Abstract: In some embodiments, techniques are provided for conducting similarity-based searches using DNA. In some embodiments, sets of features that represent stored data sets are encoded in DNA sequences such that a hybridization yield between a molecule having a given stored DNA sequence and a molecule having a reverse complement of a DNA sequence that encodes a set of features that represent a query data set reflects an amount of similarity between the set of features that represent the query data set and the set of features encoded in the given stored DNA sequence. In some embodiments, machine learning techniques are used to determine the DNA sequence encoding. In some embodiments, machine learning techniques are used to predict hybridization yields between DNA molecules.

Abstract: High surface area coatings are applied to solid substrates to increase the surface area available for solid-phase synthesis of polymers. The high surface area coatings use three-dimensional space to provide more area for functional groups to bind polymers than an untreated solid substrate. The polymers may be oligonucleotides, polypeptides, or another type of polymer. The solid substrate is a rigid supportive layer made from a material such as glass, a silicon material, a metal material, and plastic. The coating may be thin films, hydrogels, microparticles. The coating may be made from a metal oxide, a high-? dielectric, a low-? dielectric, an etched metal, a carbon material, or an organic polymer. The functional groups may be hydroxyl groups, amine groups, thiolate groups, alkenes, n-alkenes, alkalines, N-Hydroxysuccinimide (NHS)-activated esters, polyaniline, aminosilane groups, silanized oxides, oligothiophenes, and diazonium compounds.

Abstract: Polynucleotides such as DNA are stored inside vesicles formed from self-assembling membranes. The vesicles may be protocells, liposomes, micelles, colloidosomes, proteinosomes, or coacervates. The vesicles may include surface functionalization to improve polynucleotide encapsulation and/or to bind polynucleotides having specific sequences. Encapsulation in vesicles provides protection for the polynucleotides. Additional protection is provided by addition of one or more stabilizers. The stabilizer may be nucleic-acid stabilizers that stabilize the polynucleotides or may be a protective structural layer around the vesicles such as a layer of silica. A process for stably storing polynucleotides in vesicles and a process for recovering stored polynucleotides from vesicles are both disclosed. The polynucleotides may be used for storage of digital information.

Abstract: A method for DNA synthesis using protected nucleosides is disclosed. The nucleosides may be nucleoside triphosphates or nucleoside phosphoramidites with nucleobases attached to electrochemically-cleavable linkers. Removal of a protecting group by application of a voltage in solution triggers a cyclization reaction that cleaves the electrochemically-cleavable linkers. The electrochemically-cleavable linkers may include an amide linkage and an amide that forms a lactam or an ester linkage and a protected alcohol that forms a lactone when the protecting group is removed. The voltage used to cleave the electrochemically-cleavable linkers may be generated by activation of individual electrodes on a microelectrode array. The microelectrode array can be a substrate for solid-phase synthesis of oligonucleotides. Activation of specific electrodes removes the protecting groups at those electrodes and thus enables spatially-controlled extension of the oligonucleotides.

Abstract: Polynucleotides such as DNA are stored inside vesicles formed from self-assembling membranes. The vesicles may be protocells, liposomes, micelles, colloidosomes, proteinosomes, or coacervates. The vesicles may include surface functionalization to improve polynucleotide encapsulation and/or to bind polynucleotides having specific sequences. Encapsulation in vesicles provides protection for the polynucleotides. Additional protection is provided by addition of one or more stabilizers. The stabilizer may be nucleic-acid stabilizers that stabilize the polynucleotides or may be a protective structural layer around the vesicles such as a layer of silica. A process for stably storing polynucleotides in vesicles and a process for recovering stored polynucleotides from vesicles are both disclosed. The polynucleotides may be used for storage of digital information.

Abstract: A hardware acceleration component is provided for implementing a convolutional neural network. The hardware acceleration component includes an array of N rows and M columns of functional units, an array of N input data buffers configured to store input data, and an array of M weights data buffers configured to store weights data. Each of the N input data buffers is coupled to a corresponding one of the N rows of functional units. Each of the M weights data buffers is coupled to a corresponding one of the M columns of functional units. Each functional unit in a row is configured to receive a same set of input data. Each functional unit in a column is configured to receive a same set of weights data from the weights data buffer coupled to the row. Each of the functional units is configured to perform a convolution of the received input data and the received weights data, and the M columns of functional units are configured to provide M planes of output data.

