PCR-Ready Composition for Mycobacterial Detection

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Solution Overview

Problem

Current diagnostic methods for tuberculosis, particularly in developing countries, face challenges due to the slow growth of mycobacteria, low organism levels in patients, and the need for complex laboratory conditions, leading to delayed and unreliable detection and identification of Mycobacterial pathogens.

Innovation Solution

Development of PCR-ready compositions containing a heat-stable polymerase, deoxynucleotide triphosphates, chelating agents, osmolarity agents, albumin, salts, and buffers, which can be used to detect nucleic acid sequences specific to Mycobacteria, allowing for rapid identification and quantitation at ambient temperatures without the need for cold chains or specialized equipment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional culture methods are used to diagnose Mycobacterial infections, then accurate identification of pathogens can be achieved, but the diagnosis process takes 3-7 days or longer due to slow growth of mycobacteria

Engineering Contradiction:
Improvepathogen identification accuracyVSAvoiddiagnosis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing nucleic acid extraction and PCR amplification before final detection. The composition prepares the sample in advance with all necessary reagents (polymerase, dNTPs, buffers, chelating agents) already mixed and stabilized, so that when detection is needed, the amplification can proceed immediately without waiting for culture growth or preparing reagents separately. This preliminary preparation of the detection system resolves the contradiction by enabling rapid results while maintaining accuracy.

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If complex laboratory conditions and equipment are used for Mycobacterial detection, then detection accuracy is improved, but the complexity of the detection system increases

Engineering Contradiction:
Improvedetection accuracyVSAvoidlaboratory equipment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into a single integrated composition that includes polymerase, dNTPs, buffers, chelating agents, and primers all in one stable mixture. This consolidation eliminates the need for separate preparation of multiple reagents and equipment steps, allowing the detection to be performed with minimal equipment while maintaining high accuracy through the optimized composition formulation.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The composition is designed to be self-service by containing all necessary components for PCR amplification in a pre-mixed, stable formulation that requires no additional preparation or complex equipment. The heat-stable polymerase and stabilized reagents enable the system to function autonomously once the sample is added, reducing dependence on complex laboratory infrastructure while maintaining detection accuracy.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If biological samples are collected and transported in resource-limited settings, then patient accessibility is improved, but maintaining nucleic acid integrity becomes difficult without cold chains

Engineering Contradiction:
Improvesample collection accessibilityVSAvoidnucleic acid stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by using a heat-stable polymerase and optimizing buffer conditions (pH, ionic strength, chelating agents) that maintain nucleic acid stability at ambient temperatures. The composition's physical and chemical parameters are specifically adjusted to prevent degradation without requiring refrigeration, enabling sample collection and transport in resource-limited settings while preserving nucleic acid integrity for accurate detection.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables safe collection, handling, and transport of biological samples, facilitating rapid and accurate detection of Mycobacterial pathogens, even in remote locations, with improved sensitivity and specificity, and the ability to maintain nucleic acid integrity for extended periods at ambient temperatures.

Implementation Method 1

The present invention is defined in the appended claims. Other disclosures are not part of the invention.

Methodology Applied
Scientific EffectPolymerase chain reaction (PCR):

Implementation Method 2

a chelating agent selected from the group consisting of ethylene glycol tetraacetic acid, hydroxyethylethylenediamine triacetic acid, diethylene triamine pentaacetic acid, N,N-bis(carboxymethyl)glycine, ethylenediaminetetraacetic, citrate anhydrous, sodium citrate, calcium citrate, ammonium citrate, ammonium bicitrate, citric acid, diammonium citrate, potassium citrate, magnesium citrate, ferric ammonium citrate, lithium citrate, and any combination thereof

Methodology Applied
Scientific EffectChelation:

Implementation Method 3

a buffer selected from the group consisting of tris(hydroxymethyl) aminomethane (Tris), citrate, 2-(N-morpholino)ethanesulfonic acid (MES), N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), 1,3-bis(tris(hydroxymethyl) methylamino)propane (Bis-Tris), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 3-(N-morpholino)propanesulfonic acid (MOPS), N,N-bis(2-hydroxyethyl) glycine (Bicine), N-[tris(hydroxymethyl)methyl]glycine (Tricine), N-2-acetamido-2-iminodiacetic acid (ADA), N-(2-acetamido)-2-aminoethanesulfonic acid (ACES), piperazine-1,4-bis(2-ethanesulfonic acid) (PIPES), bicarbonate, phosphate, and any combination thereof

Methodology Applied
Scientific EffectBuffering:

Data Source

PatentEP3581662A1Compositions and methods for detecting and identifying nucleic acid sequences in biological samples
Publication Date: 2019.12.18 LONGHORN VACCINES & DIAGNOSTICS LLC
  • EP3581662A1 patent drawingFigure 1~2
  • EP3581662A1 patent drawingFigure 3~4
  • EP3581662A1 patent drawingFigure 5~6

AI summary

The invention is directed to compositions and methods for isolating, detecting, amplifying, and quantitating pathogen-specific nucleic acids in a biological sample. The invention also provides diagnostic kits containing specific amplification primers, and labeled detection probes that specifically bind to the amplification products obtained therefrom. Also disclosed are compositions and methods for the isolation and characterization of nucleic acids that are specific to one or more pathogens, including for example Influenza virus and Mycobacterium tuberculosis, from a wide variety of samples including those of biological, environmental, clinical and/or veterinary origin.