In an example of a method for making a flow cell, a metal material is sputtered over a transparent substrate including depressions separated by interstitial regions to form a metal film having a first thickness over the interstitial regions and having a second thickness over the depressions, the second thickness being about 30 nm or less and being at least ⅓ times smaller than the first thickness. A light sensitive material is deposited over the metal film; and the metal film is used to develop the light sensitive material through the transparent substrate to define an altered light sensitive material at a first predetermined region over the transparent substrate. The altered light sensitive material is utilized to generate a functionalized layer at the first predetermined region or at a second predetermined region over the transparent substrate.

Fluorophores are used during the synthesis of oligonucleotides to achieve real-time quality control of the synthesis process. Fluorescence may indicate successful addition of individual nucleotides to a growing oligonucleotide strand or removal of a blocking group. The oligonucleotides may be created by enzymatic synthesis using terminal deoxynucleotidyl transferase (TdT). The synthesis is performed on an addressable array so that oligonucleotides with different sequences are created in parallel on different regions of the array. The oligonucleotide sequences are predetermined and the locations of synthesis on the array are controlled. Observed fluorescence is compared to expected locations of fluorescence as determined by the oligonucleotide sequences and the arrangement on the array. Thus, the fidelity of oligonucleotide synthesis is checked as synthesis proceeds. If a variation is found, a mitigating action is taken such as repeating addition of a species of nucleotide or repeating a deblocking step.

Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

A nano-structured ceramic film with controlled pore size for the high throughput synthesis of oligonucleotides (DNA and RNA). The film can be cut into chips of predetermined size, and code printed for optical recognition in automated DNA synthesizers. The chips are easily activated under very mild conditions and silanization proceeds uniformly to allow reagents to flow unhindered through its open pores. Mono layer modifications, such as covalently bound silane coupling agents, allows for the addition of universal linkers and improved yields compared to conventional approaches.

A high-throughput hybridization and reading method for biochips uses probes with different marks to specifically connect single nucleotide loci by conducting connection between the probes and target genes at different temperatures, and performing hybridization at the same temperature after the probes are connected, thereby achieving hybridization detection for various loci in a single chip. The method enables fast detection for multiple loci as required by personalized medicine. The detection is high-throughput and systematized and provides highly visualized and highly accurate results. The method allows detection for different loci at different hybridization temperatures to be done simultaneously. The method features highly uniform and repeatable detection, making biochips more efficient and utility in terms of detection. Besides, the chip is easy to prepare and use, thus having a good promotional value.

Nucleic acid memory strands encoding digital data using a sequence of homopolymer tracts of repeated nucleotides provides a cheaper and faster alternative to conventional digital DNA storage techniques. The use of homopolymer tracts allows for lower fidelity, high throughput sequencing techniques such as nanopore sequencing to read data encoded in the memory strands. Specialized synthesis techniques allow for synthesis of long memory strands capable of encoding large volumes of data despite the reduced data density afforded by homopolymer tracts as compared to conventional single nucleotide sequences.

A data storage medium is disclosed comprising a two-dimensional (2D) support structure onto which artificially synthesized DNA molecules encoding digital information are placed and then covered with a protective layer. The 2D support structure is formed from a material such as metal foil, glass, or plastic. The 2D support structure may be functionalized with positively charged molecules to improve DNA adhesion. The DNA is protected from degradation by encapsulation in a protective layer of a non-reactive material such as silica or a thin layer of metal. A process for storing DNA on 2D support structures is also disclosed. Correlation of specific DNA molecules with a physical storage location on a 2D support structure provides geometric addressability for selective access to specific digital information.

Disclosed herein is a substrate which includes a functional group protected with a photolabile group covalently attached to the substrate and a film of solvent thereof covering the substrate, where the thickness of the film is less than about 100 μm. Also disclosed herein are methods of preparing such substrates. Further disclosed are methods of synthesizing polymers, methods of synthesizing arrays of polymers and methods of removing photolabile protecting groups. These methods all employ covering the substrate with a thin film of solvent where the thickness of the film is less than 100 μm.

Provided herein is technology relating to microarrays and particularly, but not exclusively, to microarray devices and systems, methods for producing microarrays, and methods of using microarrays.

Provided herein is a method for manufacturing a microarray system, for example, 3-dimensional lattice microarray system, for DNA sequence detection and analysis. A solid support, such as a plastic substrate, is contacted with a formulation containing a plurality of nucleic acid probes, a plurality of bifunctional polymer linkers, such as oligothymidine linkers, and a solvent mixture of water and a water-miscible liquid. The bifunctional polymer linkers are attached to the solid support and the water is evaporated. Then the nucleic acid probes are attached to the bifunctional polymer linker.