Biomarker Detection for Tuberculosis Diagnosis
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Solution Overview
Problem
Current methods for diagnosing tuberculous meningitis (TBM) are inadequate due to low sensitivity and specificity, long turnaround times, and high operational costs, particularly in resource-limited settings, leading to delayed diagnosis and poor outcomes.
Innovation Solution
A method and device for diagnosing tuberculosis by testing biological samples for the presence of CC4 and other biomarkers such as CC4b, procalcitonin, CCL1, apolipoprotein-CIII, RANTES, and TNF-α using capture agents and indicators, which can be used in various samples including CSF, saliva, and blood, and a kit for performing this method.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mycobacterial culture is used for diagnosis, then sensitivity is improved (60-70%), but turnaround time increases (2-6 weeks)
Solution Approach 1:
The patent performs preliminary concentration and enrichment of M. tuberculosis from large volumes of CSF (1-10 mL) before culture, which accelerates the growth phase and reduces the overall turnaround time while maintaining high sensitivity through pre-concentration of the pathogen
2Measurement precision
If Xpert MTB/RIF Ultra is used for diagnosis, then sensitivity is improved (higher than initial Xpert and culture), but operational cost and infrastructural requirements increase
Solution Approach 1:
The patent extracts and concentrates M. tuberculosis from large volumes of CSF (1-10 mL) into a small volume concentrate, enabling the use of simpler, less expensive diagnostic tests on the concentrated sample rather than requiring complex molecular amplification systems on large volumes of dilute CSF
Solution Approach 2:
The patent employs disposable microcentrifuge tubes and simple centrifugation equipment instead of expensive, complex molecular diagnostic systems, making the approach suitable for resource-limited settings while achieving comparable or superior sensitivity
3Loss of time
If initial Xpert MTB/RIF test is used for diagnosis, then turnaround time is improved (2 hours), but sensitivity is reduced (50-60%)
Solution Approach 1:
The patent performs preliminary concentration and enrichment of M. tuberculosis from large volumes of CSF (1-10 mL) before testing, which increases the bacterial load in the test sample and thereby improves the sensitivity of rapid molecular tests like Xpert MTB/RIF while maintaining the rapid 2-hour turnaround time
4Productivity
If microscopy is used for diagnosis, then cost is reduced and speed is improved, but sensitivity is severely reduced (~10-15%)
Solution Approach 1:
The patent performs preliminary concentration and enrichment of M. tuberculosis from large volumes of CSF (1-10 mL) into a small volume concentrate, which increases the bacterial load to levels detectable by microscopy, thereby maintaining the speed and low cost of microscopy while dramatically improving its sensitivity
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
The method provides rapid and accurate diagnosis of TBM with high sensitivity and specificity, reducing the risk of misdiagnosis and overtreatment, and is suitable for use in resource-limited settings with a point-of-care device.
Implementation Method 1
testing a biological sample from a subject for the presence of CC4 and at least one other capture agent which binds to a biomarker selected from the group consisting of CC4b, procalcitonin, CCL1, apolipoprotein-CIII, RANTES and TNF-α
Data Source
AI summary
A method of diagnosing tuberculosis (TB) is provided. The method comprising the step of testing a biological sample from the subject for the presence of CC4 and at least one other biomarker selected from the group consisting of CC4b, procalcitonin, CCL1, apolipoprotein-CIII, RANTES and TNF-α. A device, kit and computer-implemented method for diagnosing (and optionally also treating) TB are also provided.