Abstract: Reagents and solvents used for polymer synthesis are reused or recycled rather than discarded. The outflow from each step of polymer synthesis may be collected separately in one of multiple dedicated containers. Reuse returns the outflow from a step of polymer synthesis back to an input of a polymer synthesizer for subsequent use in that same step. Recycling processes the outflow from one or more steps of polymer synthesis to restore original concentrations or purity levels for use in a later synthesis run. Quality control analysis may determine if outflow collected from a polymer synthesizer is reused or recycled. These techniques reduce reagent cost and waste quantity. These techniques may be used with phosphoramidite or enzyme-based synthesis of deoxyribonucleic acid (DNA).

Abstract: De novo polynucleotide synthesis is performed with a substrate-bound polymerase. The polymerase is attached to a solid substrate such as a microelectrode array. The polymerase adds nucleotides to growing polynucleotides strands that are also attached to the solid substrate. Spatial control of polymerase activity is achieved by changing the rate of nucleotide polymerization at selected locations on the surface of the solid substrate. The rate of polymerization is changed by inhibiting or promoting activity of the polymerase. In some implementations, activation of electrodes in the microelectrode array changes the rate of nucleotide polymerization. Nucleotides are added to the growing polynucleotide strands at areas where the polymerase is active. By varying the locations where the substrate-bound polymerase is active and the species of nucleotide added, a population of polynucleotides with different, arbitrary sequences is synthesized on the surface of the solid substrate.

Abstract: A universal template strand built with universal base analogs is used as a template for polynucleotide synthesis. The universal template strand can hybridize to any sequence of nucleotides. A new polynucleotide is synthesized by using a polymerase to extend a primer hybridized to the universal template strand. Unlike primer extension in polymerase chain reactions, base pairing with nucleotides in the template strand does not specify the sequence of the new polynucleotide. Instead, the sequence of the new polynucleotide is specified by the order of addition of protected nucleotides. After addition of a single species of protected nucleotide, the blocking group is removed and another protected nucleotide is added. The order of nucleotide addition can be varied to create any sequence. After synthesis, the polynucleotide can be dehybridized from the universal template strand. The universal template strand may then be reused to synthesize a different polynucleotide.

Abstract: A data storage medium is disclosed comprising a substrate covered with alternating layers of a polycationic molecule and artificially synthesized DNA molecules encoding digital information. The magnetic substrate may be a metallic nanoparticle formed from a metal such as iron or cobalt. The polycationic molecule may be polyethyleneimine (PEI). The DNA is protected from degradation by encapsulation in silica. A process for stably storing DNA is also disclosed. Stored DNA may be freed from the silica for sequencing or other analysis by washing the silica-coated DNA with a buffered hydrogen fluoride solution. Storage densities of more than 7% DNA by weight are achieved on nanoparticles.

Abstract: This disclosure provides electrochemically-cleavable linkers with cleavage potentials that are less than the redox potential of the solvent in which the linkers are used. In some applications, the solvent may be water or an aqueous buffer solution. The linkers may be used to link a nucleotide to a bound group. The linkers include a cleavable group which may be one of a methoxybenzyl alcohol, an ester, a propargyl thioether, or a trichloroethyl ether. The linkers may be cleaved in solvent by generating an electrode potential that is less than the redox potential of the solvent. In some implementations, an electrode array may be used to generate localized electrode potentials which selectively cleave linkers bound to the activated electrode. Uses for the linkers include attachment of blocking groups to nucleotides in enzymatic oligonucleotide synthesis.

Abstract: This disclosure provides techniques and systems for efficient random access to digital data encoded in oligonucleotides (e.g., DNA). Random access to DNA-encoded data is provided by amplification using polymerase chain reaction (PCR) and primer pairs that selectively amplify only the oligonucleotides encoding a desired set of digital data. Multiple separate random-access requests are prepared for multiplex DNA sequencing by generating copy-normalized amplification products. Copy-normalized amplification products are efficiently created by performing multiple singleplex PCR reactions in parallel and measuring the quantity of oligonucleotides in each reaction. The PCR reactions are performed in parallel through the use of multiple isolated reaction volumes such as water-in-oil microdroplets or individual wells on a plate.

Abstract: A data storage medium is disclosed comprising a substrate covered with alternating layers of a polycationic molecule and artificially synthesized DNA molecules encoding digital information. The magnetic substrate may be a metallic nanoparticle formed from a metal such as iron or cobalt. The polycationic molecule may be polyethyleneimine (PEI). The DNA is protected from degradation by encapsulation in silica. A process for stably storing DNA is also disclosed. Stored DNA may be freed from the silica for sequencing or other analysis by washing the silica-coated DNA with a buffered hydrogen fluoride solution. Storage densities of more than 7% DNA by weight are achieved on nanoparticles.

