Methods and compositions are disclosed relating to the localization of nucleic acids to arrays such as silane-free arrays, and of sequencing the nucleic acids localized thereby.

A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

Embodiments of the present disclosure relate generally to single molecule arrays. More particularly, the present disclosure provides materials and methods for generating single molecule arrays using bottom-up self-assembly processes. Materials and methods of the present disclosure can be used to generate single molecule arrays with nanoapertures (e.g., zero mode waveguides) and for carrying out rapid, point-of-care biomolecule detection and quantification.

A patterned flow cell includes a substrate (100, 200) having a patterned array of metal oxide nano-patches (104, 202). Each of the metal oxide nano-patches (104, 202) has an organophosphate coating layer (106, 206) to increase the ability of the metal oxide (104, 204) to bind with DNA, proteins, or polynucleotides. A silane coating layer (108, 208) is deposited in the interstitial spaces on the substrate (100, 200) between the metal oxide nano-patches (104, 202) to prevent the binding of polynucleotides, DNA, or proteins in the interstitial spaces.

A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

Disclosed herein are methods for forming one or more nanoparticles. The methods include depositing a solution comprising a block copolymer and a metal salt into one or more square pyramidal nanoholes formed in a substrate, and annealing the substrate to provide a single nanoparticle in each of the one or more square pyramidal nanoholes.

Polymers synthesized by solid-phase synthesis are selectively released from a solid support by reversing the bias of spatially addressable electrodes. Change in the current and voltage direction at one or more of the spatially addressable electrodes changes the ionic environment which triggers cleavage of linkers that leads to release of the attached polymers. The spatially addressable electrodes may be implemented as CMOS inverters embedded in an integrated circuit (IC). The IC may contain an array of many thousands of spatially addressable electrodes. Control circuity may independently reverse the bias on any of the individual electrodes in the array. This provides fine-grained control of which polymers are released from the solid support. Examples of polymers that may be synthesized on this type of array include oligonucleotides and peptides.

Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.

De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.

The present disclosure provides methods of patterning cells on a surface of a substrate. The methods include disposing a pattern of nucleic acids on a surface of a substrate, and contacting the patterned nucleic acids under hybridization conditions with a first suspension of cells, where cells of the first suspension include cell surface-attached nucleic acids complementary to the patterned nucleic acids, and where the cell surface-attached nucleic acids hybridize to the patterned nucleic acids to pattern the cells on the surface of the substrate. Systems and kits for practicing the methods are also provided.