Provided herein are methods for de-crosslinking fixed biological samples (e.g., fixed biological samples including aminal crosslinks). The compositions and methods disclosed can de-crosslink oligonucleotides (e.g., DNA or RNA) or proteins from fixed biological samples (e.g., fixed biological samples with aminal crosslinks), wherein the de-crosslinked biological sample is compatible with and can be used in spatial gene expression analysis.

Provided herein is a method for detecting the presence of a COVID-19 virus RNA or other pathogenic respiratory viruses, such as an influenza virus, or other RNA of interest in a sample. Nucleic acids are obtained from the sample and are used as a template in a combined isothermal reverse transcription, RNAse H and isothermal amplification reaction to generate single stranded RNA amplicons containing sequences complementary to fluorescent labeled detector probes. The single-stranded RNA amplicons hybridize to the detector probe and to hybridization probes with sequences complementary to a sequence determinant in the COVID-19 or other virus RNAs. The microarray is imaged to detect fluorescent signals thereby identifying the virus.

Provided herein is a method for detecting the presence of a COVID-19 virus RNA or other pathogenic respiratory viruses, such as an influenza virus, or other RNA of interest in a sample. Nucleic acids are obtained from the sample and are used as a template in a combined isothermal reverse transcription, RNAse H and isothermal amplification reaction to generate single stranded RNA amplicons containing sequences complementary to fluorescent labeled detector probes. The single-stranded RNA amplicons hybridize to the detector probe and to hybridization probes with sequences complementary to a sequence determinant in the COVID-19 or other virus RNAs. The microarray is imaged to detect fluorescent signals thereby identifying the virus.

An apparatus includes a substrate, a first heating element, and a second heating element. The substrate includes a first portion, a second portion, and a third portion that is between the first portion and the second portion. The first portion is characterized by a first thermal conductivity, the second portion is characterized by a second thermal conductivity, and the third portion is characterized by a third thermal conductivity. The third thermal conductivity is less than the first thermal conductivity and the second thermal conductivity. The first heating element is coupled to the first portion of the substrate, and is configured to produce a first thermal output. The second heating element is coupled to the second portion of the substrate, and configured to produce a second thermal output. The second thermal output is different from the first thermal output.

An apparatus includes a substrate, a first heating element, and a second heating element. The substrate includes a first portion, a second portion, and a third portion that is between the first portion and the second portion. The first portion is characterized by a first thermal conductivity, the second portion is characterized by a second thermal conductivity, and the third portion is characterized by a third thermal conductivity. The third thermal conductivity is less than the first thermal conductivity and the second thermal conductivity. The first heating element is coupled to the first portion of the substrate, and is configured to produce a first thermal output. The second heating element is coupled to the second portion of the substrate, and configured to produce a second thermal output. The second thermal output is different from the first thermal output.

Provided are methods and kits for detecting and quantifying a sequence difference relative to a target polynucleotide sequence, and methods for developing assays. Target polynucleotide sequences are examined to determine if any of the sequences vary by at least one nucleotide difference. Promiscuous probes that have on and off-target binding at different binding efficiencies at permissive temperature are used, so that differences in polynucleotide sequences are reliably detected and quantified in a single well with fewer types of labeled probes, including by polymerase chain reaction of any of a range of sequences where there is interest in detecting an at least one nucleotide difference relative. The target sequences may be a reference polynucleotide sequence indicative of a first state, such as “normal” and another sequence that varies by at least one polynucleotide indicative of a different second state, such as a mutation, disease condition, or predisposition thereto.

Provided are methods and kits for detecting and quantifying a sequence difference relative to a target polynucleotide sequence, and methods for developing assays. Target polynucleotide sequences are examined to determine if any of the sequences vary by at least one nucleotide difference. Promiscuous probes that have on and off-target binding at different binding efficiencies at permissive temperature are used, so that differences in polynucleotide sequences are reliably detected and quantified in a single well with fewer types of labeled probes, including by polymerase chain reaction of any of a range of sequences where there is interest in detecting an at least one nucleotide difference relative. The target sequences may be a reference polynucleotide sequence indicative of a first state, such as “normal” and another sequence that varies by at least one polynucleotide indicative of a different second state, such as a mutation, disease condition, or predisposition thereto.

Provided is a diagnostic kit for determining infection with Methicillin-Resistant Staphylococcus aureus (MRSA) in a specimen, and a method for determining the infection with MRSA using the diagnostic kit is performed by visually observing a color change after LAMP reaction, and the color change is caused by a change in a magnesium concentration and confirmed using a specific dye compound which sensitively reacts with magnesium ions. The amplification of the MRSA DNA is performed using the loop-mediated isothermal amplification (LAMP), so that the diagnostic kit has advantages of being conveniently used anytime and anywhere and quickly diagnosing.

The present invention discloses a naïve antibody phage display library (APDL), a process for producing the same and a method of obtaining manufacturable antibodies as soluble Fabs from the antibody phage display library.

The present invention provides a system and method for automatic nucleic acid extraction and qualitative analysis. The system comprises a magnetic rotary mixer which comprises a plurality of magnetic rods for generating magnetism, configured to be retractable from the magnetic rotary mixer; a plurality of spin shaft for mounting tips, and the plurality of magnetic rods extend therein; an auto stage comprises a plate holder, which allows a plate place thereon; a mixer holder to hold the magnetic rotary mixer over the plate holder; and a heat plate, disposed under the plate holder for heating the plate. The present invention provides an automated high-throughput nucleic acid extraction and qualitative diagnosis with high efficiency and high accuracy, which is easy to interpret for operators, and realize that nucleic acid extraction and molecular detection can be completed at one time in a single device.