A device and method for the rapid on-site detection of inhibitors of enzymes, such as acetylcholinesterase, is described wherein the device contains all reagents added to a sample pad containing dried releasable enzyme creating a reaction mixture wherein inhibitor deactivates the enzyme, while said reaction mixture travels via a longitudinal membrane to a distal porous pad containing a substrate for the enzyme. The reaction of the enzyme and the substrate results in a product that can generate a measurable signal such as color, fluorescence or luminescence to serve as a reporter. Signal that is generated at this reaction zone is inversely proportional to inhibitor concentration in the test sample. A device containing two such strips, one for a test sample, the other for a negative control fluid as an onboard comparator is described. A purpose-built reader or an illuminating device, such as, containing an incandescent light source, a diode, a UV light source or any other illumination source that is suitable for the reporter or mere visualization is used to determine the level of reporter.

A device and method for the rapid on-site detection of inhibitors of enzymes, such as acetylcholinesterase, is described wherein the device contains all reagents added to a sample pad containing dried releasable enzyme creating a reaction mixture wherein inhibitor deactivates the enzyme, while said reaction mixture travels via a longitudinal membrane to a distal porous pad containing a substrate for the enzyme. The reaction of the enzyme and the substrate results in a product that can generate a measurable signal such as color, fluorescence or luminescence to serve as a reporter. Signal that is generated at this reaction zone is inversely proportional to inhibitor concentration in the test sample. A device containing two such strips, one for a test sample, the other for a negative control fluid as an onboard comparator is described. A purpose-built reader or an illuminating device, such as, containing an incandescent light source, a diode, a UV light source or any other illumination source that is suitable for the reporter or mere visualization is used to determine the level of reporter.

Provided herein is a reaction mixture comprising Cas9 and a non-ionic surfactant, e.g., a polyoxyethylene surfactant. In certain embodiments, the reaction mixture may comprise a Cas9 protein, a guide RNA, a salt, a buffering agent, a nucleic acid target and a non-ionic surfactant. Kits are also provided. In certain embodiments, a kit may comprise: a Cas9 protein; and a concentrated reaction buffer comprising salt, a buffering agent and a non-ionic surfactant.

Provided herein is a reaction mixture comprising Cas9 and a non-ionic surfactant, e.g., a polyoxyethylene surfactant. In certain embodiments, the reaction mixture may comprise a Cas9 protein, a guide RNA, a salt, a buffering agent, a nucleic acid target and a non-ionic surfactant. Kits are also provided. In certain embodiments, a kit may comprise: a Cas9 protein; and a concentrated reaction buffer comprising salt, a buffering agent and a non-ionic surfactant.

A reagent kit used for detecting lipoprotein-associated phospholipase A2, and a preparation method for the reagent kit. The reagent kit comprises one or a plurality of first anti-lipoprotein-associated phospholipase A2 antibodies used for binding lipoprotein-associated phospholipase A2 to be measured, and one or a plurality of second anti-lipoprotein-associated phospholipase A2 antibodies marked with a trace marker and binding with the lipoprotein-associated phospholipase A2 to be measured at another site, different from the binding site of the lipoprotein-associated phospholipase A2 to be measured and the first anti-lipoprotein-associated phospholipase A2 antibodies. The reagent kit also comprises a displacing agent, so as to further increase the detection accuracy of the reagent kit. A method using the reagent kit for the detection of lipoprotein-associated phospholipase A2 may take serum as a detection sample, has high repeatability and high accuracy, and measures the concentration of lipoprotein-associated phospholipase A2 in the sample in a highly sensitive manner.

The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of α-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.

The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of α-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.

A method of detecting a virus having a hemagglutinin-esterase activity in a sample is disclosed, the method includes: contacting the sample with a substrate for an enzyme of hemagglutinin-esterase (HE) of coronavirus or hemagglutinin-esterase fusion protein (HEF) of influenza C virus; and detecting activity of the enzyme, the detection of the activity indicates that the sample contains coronavirus or influenza C virus.

Provided is a compound comprising the structure:

(SIG)-(SI-MOD).sub.m.

In this compound, SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. With this compound, when MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided is a method of determining whether a sample comprises an activator, using the above-described compound. Additionally provided is a method of determining whether a cell comprises a nitroreductase using the above-described compound where nitroreductase is the activator. Further provided is a method of determining whether a mammalian cell is hypoxic using the above-described compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase, using the above-described compound where nitroreductase is the activator, is also provided. Also provided is a method of identifying nitroreductase in a sample, using the above-described compound where nitroreductase is the activator.

Provided is a compound comprising the structure:

(SIG)-(SI-MOD).sub.m.

In this compound, SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. With this compound, when MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided is a method of determining whether a sample comprises an activator, using the above-described compound. Additionally provided is a method of determining whether a cell comprises a nitroreductase using the above-described compound where nitroreductase is the activator. Further provided is a method of determining whether a mammalian cell is hypoxic using the above-described compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase, using the above-described compound where nitroreductase is the activator, is also provided. Also provided is a method of identifying nitroreductase in a sample, using the above-described compound where nitroreductase is the activator.