A method and apparatus for nucleic acid synthesis. The method employs a device including at least one deprotection unit to carry out a step of deprotection, at least one coupling unit to carry out a step of coupling, at least one oxidation/thiolation unit to carry out a step of oxidation orthiolation, at least one capping unit to carry out a step of capping, and at least one washing unit to carry out a step of washing. A plurality of reaction vessels for nucleic acid synthesis are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence and at least two reaction vessels are simultaneously acted upon at several of the units in series.

Disclosed herein are formulations, substrates, and arrays for the synthesis of PNA chains and PNA-DNA chimera on microarrays. In some embodiments, the formulations include a photo-protective compound that shields any PNA monomers, PNA polymers, or PNA-DNA chimera already attached to a microarray from radiation exposure during the synthesis of the PNA or PNA-DNA chains. In some embodiments, substrates and arrays comprise a porous or a planar layer for synthesis and attachment of PNA or DNA monomers, or PNA or PNA-DNA polymers. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of PNA monomers or PNA polymers to a microarray substrate.

A chemical synthesis device includes a reaction vessel, a waste liquid tank and an intermediate container. A chemical is supplied to the reaction vessel. The waste liquid tank is configured to hold waste liquid discharged from the reaction vessel. The intermediate container has a smaller capacity than the waste liquid tank. The intermediate container is provided between the reaction vessel and the waste liquid tank, via a waste liquid pipe. The pressure of the intermediate container is adjusted to adjust the flow supplied to the reaction vessel and the flow discharged from the reaction vessel.

In an example of the method, a functionalized coating layer is applied in depressions of a patterned flow cell substrate. The depressions are separated by interstitial regions. A primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions. A hydrogel is applied on at least the grafted functionalized coating layer.

In an example of the method, a functionalized coating layer is applied in depressions of a patterned flow cell substrate. The depressions are separated by interstitial regions. A primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions. A hydrogel is applied on at least the grafted functionalized coating layer.

Methods for the automated template-free synthesis of user-defined sequence controlled biopolymers using microfluidic devices are described. The methods facilitate simultaneous synthesis of up to thousands of uniquely addressed biopolymers from the controlled movement and combination of regents as fluid droplets using microfluidic and EWOD-based systems. In some forms, biopolymers including nucleic acids, peptides, carbohydrates, and lipids are synthesized from step-wise assembly of building blocks based on a user-defined sequence of droplet movements. In some forms, the methods synthesize uniquely addressed nucleic acids of up to 1,000 nucleotides in length. Methods for adding, removing and changing barcodes on biopolymers are also provided. Biopolymers synthesized according to the methods, and libraries and databases thereof are also described. Modified biopolymers, including chemically modified nucleotides and biopolymers conjugated to other molecules are described.

Health is a complex state that represents the continuously changing outcome of nearly all human activities and interactions. The invention provides efficient methods and arrays for health monitoring, diagnosis, treatment, and preventive care. The invention monitors a broad range of identifying molecules from a subject, such as circulating antibodies, and the invention evaluates a pattern of binding of those molecules to a peptide array. The characterization of the pattern of binding of such molecules to a peptide array with the methods of the invention provide a robust measure of a state of health of a subject.

A chemical synthesis device includes a reaction vessel, a waste liquid tank and an intermediate container. A chemical is supplied to the reaction vessel. The waste liquid tank is configured to hold waste liquid discharged from the reaction vessel. The intermediate container has a smaller capacity than the waste liquid tank. The intermediate container is provided between the reaction vessel and the waste liquid tank, via a waste liquid pipe. The pressure of the intermediate container is adjusted to adjust the flow supplied to the reaction vessel and the flow discharged from the reaction vessel.

In an example of the method, a functionalized coating layer is applied in depressions of a patterned flow cell substrate. The depressions are separated by interstitial regions. A primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions. A hydrogel is applied on at least the grafted functionalized coating layer.

In an example of the method, a functionalized coating layer is applied in depressions of a patterned flow cell substrate. The depressions are separated by interstitial regions. A primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions. A hydrogel is applied on at least the grafted functionalized coating layer.