consisting of a microfluidic system (11) and a photonic circuit (12). The photonic circuit (12), together with the microfluidic system (11), encloses a sample volume (14) which is connected to the reactor (2). The microfluidic system (11) comprises at least one microfluidic channel (13) which is connected to the sample volume (14) and / or the reactor (2). The photonic circuit (12) comprises an optical waveguide assembly (19) arranged on the enclosed sample volume (14) such that light from the optical waveguide assembly (19) can be coupled into the enclosed sample volume (14) and / or that light from the enclosed sample volume (14) can be coupled into the optical waveguide assembly (19).Additionally or alternatively, the optical waveguide arrangement (19) is arranged on the at least one microfluidic channel (13) such that light which can be transmitted via the optical waveguide arrangement (19) can be used to control the flow rate of the amount of fluid flowing in the at least one microfluidic channel (13).

The invention relates to a microfluidic component used for electrical impedance measurement through a biological object (O), said microfluidic component comprising: - A support in which is made a main microfluidic channel (C_1) defining a path for the circulation of a fluid containing the biological object (O), - A trapping device positioned in the main microfluidic channel (C_1) on the circulation path of said biological object, - At least one first electrode and a second electrode intended to be each brought to a distinct electrical potential, in order to perform said impedance measurement, - Said trapping device being composed of at least one first central pillar (P_1) and a second central pillar (P_2) positioned inside the microfluidic channel, - The first central pillar being configured to form the first electrode and the second central pillar being configured to form the second electrode.

Mixing a liquid sample and at least one reagent in microchannel of a microfluidic device includes preparing a segment of the liquid sample in contact with the reagent(s) within the microchannel. The liquid segment has a volume of 2 μL or less and defines a proximal gas-liquid interface and a distal liquid-gas interface. The gas of the proximal gas-liquid interface is in gaseous communication with a distal liquid-gas interface of another amount of liquid disposed proximally to the liquid segment within the microchannel of the microfluidic channel. The gas of the distal liquid-gas interface is disposed distally to the liquid segment within the microfluidic channel. With the liquid of the liquid segment in contact with the reagent(s) within the microchannel, the gas of the distal liquid-gas interface and / or the gas of the proximal gas-liquid interface is / are oscillated at an acoustic frequency to induce mixing of the liquid and the reagent(s).

The application discloses a sweat detection device based on one-way liquid discharge composite paper-based fiber membrane and a preparation method, and relates to the technical field of sweat detection. The preparation method is as follows: SEBS is dissolved and then added into LiCl aqueous solution to prepare an electrospinning liquid, and the composite paper-based fiber membrane is prepared on a hydrophilic paper base layer through electrospinning; a microfluidic channel is written on the hydrophilic side of the composite paper-based fiber membrane; a bromocresol green aqueous solution is added into the microfluidic channel and dried to obtain a pH detection module; a mixed solution of ferric chloride and potassium ferricyanide is added into the microfluidic channel, a mixed solution of chitosan and sodium alginate is added after drying, and lactic acid oxidase or glucose oxidase is added, and a color developing agent is added after drying to obtain a lactic acid detection module and a glucose detection module respectively; the detection device has the characteristics of simple structure, convenient operation, high detection accuracy and good color developing effect, and can realize colorimetric detection of pH, lactic acid and glucose without cross interference.