325results about How to "Low background" patented technology

SNAIL provides cost-efficient detection of specific nucleic acids in single cells, and may be combined with flow cytometry to simultaneously analyze large numbers of cells for a plurality of nucleic acids, e.g. at least one, to up to 5, up to 10, up to 15, up to 20 or more transcripts can be simultaneously analyzed, at a rate of up to about 50, 100, 250, 500 or more cells / second. The methods require only two primers for amplification, and may further include a detection primer.

The present invention relates to the use of fluorescently labeled nucleic acid probes to identify and image analytes in a biological sample. In the preferred embodiments, a probe is provided that comprises a target region able to specifically bind an analyte of interest and an initiator region that is able to initiate polymerization of nucleic acid monomers. After contacting a sample with the probe, labeled monomers are provided that form a tethered polymer. Triggered probes and self-quenching monomers can be used to provide active background suppression.

A nonlinear optical technique, such as second or third harmonic or sum or difference frequency generation, is used to detect binding interactions, or the degree or extent of binding, that comprise a conformational change. In one aspect of the present invention, the nonlinear optical technique detects a conformational change in a probe due to target binding. In another aspect of the invention, the nonlinear optical technique screens candidate probes by detecting a conformational change due to a probe-target interaction. In another aspect of the invention, the nonlinear optical technique screens candidate modulators of a probe-target interaction by detecting a conformational change in the presence of the modulator.

A method to detect the presence or amount of at least one molecule in a sample which employs a derivative of luciferin or a derivative of a fluorophore is provided.

Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in diagnosis.

Methods are provided for detecting formation of oligomeric complexes of molecules on the surface of cell membranes. These methods employ pairs of tagged probes and cleaving probes, each of which binds specificly to a cell surface molecule. The tagged probe includes a molecular tag that is linked to a first binding compound through a cleavable linkage, and the cleaving probe includes a second binding agent and a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to cell surface molecules that have formed an oligomeric complex results in release of the molecular tag from the binding compound, providing a measure of formation of the complex.

A nonlinear optical technique, such as second or third harmonic or sum or difference frequency generation, is used to detect binding interactions, or the degree or extent of binding, that comprise a conformational change. In one aspect of the present invention, the nonlinear optical technique detects a conformational change in a probe due to target binding. In another aspect of the invention, the nonlinear optical technique screens candidate probes by detecting a conformational change due to a probe-target interaction. In another aspect of the invention, the nonlinear optical technique screens candidate modulators of a probe-target interaction by detecting a conformational change in the presence of the modulator.

Disclosed is a method for in situ detection of one or more target nucleic acids based on a combination of an in situ hybridization (ISH) assay method and a general ISH signal amplification method. This new method produces high signal intensity and while keeps low background noise of signal amplification. The result can be consistently reproduced and the method can be easily adopted for routine clinic diagnostic use. Further, the invention relates to a kit, comprising the components of the ISH assay and a general ISH signal amplification assay, for sensitive detection of one or more target nucleic acids.

The subject invention relates to a new alarm which is based on using a quarternary tunable Mid-IR laser to measure both particles and gas at the same time. The measurement is done within an area of which the gas of interest will absorb the Mid-IR radiation. By widely tuning the emission wavelength of the laser, several wavelengths can be measured in order to accurately find both gas composition and particle density with one laser based sensor. We tested a new device which use radiation between 2.27 μm and 2.316 μm. Methane gas reduces intensity of the radiation at certain wavelengths in this device, while particles / fog reduce intensity for all wavelengths. In this case, fog should not trigger an alarm, while methane leaks should. This can also be applied for CO and smoke in which one sensor will measure both parameters to sound an alarm instead of just one parameter.

Disclosed is a method for in situ detection of one or more target nucleic acids based on a combination of RNAscope® method and a general ISH signal amplification method. This new method produces high signal intensity and while keeps low background noise of signal amplification. The result can be consistently reproduced and the method can be easily adopted for routine clinic diagnostic use. Further, the invention relates to a kit, comprising the components of RNAscope® assay and a general ISH signal amplification assay, for sensitive detection of one or more target nucleic acids.

Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.

