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Diagnostic methods and devices

A technology of reservoirs and detectors, applied in the field of diagnosis and devices

Active Publication Date: 2018-11-09
巴斯克自治区总局 +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A 5-fold increase in particle size at a constant gold concentration resulted in a 3-order improvement in the detection limit

Method used

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  • Diagnostic methods and devices
  • Diagnostic methods and devices
  • Diagnostic methods and devices

Examples

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[0190]As used herein, "thermosensitive polymer" or "temperature responsive polymer" refers to a polymer or combination of polymers that exhibit a drastic and discontinuous change in their physical properties with temperature. Specifically, the temperature-sensitive polymer may be a polymer that exhibits a change in solubility in water or an aqueous solution with temperature. Specific examples include: poly(styrenesulfonate) (PSS), poly(diallyldimethylammonium chloride) (PDADMAC), poly(allylamine) (PAH), poly(N-isopropylpropylene amide), poly[2-(dimethylamino)ethyl methacrylate] (pDMAEMA), hydroxypropyl cellulose, poly(vinyl caprolactam) and polyvinyl methyl ether.

[0191] The following examples are provided and should not be construed as limiting the scope of the claims.

Embodiment 1

[0193] Example 1 - Development of blocking and detection probes for BRAF mutation detection.

[0194] Mutations in the BRAF gene are found in more than 45% of melanomas, of which as many as 80% are the single-base mutation T1799A(V600E). It is believed that detection of this BRAF mutation status is a reliable surrogate for tumor testing.

[0195] To detect BRAF mutation status, two probes were developed:

[0196] 1) A blocking probe, complementary to the antisense strand of the mutant DNA sequence of interest; after heat denaturation of double-stranded DNA (dsDNA), this probe preferentially binds to the antisense strand of the mutant DNA sequence.

[0197] The blocking probes are short and provided in excess such that binding kinetics greatly favor blocking probe: formation of the antisense strand rather than reannealing of the mutant sequence dsDNA. This results in enrichment of the sense strand of the mutant DNA sequence for subsequent detection by the device.

[0198] 2)...

Embodiment 2

[0201] EXAMPLE 2 - COMPUTER MODELING OF INDICATE DEVICE CHARACTERISTICS.

[0202] In order to optimize the functional characteristics of the device, the INDICATE device was simulated in silico using computational modeling.

[0203] First, the individual mathematical equations responsible for the individual components are defined, and then proceed using a genetic algorithm (GA) (Goldberg and Deb, 1991, Foundations of Genetic Algorithms In Foundations of Genetic Algorithms, G.J.E. Rawlins ed. Morgan Kaufmann, San Mateo, CA) combination. Said techniques are well established in optimizing the design of plasmonic devices (Sukharev and Seideman, Nano Lett, 2006, Vol. 6, No. 4, pp. 715-719).

[0204] Simulations were used to optimize the devices with respect to: 1) high sensitivity (ie, low false negative rate); 2) high signal-to-noise ratio; and 3) high amplification of the input signal. Analysis was performed using Matlab Numerical Calculation (MathWorks) and the multiphysics met...

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Abstract

The present invention provides a method for detecting the presence or absence of a target analyte in a test sample, comprising the steps: i) providing a plurality of detector nanoparticles comprisinga first detector nanoparticle functionalised with a first probe specific for a first region of a target analyte and a second detector nanoparticle functionalised with a second probe specific for a second region of said target analyte; and ii) contacting said detector nanoparticles with a test sample under conditions suitable for the binding of the specific probes to the target analyte, wherein target analyte-induced agglomeration of the detector nanoparticles permits the release of a detectable signal means from a signal reservoir. Also provided are related devices and systems for performing the method of the invention.

Description

field of invention [0001] The present invention relates to methods and devices using signal amplification steps based on nanoparticle technology for the detection of biological analytes such as disease biomarkers. Background of the invention [0002] The present invention is directed to methods and related products and kits for the detection of biological analytes such as disease biomarkers, such as genetic mutations or non-host genetic material. [0003] Cancer is the second most common cause of death in the EU, responsible for approximately 1.75 million deaths in 2012 alone, the same year an estimated 3.45 million EU citizens were diagnosed with the condition. The gold standard for cancer diagnosis is histological examination of tissue; however, the procedure is expensive, not risk-free for the patient, and requires consistent evaluation by an expert pathologist. As a result, considerable attention has been paid to the development of techniques to detect non-invasive biom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6823C12Q1/6827G01N33/542G01N33/543B01L3/00
CPCB01L3/502707C12Q2600/156C12Q1/6827B01L3/502761G01N33/542G01N33/54346C12Q1/6823C12Q2523/313C12Q2527/101C12Q2537/125C12Q2547/107C12Q2563/155C12Q2563/159C12Q2565/113C12Q2565/519B82Y30/00C12Q2527/107
Inventor C·H·劳里L·巴萨贝-德斯蒙特斯T·谢菲尔L·M·莉兹马桑W·J·帕拉克
Owner 巴斯克自治区总局