The present disclosure relates to nanolithographical cell patterning. In some aspects, the present disclosure provides materials and methods for making an oriented array.

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.

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.

Methods and apparatus for manufacturing a microfluidic arrangement are disclosed. In one arrangement, a continuous body of a first liquid is provided in direct contact with a first substrate. A second liquid covers the first liquid. A separation fluid, immiscible with the first liquid, is propelled through at least the first liquid and into contact with the first substrate along all of a selected path on the surface of the first substrate. First liquid that was initially in contact with all of the selected path is displaced away from the selected path. The first liquid is divided to form sub-bodies of first liquid that are separated from each other. For each of one or more of the sub-bodies, a sub-body footprint represents an area of contact between the sub-body and the first substrate, and all of a boundary of the sub-body footprint is in contact with a closed loop of the selected path surrounding the sub-body footprint.

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.

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.

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.

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.

Methods and apparatus for manufacturing a microfluidic arrangement are disclosed. In one arrangement, a continuous body of a first liquid is provided in direct contact with a first substrate. A second liquid covers the first liquid. A separation fluid, immiscible with the first liquid, is propelled through at least the first liquid and into contact with the first substrate along all of a selected path on the surface of the first substrate. First liquid that was initially in contact with all of the selected path is displaced away from the selected path. The first liquid is divided to form sub-bodies of first liquid that are separated from each other. For each of one or more of the sub-bodies, a sub-body footprint represents an area of contact between the sub-body and the first substrate, and all of a boundary of the sub-body footprint is in contact with a closed loop of the selected path surrounding the sub-body footprint.

An example of a flow cell includes a substrate and a reaction area defined in or over the substrate. The reaction area includes two angularly offset and non-perpendicular surfaces relative to a planar surface of the substrate, a polymeric hydrogel positioned over at least a portion of each of the two angularly offset and non-perpendicular surfaces; a first primer set attached to the polymeric hydrogel that is positioned over the portion of a first of the two angularly offset and non-perpendicular surfaces; and a second primer set attached to the polymeric hydrogel that is positioned over the portion of a second of the two angularly offset and non-perpendicular surfaces, wherein the first and second primer sets are orthogonal.