New sensors, pixel detectors and different embodiments of multi-channel integrated circuit are disclosed. The new high energy and spatial resolution sensors use solid state detectors. Each channel or pixel of the readout chip employs low noise preamplifier at its input followed by other circuitry. The different embodiments of the sensors, detectors and the integrated circuit are designed to produce high energy and / or spatial resolution two-dimensional and three-dimensional imaging for different applications. Some of these applications may require fast data acquisition, some others may need ultra high energy resolution, and a separate portion may require very high contrast. The embodiments described herein addresses these issues and also other issues that may be useful in two and three dimensional medical and industrial imaging. The applications of the new sensors, detectors and integrated circuits addresses a broad range of applications such as medical and industrial imaging, NDE and NDI, security, baggage scanning, astrophysics, nuclear physics and medicine.

PCT No. PCT / CA95 / 00483 Sec. 371 Date Jun. 2, 1997 Sec. 102(e) Date Jun. 2, 1997 PCT Filed Aug. 15, 1995 PCT Pub. No. WO96 / 05292 PCT Pub. Date Feb. 22, 1996The present invention is concerned with the ability to differentiate between infection by HIV and immunization with an immunogenic preparation. Accordingly, the present invention provides a non-infectious, non-replicating, HIV retrovirus-like particle containing a heterologous antigenic marker, comprising an assembly of (a) an env gene product; (b) a pol gene product; (c) a gag gene product; and, (d) at least one non-retroviral, non-mammalian antigenic marker. The antigenic marker may have between 10 and 75 amino acid residues. In one embodiment, the amino acid sequence contains a tobacco mosaic virus (TMV) epitope obtained from the coat protein. In another embodiment, the marker is inserted into the gag gene product at an antigenically-active insertion site. The presence of the antigenic marker enables recognition that antiserum containing anti-HIV antibodies has been generated by exposure to the non-infectious retrovirus-like particles, as opposed to wild-type HIV infection, by testing for antibodies specific to the antigenic marker.

A rapid-sampling stochastic scanning multiphoton multifocal microscopy (SS-MMM) fluorescence imaging technique enables multiparticle tracking at rates upwards of 1,000 times greater than conventional single point raster scanning. Stochastic scanning of a diffractive optical element may generate a 10×10 hexagonal array of foci with a white noise driven galvanometer to yield a scan pattern that is random yet space-filling. SS-MMM may create a more uniformly sampled image with fewer spatio-temporal artifacts than obtained by conventional or multibeam raster scanning.

Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

A convenient handheld locator is provided for locating an item in an urban environment in which the locator is programmed to search for and locate specific items, with the detected item being displayed on the locator as to its identity or name, also displaying where the item is relative to the locator, as to position and range.

A method is provided for detecting biomarkers in rare circulating cells by forming an enriched population of cells immunomagnetically followed by biomarker detection using binding compounds having releasable molecular tags. Preferably, biomarkers comprising one or more protein-protein complexes are detected in circulating cancer cells metastasized from a solid tumor. In the presence of biomarkers, the molecular tags of the binding compounds are released and separated from the assay mixture for detection and / or quantification.

New sensors, pixel detectors and different embodiments of multi-channel integrated circuit are disclosed. The new high energy and spatial resolution sensors use solid state detectors. Each channel or pixel of the readout chip employs low noise preamplifier at its input followed by other circuitry. The different embodiments of the sensors, detectors and the integrated circuit are designed to produce high energy and / or spatial resolution two-dimensional and three-dimensional imaging for different applications. Some of these applications may require fast data acquisition, some others may need ultra high energy resolution, and a separate portion may require very high contrast. The embodiments described herein addresses these issues and also other issues that may be useful in two and three dimensional medical and industrial imaging. The applications of the new sensors, detectors and integrated circuits addresses a broad range of applications such as medical and industrial imaging, NDE and NDI, security, baggage scanning, astrophysics, nuclear physics and medicine.

The present invention relates to the use of fluorescently labeled nucleic acid probes to identify and image analytes in a biological sample. In the preferred embodiments, a probe is provided that comprises a target region able to specifically bind an analyte of interest and an initiator region that is able to initiate polymerization of nucleic acid monomers. After contacting a sample with the probe, labeled monomers are provided that form a tethered polymer. Triggered probes and self-quenching monomers can be used to provide active background suppression.

