Ion-Exchange Concentration for TB-LAM Rapid Detection
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Solution Overview
Problem
Current rapid diagnostic tests for tuberculosis are inefficient and lack accuracy, particularly for point-of-care settings, due to low sensitivity and frequent false positives, especially in detecting tuberculosis-lipoarabinomannan (TB-LAM) in urine samples, which is a virulence factor associated with Mycobacterium tuberculosis.
Innovation Solution
A method involving the concentration of TB-LAM from urine samples using an ion-exchange medium to create a concentrated eluate, which is then loaded into a rapid diagnostic testing device with a TB-LAM-specific antibody, enhancing the binding efficiency and sensitivity of the test under high salt concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional rapid diagnostic tests are used to detect TB-LAM in urine samples, then the test can be performed quickly and independently of laboratory equipment, but the sensitivity is low and false positives are frequent
Solution Approach 1:
The patent applies preliminary action by concentrating TB-LAM from urine samples before performing the rapid diagnostic test. The method involves contacting the urine sample with an ion-exchange medium to capture TB-LAM, then eluting it with a high salt concentration buffer to create a concentrated eluate. This pre-concentration step increases the antigen concentration to levels detectable by rapid diagnostic tests, thereby improving sensitivity and reducing false positives while maintaining the simplicity and speed of the test format
Solution Approach 2:
The patent applies parameter changes by utilizing high salt concentration (greater than 150 mM, preferably greater than 500 mM) to enable TB-LAM binding to the antibody in the rapid diagnostic test. This parameter change allows the test to function effectively with concentrated samples and improves detection accuracy. The high salt concentration buffer is used both for elution from the ion-exchange medium and for the subsequent binding reaction, creating optimal conditions for sensitive and specific detection
2Quantity of substance
If sample concentration is performed using prior methods, then the biomolecule concentration increases, but the process requires extensive sample processing and manipulation making it complex and cumbersome
Solution Approach 1:
The patent merges the concentration function with the rapid diagnostic test device itself. The ion-exchange medium is integrated into the test strip or cassette format, allowing sample preparation and detection to occur in a single integrated device. This eliminates the need for separate, complex concentration equipment and procedures, making the process simple and suitable for field use while achieving 2× to 25× concentration of TB-LAM
Solution Approach 2:
The patent applies self-service by designing the rapid diagnostic test device to perform its own sample concentration function. The ion-exchange medium within the device automatically concentrates TB-LAM from the urine sample as it passes through, without requiring external concentration equipment or complex manual manipulation. The device self-regulates the concentration process through its integrated ion-exchange and elution mechanism
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
This approach significantly increases the concentration of TB-LAM, improving the sensitivity of rapid diagnostic tests and reducing false positives, enabling early and accurate detection of tuberculosis, even at low antigen levels, and is effective for diagnosing extra-pulmonary mycobacterial infections.
Implementation Method 1
contacting the source biological sample to an ion-exchange medium comprising one or more ligands to capture the biomolecule and form a captured-biomolecule
Implementation Method 2
eluting the captured-biomolecule from the ion-exchange medium as an eluate... The solution has a salt concentration greater than 150 mM
Implementation Method 3
loading the eluate to a rapid diagnostic testing device comprising an antibody... The biomolecule binds to the antibody under the salt concentration of greater than 150 mM
Data Source
AI summary
A rapid detection method of a target biomolecule comprising an antigenic moiety is provided. The method includes providing a source biological sample comprising the target biomolecule; contacting the source biological sample to an ion-exchange medium; eluting the captured-target biomolecule from the ion-exchange medium as an eluate, and loading the eluate to a rapid diagnostic testing device comprising an antibody. The eluate comprises a concentrated form of the biomolecule in a solution having a salt concentration greater than 150 mM. A concentration of the target biomolecule in the eluate is in a range from about 2× to 25× compared to a concentration of the biomolecule in the source biological sample. The target biomolecule binds to the antibody under the salt concentration of greater than 150 mM. A device for rapid detection of target biomolecule is also provided.