This disclosure relates to methods for spatial profiling of analytes present in a biological sample. Also provided are methods for using spatially barcoded arrays to detect a biological analyte in a cell comprising a small molecule.

Provided herein are systems, devices and methods for the rapid and accurate measurement of analytes by assay of binding events, by direct, digital measurement of individually resolved analyte/reporter binding events. The digital molecular assay systems, devices and methods disclosed herein are capable of particle-by-particle readout using optical reporter molecules that detect and report the binding of a single analyte molecule, and report each such binding in binary format. Such digital molecular assay systems, devices and methods are useful in a variety of applications, such as on mobile electronic devices for use in the field.

Provided herein are systems, devices and methods for the rapid and accurate measurement of analytes by assay of binding events, by direct, digital measurement of individually resolved analyte/reporter binding events. The digital molecular assay systems, devices and methods disclosed herein are capable of particle-by-particle readout using optical reporter molecules that detect and report the binding of a single analyte molecule, and report each such binding in binary format. Such digital molecular assay systems, devices and methods are useful in a variety of applications, such as on mobile electronic devices for use in the field.

The invention relates to a method for the duplication of nucleic acids by means of a polymerase chain reaction, in the case of which a cycle consisting of the steps of denaturing, annealing and elongation is repeatedly performed. In one embodiment, in at least one passage of the cycle, the quotient of the duration of effect t.sub.A and the reaction volume V.sub.r irradiated by the energy source is less than 1 seconds per microliter. In another embodiment, in at least one passage of the cycle, the ratio of the duration of effect (t.sub.A) and the duration of the PCR cycle (t.sub.c) is less than 20%. In certain embodiments, the yield (g) of nucleic acids at the end of at least one of the passages of the cycle is less than 80% of the nucleic acids present at the start of the passage.

The invention relates to a method for the duplication of nucleic acids by means of a polymerase chain reaction, in the case of which a cycle consisting of the steps of denaturing, annealing and elongation is repeatedly performed. In one embodiment, in at least one passage of the cycle, the quotient of the duration of effect t.sub.A and the reaction volume V.sub.r irradiated by the energy source is less than 1 seconds per microliter. In another embodiment, in at least one passage of the cycle, the ratio of the duration of effect (t.sub.A) and the duration of the PCR cycle (t.sub.c) is less than 20%. In certain embodiments, the yield (g) of nucleic acids at the end of at least one of the passages of the cycle is less than 80% of the nucleic acids present at the start of the passage.

A fluidic network for carrying out, in parallel, a plurality of analyses of biological samples is disclosed. The network has a flow cell array with a plurality of reaction chambers. The reaction chambers each have a first channel connection and a second channel connection. The first channel connections are connected to a first supply channel and the second channel connections are connected to a second supply channel. The first supply channel and the second channel connection are interconnected by a circulation line. At least one component is connected to the circulation line so that component test reagents can be introduced into the reaction chambers of the flow cell array.

A fluidic network for carrying out, in parallel, a plurality of analyses of biological samples is disclosed. The network has a flow cell array with a plurality of reaction chambers. The reaction chambers each have a first channel connection and a second channel connection. The first channel connections are connected to a first supply channel and the second channel connections are connected to a second supply channel. The first supply channel and the second channel connection are interconnected by a circulation line. At least one component is connected to the circulation line so that component test reagents can be introduced into the reaction chambers of the flow cell array.

The present application relates to methods of detecting a target nucleic acid molecule in a sample. The method includes providing a sample containing a target nucleic acid molecule and a capture oligonucleotide molecule. In one embodiment, the capture oligonucleotide molecule has (i) a length of 30-60 base pairs, (ii) a 4-8 base pair overhang on its 3′ end, (iii) a 5′ tail, (iv) a target-specific portion between the 3′ end and the 5′ tail, (v) a deoxy-adenosine diphosphate content of 40-50%, (vi) no deoxy thymidine phosphate in the 3′ end or the 5′ tail, and (vii) the 3′ end and the 5′ tail having an ATP content which is 40-50% of that of the capture oligonucleotide molecule. In another aspect of the method of detecting, certain reagents are coupled to a solid support. The present application also relates to compositions and kits useful in carrying out the methods of the present application.

The present application relates to methods of detecting a target nucleic acid molecule in a sample. The method includes providing a sample containing a target nucleic acid molecule and a capture oligonucleotide molecule. In one embodiment, the capture oligonucleotide molecule has (i) a length of 30-60 base pairs, (ii) a 4-8 base pair overhang on its 3′ end, (iii) a 5′ tail, (iv) a target-specific portion between the 3′ end and the 5′ tail, (v) a deoxy-adenosine diphosphate content of 40-50%, (vi) no deoxy thymidine phosphate in the 3′ end or the 5′ tail, and (vii) the 3′ end and the 5′ tail having an ATP content which is 40-50% of that of the capture oligonucleotide molecule. In another aspect of the method of detecting, certain reagents are coupled to a solid support. The present application also relates to compositions and kits useful in carrying out the methods of the present application.

The disclosed embodiments relate to nanotechnology and to nano-electronics and molecular electronic sensors. In an exemplary embodiment, a nano-sensor having a nanoparticle complex attached at each end to a respective nano-electrode. An exemplary nanoparticle complex includes a biomolecule coupled at each end to a metallic nanoparticle to form a dumbbell-shaped molecular bridge. A method to manufacture single molecule dumbbell nanowires for forming conductive molecular bridges includes the steps of: providing a double-stranded nucleic acid with terminal 3′ thiol modification on both the strands conjugated to a gold (Au) nanoparticle (AuNP) on each end; purifying single biomolecule dumbbells from aggregates using size-exclusion chromatography; imaging the eluted products by electron microscopy to validate formation of single molecule dumbbells; trapping a single molecule dumbbell between a pair of nanoelectrodes on a substrate, the electrodes separated by a nanogap; and measuring the conductivity of a trapped single molecule dumbbell.