A structured substrate includes a substrate body having an active side. The substrate body includes reaction cavities that open along the active side and interstitial regions that separate the reaction cavities. The structured substrate includes an ensemble amplifier positioned within each of the reaction cavities. The ensemble amplifier includes a plurality of nanostructures configured to at least one of amplify electromagnetic energy that propagates into the corresponding reaction cavity or amplify electromagnetic energy that is generated within the corresponding reaction cavity.

The present disclosure provides, inter alia, bivalent nanobody molecules and methods for treating or ameliorating the effects of a disease, such as long QT syndrome, or cystic fibrosis, in a subject, using the bivalent nanobody molecules disclosed herein. Also provided are methods of identifying and preparing nanobody binders that target proteins of interest.

The technology relates in part to methods and compositions for analyzing nucleic acid. In some aspects, the technology relates to methods and compositions for preparing a nucleic acid library from single-stranded nucleic acid fragments.

The invention relates to methods of enriching for target nucleic acid molecules, More particularly, the methods of enriching for target nucleic acid molecules comprise binding target nucleic acid molecules in a sample with one or more first target endonucleases that are specific to a first locus of a target region of the target nucleic acid molecules, separating the target nucleic acid molecules from nontarget nucleic acid molecules in the sample, and binding the separated target nucleic acid molecules with one or more second target endonucleases that are specific to a second locus of the target region of the target nucleic acid molecules, and uses thereof.

Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.

The present invention provides modified single primer extension-based methods for generating an amplified library of fragments of a target gene or genome of interest from a sample of fragmented DNA, wherein the library is suitable for use in detecting, quantifying and/or sequencing the target gene or genome of interest. The present invention also provides compositions for use in such methods. In some embodiments the present invention provides methods and compositions specifically for detecting, quantifying and/or sequencing circulating tumor derived HPV DNA.

The present invention provides modified single primer extension-based methods for generating an amplified library of fragments of a target gene or genome of interest from a sample of fragmented DNA, wherein the library is suitable for use in detecting, quantifying and/or sequencing the target gene or genome of interest. The present invention also provides compositions for use in such methods. In some embodiments the present invention provides methods and compositions specifically for detecting, quantifying and/or sequencing circulating tumor derived HPV DNA.

High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduces sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are sequencing adapters comprising a nondegenerate or variable length molecular barcode and compositions comprising a plurality of sequencing adapters, which can be useful for sequencing nucleic acids. Further provided are methods of using the sequencing adapters, including methods of sequencing nucleic acids, methods of identifying an error in a nucleic acid sequence, and methods of determining the number of nucleic acid molecules in a library.

Methods of preparing a plurality of sample-barcoded anchor-domain-flanked gene specific deoxyribonucleic acid (DNA) fragments from a template nucleic acid, e.g., ribonucleic acid (RNA), sample are provided. Aspects of the methods include employing a set of gene specific primer pairs, wherein each pair of gene specific primers is made up of a forward primer and a reverse primer, at least one of which includes a sample barcode domain. The methods find use in a variety of different applications, including high-throughput sequencing, e.g., expression profiling, applications, including of small biological samples, e.g., single-cells.

The present inventions describes a Facile Accelerated Specific Therapeutic (FAST) pipeline to rapidly design, built and test peptide nucleic acid treatments against mammalian or microbial genes of interest. The invention may include a bioinformatics application for facile and accelerated high throughput design of peptide nucleic acids (PNAs) that act as inhibitors of expression of specific targeted genes by binding to their mRNA to block translation, or PNA activators that can activate expression of target genes by binding to the respective promoter regions and recruitment of transcriptional activators. The invention may further involve automated and high throughput parallel synthesis of a PNA inhibitor/activator library for generation of on-site therapeutic molecules, which may reduce storage requirements, and the development of efficient delivery of therapeutic PNAs to host cells to overcome challenges of transport, toxicity, and bioavailability. The invention may further involve the testing of designed and built PNAs in a high throughput manner in a relevant infection, or mammalian cell culture model. The proposed invention may allow identification of important gene targets, and quickly generate translatable therapies that can be tested under host conditions, and most importantly develop a countermeasure platform that can be deployed on-site in the future to generate therapies in short time scales.