Abstract: Electrically controlled hybridization is used to selectively assemble oligonucleotides on the surface of a microelectrode array. Controlled activation of individual electrodes in the microelectrode array attracts oligonucleotides in solution to specific regions of the array where they hybridize to other oligonucleotides anchored on the array. The oligonucleotides that hybridize may provide locations for subsequent oligonucleotides to hybridize. The active electrodes and the oligonucleotides in solution may be varied during each round of synthesis. This allows for multiple oligonucleotides each with different and specific sequences to be created in parallel. This is accomplished without the use of phosphoramidite chemical synthesis or template-independent DNA polymerase enzymatic synthesis. Oligonucleotides created with these techniques may be used to encode digital data. Fully assembled oligonucleotides may be separated from the array and sequenced, stored, or otherwise processed.

Abstract: High surface area coatings are applied to solid substrates to increase the surface area available for solid-phase synthesis of polymers. The high surface area coatings use three-dimensional space to provide more area for functional groups to bind polymers than an untreated solid substrate. The polymers may be oligonucleotides, polypeptides, or another type of polymer. The solid substrate is a rigid supportive layer made from a material such as glass, a silicon material, a metal material, and plastic. The coating may be thin films, hydrogels, microparticles. The coating may be made from a metal oxide, a high-? dielectric, a low-? dielectric, an etched metal, a carbon material, or an organic polymer. The functional groups may be hydroxyl groups, amine groups, thiolate groups, alkenes, n-alkenes, alkalines, N-Hydroxysuccinimide (NHS)-activated esters, polyaniline, aminosilane groups, silanized oxides, oligothiophenes, and diazonium compounds.

Abstract: Array-based enzymatic oligonucleotide synthesis creates a large number of polynucleotides using an uncontrolled and template independent polymerase such as terminal deoxynucleotidyl transferase (TdT). Spatial control of reaction conditions on the surface of the array allows creation of polynucleotides with a variety of arbitrary sequences. Spatial control may be implemented by removing protecting groups attached to nucleotides only at a selected location on the array or by other techniques such as location-specific regulation of enzymatic activity. The ratio of polynucleotides with protecting groups to unprotected polynucleotides used during a cycle of synthesis is adjusted to control the length of homopolymers created by the polymerase. Digital information may be encoded in the enzymatically synthesized polynucleotides.

Abstract: Redundancy information can be included in nucleotide symbol strings encoding underlying data. To avoid propagation of errors during the decoding process, during encoding, a constrained encoding can be performed before the redundancy information is computed. The redundancy information can be an outer encoding across multiple nucleotide symbol strings. An inner coding within nucleotide symbol strings can also be supported. Such redundancy information can be interleaved into the underlying nucleotide symbol strings to which the constrained encoding has been applied, resulting in a relaxed constraint. Insertion/deletion redundancy information can also be included in the resulting strings, and an insertion/deletion-sensitive sequence can be included to assist in recovering accurate sequences during decoding operations.

Abstract: Artificial polynucleotides may have different characteristics than natural polynucleotides so conventional base-calling algorithms may make incorrect base calls. However, because artificial polynucleotides are typically designed to have certain characteristics, the known characteristics of the artificial polynucleotide can be used to modify the base-calling algorithm. This disclosure describes polynucleotide sequencers adapted to sequence artificial polynucleotides by modifying a base-calling algorithm of the polynucleotide sequencer according to known characteristics of the artificial polynucleotides. The base-calling algorithm analyzes raw data generated by a polynucleotide sequencer and identifies which nucleotide base occupies a given position on a polynucleotide strand.

Abstract: Multiplex similarity search can be performed in a DNA data storage context. The described technologies can support a plurality of different DNA data storage queries in a single query run. A linking strand can be used to connect a query to its matching data element. After the query finds a matching data element, a result strand can be sequenced to the reveal the matching data element as well as which of the queries resulted in the match. Thus, in a multiplex similarity search scenario, a plurality of result strands from a single query run can be correlated to a plurality of different queries. Also, the result strand can be of significantly longer length than both the unmatched data strands and the unmatched query strands. Therefore, filtering based on length can provide more accurate results.

Abstract: A technique for clustering DNA reads from polynucleotide sequencing is described. DNA reads with a level of difference that is likely caused by errors in sequencing are grouped together in the same cluster. DNA reads that represent reads of different DNA molecules are placed in different clusters. The clusters are based on edit distance, which is the number of changes necessary to convert a given DNA read into another. The process of forming clusters may be performed iteratively and may use other types of distance that serve as an approximation for edit distance. Well clustered DNA reads provide a starting point for further analysis.