An integrated semiconductor device for manipulating and processing bio-entity samples and methods are described. The device includes a lower substrate, at least one optical signal conduit disposed on the lower substrate, at least one cap bonding pad disposed on the lower substrate, a cap configured to form a capped area, and disposed on the at least one cap bonding pad, a fluidic channel, wherein a first side of the fluidic channel is formed on the lower substrate and a second side of the fluidic channel is formed on the cap, a photosensor array coupled to sensor control circuitry, and logic circuitry coupled to the fluidic control circuitry, and the sensor control circuitry.

The disclosed embodiments generally relate to a method and system to synthesize a target molecule within a droplet. In an exemplary embodiment, a first microfluidic device configured to contact a polynucleotide-containing component from a sample with lysis reagents to form a first droplet. The lysis reagents include an enzyme having protease activity. The first droplet is encapsulated with an immiscible carrier fluid. A collection reservoir is provided to receive and incubate the first droplet for a first duration of time. The first duration of time is sufficient to inactivate the enzyme of the lysis reagent. A second microfluidic device is provided to receive the first droplet and add nucleic acid synthesis reagent to thereby form a second nucleic acid synthesis droplet in the immiscible carrier fluid. Finally, a reaction chamber is provided to synthesize the target polynucleotide within the second nucleic acid synthesis droplet.

Microfluidic pumps are provided that use electrowetting to manipulate the location of one or more droplets of a working fluid (e.g., water) in order to pump tears, blood, laboratory samples, carrier fluid, or some other payload fluid. The working fluid is separated from the payload fluid by one or more droplets of an isolating fluid that is immiscible with the working fluid. The working fluid is manipulated via electrowetting, by applying voltages to two or more electrodes, to repeatedly move back and forth. Forces, pressures, and/or fluid flows exerted by the working fluid are coupled to the payload fluid via the droplet(s) of isolation fluid and reed valves, diffuser nozzles, or other varieties of valve can act as flow-rectifying elements to convert the coupled forces into a net flow of the payload fluid through the pump.

The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc. of a first fluid being urged into and/or out of a second fluid can be controlled by controlling various properties of the fluid and/or a fluidic droplet, for example curvature of the fluidic droplet, and/or controlling the applied electric field.

Provided herein are methods of splitting droplets containing magnetically responsive beads in a droplet actuator. A droplet actuator having a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at the droplet operations electrodes, is provided. The magnetically responsive beads in the droplet are immobilized using the magnetic field and the plurality of droplet operations electrodes are used to split the droplet into first and second droplets while the magnetically responsive beads remain substantially immobilized.

An integrated semiconductor device for manipulating and processing bio-entity samples and methods are described. The device includes a lower substrate, at least one optical signal conduit disposed on the lower substrate, at least one cap bonding pad disposed on the lower substrate, a cap configured to form a capped area, and disposed on the at least one cap bonding pad, a fluidic channel, wherein a first side of the fluidic channel is formed on the lower substrate and a second side of the fluidic channel is formed on the cap, a photosensor array coupled to sensor control circuitry, and logic circuitry coupled to the fluidic control circuitry, and the sensor control circuitry.

A new simple transfection method using an integrated electrowetting nano-injector (INENI) with controlled dosage delivery and high transfection efficiency is disclosed. The volume of delivery can be controlled via voltage application to an inner and outer electrode integrated into a nano-pipette. With higher voltages, more liquid enters the INENI and with lower voltages liquid is expelled. This method can be used to deliver plasmid DNA directly into the nuclei of cells. The INENI requires only the use of a single probe since both electrodes are integrated into the same nano-pipette. Hence, more space is available, and ergo the INENI offers a simplistic means for direct injection of metered amounts of exogenous material into the confines of a cell cytoplasm and/or nucleus while retaining full cell viability.

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

Provided herein are methods of splitting droplets containing magnetically responsive beads in a droplet actuator. A droplet actuator having a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at the droplet operations electrodes, is provided. The magnetically responsive beads in the droplet are immobilized using the magnetic field and the plurality of droplet operations electrodes are used to split the droplet into first and second droplets while the magnetically responsive beads remain substantially immobilized.

An electrowetting panel includes a base substrate; an electrode array layer, including a plurality of electrodes arranged into an array; an insulating hydrophobic layer; a microfluidic channel layer located on the base substrate. Each electrode of the plurality of electrodes is connected to a driving circuit, and a droplet can move along a first direction by applying an electric voltage on each electrode. The insulating hydrophobic layer is located on the electrode array layer, and the microfluidic channel layer is located on the insulating hydrophobic layer. The electrodes includes a plurality of driving electrodes and a plurality of detecting electrodes. Along the first direction, a number N of the driving electrodes is located between every two adjacent detecting electrodes, where N is a natural number. The electrowetting panel also includes a detecting chip electrically connected to the detecting electrodes.