Devices and methods for de novo synthesis of large and highly accurate libraries of oligonucleic acids are provided herein. Devices include structures having a main channel and microchannels, where the microchannels have a high surface area to volume ratio. Devices disclosed herein provide for de novo synthesis of oligonucleic acids having a low error rate.

Systems and methods are disclosed for enhancing the consistency of performance of assays, such as multiplexed assays, by printing features in a particular pattern, such that the outer edge of the pattern has a shape that is substantially similar to the shape of the test well. For example, the pattern is a ring pattern, such that the outer edge of the ring pattern is circular or oval along the bottom of multiplexed wells. The assay substrates prepared according to the methods described result in more accurate, precise, and sensitive chemical and/or biological analyses.

Supporting apparatus having a columnar first member and a cylindrical second member having an inner surface allowed to face with of an outer surface of the first member, one portion of the first member is inserted in a cylinder defined by the inner surface, a state of the members is allowed to change from a first state to a second state, the first state includes a state in which a predetermined space is ensured, the predetermined space is surrounded by one portion of the inner surface of the second member and an edge surface at one side of the first member that is different from the outer surface, the second state includes a state in which the second member has moved toward a side that is opposite to the one side relative to the first member from a base position of the members in the first state.

An array including a solid support having a plurality of contours along its exterior surface. A first subset of contours is positioned along the exterior surface of the solid support to form a first pattern of features and a second subset of contours is positioned along the exterior surface to form a second pattern of features. The contours of the first subset are juxtaposed with the second subset along the exterior surface, whereby the first and second patterns form an interleaved pattern. The features of the first pattern occur at a first elevation z.sub.1 and the features of the second pattern occur at a second elevation z.sub.2. The features of the first pattern are configured to attach analytes at a different elevation relative to analytes attached to the features of the second pattern.

Paper-based single cell arrays are provided, as well as methods of making and using the arrays. The invention provides a low cost, high-throughput platform to detect and quantify different types of DNA damage at point-of-care without expensive equipment or highly trained personnel. Ordinary paper can be covered with multiple layers of common printing ink and micro-patterned to form discrete and ordered arrays capable of binding a single cell, which are then lysed and imaged. The platform allows quick and inexpensive testing of multiple anti-cancer treatment options for a particular patient. The invention can make cancer treatment personalized and more effective, even in low-resource settings.

An apparatus (100) including multiple biological chips (110,120) includes a substrate (101), a first adhesive layer (134) disposed on the substrate (101), a first biological chip (110) and a second biological chip (120) disposed on the first adhesive layer (134) and attached to the substrate (101) by the adhesive layer (134). The apparatus (100) further includes a filler (130) disposed between the first biological chip (110) and the second biological chip (120). The filler (130) includes a second adhesive layer (135) extending between a side surface (114) of the first biological chip (110) and a side surface (124) of the second biological chip (120), the second adhesive layer (135) attaching the first biological chip (110) to the second biological chip (120). The filler (130) also includes a surface layer (132) disposed over the second adhesive layer (135). The surface layer (132) has a hydrophobic surface that is co-planar with a top surface (111) of the first biological chip (110) and a top surface (121) of the second biological chip (120).

A multiplexed sample plate comprising a sample well is disclosed. A plurality of substantially cylindrical reagent bead 2500 are inserted in use within a hole or aperture of the sample well. The substantially cylindrical reagent beads are positioned so as not to protrude beyond an upper surface of the base portion.

An electron microscopy grid, includes: (i) a perforated substrate, (ii) a support film on the perforated substrate, the support film having a thickness of 60 Å or less, and (iii) linkers attached on top of the support film. The linkers has at least one affinity group for immobilizing an analyte; wherein the linkers form a non-random pattern on the support film.

Defined sequence RNA synthesis by 3′.fwdarw.5′ direction is now well established and currently in use for synthesis and development of vast variety of therapeutic grade RNA and Si RNA etc. A number of such synthetic RNA requires a modification or labeling of 3′-end of an oligonucleotide. The synthesis of 3′-end modified RNA requiring lipophilic, long chain ligands or chromophores, using 3′.fwdarw.5′ synthesis methodology is challenging, requires corresponding solid support and generally results in low coupling efficiency and lower purity of the final oligonucleotide in general because of large amount of truncated sequences containing desired hydrophobic modification. We have approached this problem by developing reverse RNA monomer phosphoramidites for RNA synthesis in 5′.fwdarw.3′-direction. They lead to very clean oligonucleotide synthesis allowing for introduction of various modifications at the 3′-end.

An array including a solid support having a plurality of contours along its exterior surface. A first subset of contours is positioned along the exterior surface of the solid support to form a first pattern of features and a second subset of contours is positioned along the exterior surface to form a second pattern of features. The contours of the first subset are juxtaposed with the second subset along the exterior surface, whereby the first and second patterns form an interleaved pattern. The features of the first pattern occur at a first elevation z.sub.1 and the features of the second pattern occur at a second elevation z.sub.2. The features of the first pattern are configured to attach analytes at a different elevation relative to analytes attached to the features of the second pattern.