Methods for selecting a binding-element are provided. The method comprised of different steps. A first mixture is formed using at least one target molecule and a plurality of oligomers, followed by incubating the first mixture to form a second mixture comprising at least one target-bound oligomer and at least one target-unbound oligomer. Then a first accelerator is added to cleave the target-unbound oligomer and the target-bound oligomer is separated from the target molecule. This is followed by addition of a second accelerator for ligation, and a third accelerator for amplification followed by sequencing and post sequence analysis to select the binding-element.

Methods for selecting a binding-element are provided. The method comprised of different steps. A first mixture is formed using at least one target molecule and a plurality of oligomers, followed by incubating the first mixture to form a second mixture comprising at least one target-bound oligomer and at least one target-unbound oligomer. Then a first accelerator is added to cleave the target-unbound oligomer and the target-bound oligomer is separated from the target molecule. This is followed by addition of a second accelerator for ligation, and a third accelerator for amplification followed by sequencing and post sequence analysis to select the binding-element.

Provided herein are compositions and methods for electronically sequencing polynucleotides using partially double-stranded polymer bridges. The bridges may span the space between first and second electrodes. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may hybridize to a portion of the bridge that is not double-stranded. Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal through the bridge, the changes being responsive to the respective hybridizations between the non-double stranded portion of the bridge and the labels corresponding to those nucleotides.

Provided herein are compositions and methods for electronically sequencing polynucleotides using partially double-stranded polymer bridges. The bridges may span the space between first and second electrodes. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may hybridize to a portion of the bridge that is not double-stranded. Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal through the bridge, the changes being responsive to the respective hybridizations between the non-double stranded portion of the bridge and the labels corresponding to those nucleotides.

An analyte [25] in a matrix is sensed using a sensing device having a detection probe [21] conjugated to a mediator-receptor [22] that is not a binder for the analyte. The sensor device is provided with mediators [23] conjugated to analyte-receptors [24], where the mediators are selected to bind to the mediator-receptors, and where the analyte-receptors are selected to bind to the analyte. In some embodiments, the mediators are bound to the detection probe by a tether molecule, or tether molecule fragment, or tether domain. In other embodiments, the mediators are not bound to the detection probe. The presence of the analyte is detected by optically or electrically detecting changes of distance between the mediators and the mediator-receptor, indicative of association and/or dissociation events between mediators and mediator-receptor, the characteristics of which are affected by whether the analyte is bound to the analyte-receptor.

An analyte [25] in a matrix is sensed using a sensing device having a detection probe [21] conjugated to a mediator-receptor [22] that is not a binder for the analyte. The sensor device is provided with mediators [23] conjugated to analyte-receptors [24], where the mediators are selected to bind to the mediator-receptors, and where the analyte-receptors are selected to bind to the analyte. In some embodiments, the mediators are bound to the detection probe by a tether molecule, or tether molecule fragment, or tether domain. In other embodiments, the mediators are not bound to the detection probe. The presence of the analyte is detected by optically or electrically detecting changes of distance between the mediators and the mediator-receptor, indicative of association and/or dissociation events between mediators and mediator-receptor, the characteristics of which are affected by whether the analyte is bound to the analyte-receptor.

The invention provides methods of amplification from a single primer or a pair of forward and reverse primers of limited nucleotide composition. Limited nucleotide composition means that the primers are underrepresented in at least one nucleotide type. Such primers have much reduced capacity to prime from each other or to extend initiated by mispriming from other than at their intended primer binding sites in a target nucleic acid.

Disclosed are methods for isothermal nucleic acid amplification and detection.

Disclosed are methods for isothermal nucleic acid amplification and detection.

The present invention encompasses a diagnostic test and method to authenticate the veracity of a vaccine. The diagnostic test and method are especially useful in a specific and sensitive immunochromatographic assay, performable within about 15 minutes for the authentication, validation, and veracity of a vaccine, such as a COVID-19 vaccine, in a vial prior to administration to a human.