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.

Various embodiments of the teachings relate to a system or method for sample preparation or analysis in biochemical or molecular biology procedures. The sample preparation can involve small volume processed in discrete portions or segments or slugs, herein referred to as discrete volumes. A molecular biology procedure can be nucleic acid analysis. Nucleic acid analysis can be an integrated DNA amplification/DNA sequencing procedure.

Specially designed collection strips and their processing. By using specially designed collection strips, having a backer and one or more absorbent pads, in conjunction with a unique processing method, the processes of analyzing biological samples such as blood, or the like, may be done efficiency with the elimination of cross contamination risk. Identification of the sample stays with the sample throughout the process as it resides on the collection strip. The strip absorbs a known volume. The sample with identification is placed directly in an elution solution, without mechanically separating the sample from its identification information. Elimination of the need for mechanical separation tends to reduce cross contamination, as well as reducing sample processing time.

A system for processing a biological sample includes a substrate comprising a plurality of wells and a plurality of flow channels. The system further includes a flow control system comprising a manifold having a plurality of ports configured to fluidically couple to the plurality of wells, and one or more containment structures configured to contain carrier fluid and fluidically couple to the ports. The flow control system further includes a cradle configured to removably receive the substrate. The flow control system is configured to transmit pressure differential, via the manifold, to the plurality of wells so as to cause a plurality of sample volumes held by at least some wells of the plurality of wells to flow through respective flow channels and cause the carrier fluid to flow through the flow channels and form a plurality of droplets of the plurality of sample volumes separated by the carrier fluid.

A method for forming discrete volumes of aqueous fluid may comprise flowing aqueous fluid into a first conduit from a supply of aqueous fluid and flowing into the first conduit a spacing liquid supplied from a second conduit, the spacing liquid being immiscible with the aqueous fluid. The flowing of the aqueous fluid and the spacing liquid into the first conduit forms discrete volumes of the aqueous fluid, with consecutive discrete volumes of the aqueous fluid separated by the spacing liquid. The method may further comprise transferring the discrete volumes of the aqueous fluid and spacing liquid from the first conduit to a third conduit for processing.

A system for processing a biological sample can include a droplet generation assembly comprising a plurality of first reservoirs configured to contain an aqueous sample and a plurality of second reservoirs configured to contain a carrier fluid immiscible with the aqueous sample. The plurality of first reservoirs and the plurality of second reservoirs can be arranged to be in respective flow communication in pairs of reservoirs comprising a first reservoir of the plurality of first reservoirs and a second reservoir of the plurality of second reservoirs constituting a plurality of pairs of reservoirs. The droplet generation assembly can further include a flow control system configured to control a pressure in the plurality of pairs of reservoirs so as to generate a flow of a series of volumes of the aqueous sample separated by the carrier fluid. The system can further include a thermocycling system.

An automated system is provided for performing slide processing operations on slides bearing biological samples. In one embodiment, the disclosed system includes a slide tray holding a plurality of slides in a substantially horizontal position and a workstation that receives the slide tray. In a particular embodiment, a workstation delivers a reagent to slide surfaces without substantial transfer of reagent (and reagent borne contaminants such as dislodged cells) from one slide to another. A method for automated processing of slides also is provided.

Microfluidic structures and methods for manipulating fluids and reactions are provided. Such structures and methods may involve positioning fluid samples, e.g., in the form of droplets, in a carrier fluid (e.g., an oil, which may be immiscible with the fluid sample) in predetermined regions in a microfluidic network. In some embodiments, positioning of the droplets can take place in the order in which they are introduced into the microfluidic network (e.g., sequentially) without significant physical contact between the droplets. Because of the little or no contact between the droplets, there may be little or no coalescence between the droplets. Accordingly, in some such embodiments, surfactants are not required in either the fluid sample or the carrier fluid to prevent coalescence of the droplets. Structures and methods described herein also enable droplets to be removed sequentially from the predetermined regions.

A centripetal microfluidic platform comprised of a microfluidics disc and a reader for testing LAL-reactive substances in fluid samples is provided. The microfluidic disc may comprise at least two testing areas wherein each testing area includes a reservoir portion for receiving at least one fluid sample. The disc may comprise a distribution network portion in fluid communication with the reservoir portion. Each distribution network portion may comprise a distribution network of at least four (4) channels, wherein each channel has a metering portion and at least one analysis chamber portion. The analysis chamber portion may comprise a mixing chamber for mixing samples and reagents and an optical chamber portion that is compatible with an optical reader. The metering portion may be sized to meter an aliquot of the fluid sample for analysis in the analysis chamber portion. At least one analysis chamber portion has at least one reagent isolated therein. The centripetal microfluidic platform further includes a reader for testing fluid samples within a microfluidic disc comprising an enclosure, an optical bench, a centripetal disc drive, and a controller. A method for testing at least one fluid sample for LAL-reactive substances is also provided.

A pierceable cap 11 may be used for containing sample specimens. The pierceable cap 11 may prevent escape of sample specimens before transfer with a transfer device 43. The pierceable cap 11 may fit over a vessel 21. An access port in the shell of the pierceable cap 11 may allow passage of a transfer device 43 through the pierceable cap 11. At least one frangible layer 215, 216 may be configured with cross slits 506 in a particular cross slit geometry. The cross slits 506 may contain an openable portion 644 or be covered by a thin membrane 645. The shell 610 and frangible layer(s) 215, 216 may be integrated into a one piece cap 601, or be separate components 634. The membrane on which the cross slits 506 are placed can be flat or contoured to guide the transfer device 43 to the cross slits 506.