The present invention relates to fluidic devices, especially microfluidic devices, for aliquoting and pairwise combinatorial mixing of a first set of liquids with a second set of liquids. The device architecture is designed to move liquids in two separate phases, a first phase where the liquids are exposed to a first directional force field to move the liquids in a first direction, from a reservoir to aliquot chambers, and a second phase where the liquids are exposed to a second directional force field to move the liquids in a second direction, from the aliquot chambers to the mixing chambers. The first and second directional force fields that the device is exposed to may be achieved using a single directional force field (i.e. a rotor driven centrifugal force field) and by re-orienting the position of the device with respect to the centrifugal forces between the first and second phases of operation. The device architecture comprises reservoirs for each of the first fluids and reservoirs for each of the second fluids. Each reservoir is fluidically connected to aliquoting chambers, either arranged in parallel or in series, for providing aliquots of the fluid which may be metered. The conduits providing fluid communication between the reservoirs and aliquoting chambers are arranged in a first direction. A series of mixing chambers is also provided, and each mixing chamber is fluidically connected to one aliquot chamber for a first liquid and one aliquoting chamber for a second liquid. The conduits providing fluid communication between the aliquoting chambers and mixing chambers are arranged in a second direction.

The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion. The invention is particularly advantageous in apparatus for performing sensitive multistep reactions, such as pH-based DNA sequencing reactions.

An apparatus for optically-verified de novo DNA synthesis includes a microfluidic system that has channels leading in and out of a synthesis chamber having a functionalized region on a floor thereof on which a single-strand of DNA to which a nucleotide is to be attached can be fixed. The chamber is in optical communication with both an illumination system, which excites an electron in a fluorophore that is attached to the DNA strand, a detection system, which detects a signature photon emitted as the excited electron decays into its ground state.

The invention features methods of making devices, or platens, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.

A flow control device, a system and a method are disclosed. The flow control device comprises a displaceable means (101) having a direction of displacement and being displaceable between a first position and a second position. The flow control device further comprises a body (110) comprising a first cavity (102) in fluid contact with a first side of the displaceable means (102) forming a first volume. The first cavity further comprising a first inlet (103), a primary outlet (104) with a primary flow resistance and arranged essentially parallel with the displacement direction, wherein the primary outlet comprises an inlet opening (105) facing the displaceable means at a first distance (106) from the displaceable means in the direction of displacement, a secondary outlet (107) with a secondary flow resistance, wherein the displaceable means is displaceable between a first position and a second position. In the first position, a first fluid path (108) between the first inlet (103) and the primary outlet (104) is provided, and a second flow path (109) between the inlet (103) and the secondary outlet (107) is provided; In the second position, the displaceable means is displaced at least the first distance and close the inlet opening (105) of the primary outlet, whereby the inlet opening (105) is blocked, and the second fluid path (109) between the first inlet (103) and the secondary outlet (107) is maintained.

In a novel process for methanol production from low quality synthesis gas, in which relatively smaller adiabatic reactors can be operated more efficiently, some of the inherent disadvantages of adiabatic reactors for methanol production are avoided. This is done by controlling the outlet temperature in the pre-converter by rapid adjustment of the recycle gas, i.e. by manipulating the gas hourly space velocity in the pre-converter.

The invention relates to a flow element for transferring fluids comprising a capillary cartridge (1) having an integrated capillary line (3). The capillary cartridge according to the invention (1) has a ring-shaped channel (8) and securing grooves (6, 6), wherein the flow element is characterized in that the capillary line (3) is arranged in the ring-shaped channel (8). The ends of the capillary lines (3) are connected to connection elements (9) in which securing grooves (6, 6) are secured in a positive locking manner. The flow elements according to the invention contribute toward improved manageability and effectiveness of components. In a preferred embodiment, the flow elements are used as a distribution system in the form of a plurality of capillary cartridges (1-1, 1-2, . . . ). Such distribution systems are of technical importance in the field of catalyst testing apparatuses with reactors arranged in parallel.

The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion.

A device for the microstructured grafting of proteins onto a substrate, comprising a substrate (7), a layer comprising a polyethylene glycol and being placed on the substrate, a matrix (10) of micromirrors for propagating the light in a first pattern and for replacing the first pattern with a second pattern. The microfluidic circuit is filled so as to bring a first aqueous solution containing a first protein into contact with the layer, a first microstructured image of the first pattern being formed on the layer to photoprint the first protein on the layer, and the microfluidic circuit is adapted to replace the first aqueous solution with a second aqueous solution containing a second protein so as to bring the second aqueous solution and the layer into contact, the first pattern being replaced with the second pattern in order to photoprint the second protein on the layer.

An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.