Methods and diagnostic kits for determining whether a subject may develop a or for diagnosing a neurodegenerative disease. The method includes quantitating the amount of alpha-synuclein and total protein in a cerebrospinal fluid (CSF) sample obtained from the subject and calculating a ratio of alpha-synuclein to total protein content; comparing the ratio of alpha-synuclein to total protein content in the CSF sample with the alpha-synuclein to total protein content ratio in CSF samples obtained from healthy neurodegenerative disease-free subjects; and (c) determining from the comparison whether the subject has a likelihood to develop neurodegenerative disease or making a diagnosis of neurodegenerative disease in a subject. A difference in the ratio of alpha-synuclein to total protein content indicates that the subject has a likelihood to develop a neurodegenerative disease or has developed a neurodegenerative disease.

The present invention provides novel primers and methods for the detection of specific nucleic acid sequences. The primers and methods of the invention are useful in a wide variety of molecular biology applications and are particularly useful in allele specific PCR.

Methods and kits are disclosed for determining, either in a homogeneous or heterogeneous assay format, one or more target analytes in a sample using binding compositions coupled to molecular tags by cleavable linkages. Generally, an assay mixture is formed comprising a sample and a reagent comprising multiple such binding compositions under conditions that permit stable complexes to form between the binding compositions and analytes. In one aspect of the invention, the interaction between the binding compositions and their respective binding sites brings a cleavage-inducing moiety into close proximity to cleavable linkages or provides a recognizable substrate for a cleavage-inducing moiety. In this way, one or more molecular tags for each of the analytes are released from the complexes. Released molecular tags are chromatographically separated and the presence and / or amount of the target analytes are determined based on the analysis of the released and separated molecular tags.

The invention relates to a magnetic particle chemiluminescence double-layer micro-fluidic chip used for whole-blood sample detection. The micro-fluidic chip comprises a top plate (1) and a bottom plate (2). The top plate comprises a sample feeding port (4), a sample filling region (12), a marked ligand storage pool (5) and a sample mixing region (13). The bottom plate comprises a filtering region (6), a magnetic particle coating region (7), a cleaning region (14), a detecting region (8), a cleaning fluid storage pool (9), a luminous substrate liquid storage pool (10) and a liquid release channel (16).

The invention provides methods and kits for detecting and / or measuring receptor homodimers on a cell surface membrane. In one aspect, the methods employ pairs of probes comprising binding compounds and a cleaving probe, such that at least one binding compound binds specifically to the same epitope of a membrane-bound analyte as the cleaving probe. The binding compound includes one or more molecular tags attached through a cleavable linkage, and the cleaving probe includes a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to a homodimer of a cell surface molecules results in release of molecular tags from the binding compounds, providing a measure of formation of the homodimeric complex.

The invention relates to a magnetic particle direct chemiluminiscence microfluidic chip for whole blood sample testing. The chip is composed of a top adhesive tape (10), a chip substrate (1) and a bottom adhesive tape (13); the chip substrate comprises a filtering area (2), a coating area (3), a cleaning area (4), a testing area (5), a cleaning liquid storing pool (7), a luminescence substrate liquid storing pool (8) and a waste liquid pool (11), wherein the testing area is connected with the cleaning liquid storing pool and the luminescence substrate liquid storing pool through liquid releasing channels (9) respectively; the top adhesive tape comprises a sample feeding opening (11) and a cleaning liquid storing pool demising hole (12).

Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.

A method to detect the presence or amount of at least one molecule in a sample which employs a derivative of luciferin or a derivative of a fluorophore is provided. Compounds and compositions for carrying out the methods of the invention are also provided.

In the serum, PSP94 occurs as a free form or is associated with a carrier protein. PSP94 in its bound form has been quantified in the blood of prostate cancer patients and these measurements have shown utility as evaluation or prognosis of prostate cancer. Diagnostic assays, methods, and kits for detecting a free form of PSP94, and reagents such as antibodies able to bind to a free form of PSP94 are disclosed herein.