Cell Depletion Microfluidic Device for HIV Viral Load
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Solution Overview
Problem
Current methods for HIV-1 viral load testing in resource-limited settings face challenges due to interference from proviral DNA and intracellular viral RNA in dried blood spots, and there is a poor correlation in viral load measurements between whole blood and plasma samples, especially at low titers, making it difficult to achieve accurate quantification.
Innovation Solution
A method and device for conducting quantitative analysis of whole blood samples using a device with a surface immobilized with anti-viral or anti-tumor cell surface marker antibodies, allowing for cell depletion without lysing cells, resulting in a depleted sample with less than 5% cells with the cell surface marker, which can then be used for viral or tumor load measurement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If whole blood samples are used for viral load testing, then sample collection is simplified and point of care testing is enabled, but proviral DNA and intracellular viral RNA in white blood cells interfere with accurate RNA quantification
Solution Approach 1:
The invention extracts and removes white blood cells containing proviral DNA and intracellular viral RNA from the whole blood sample through a depletion step, separating the interfering cellular components from the plasma where cell-free viral RNA is measured, thereby eliminating the source of interference while maintaining the ease of whole blood collection
Solution Approach 2:
The microfluidic device segments the whole blood sample into different components through controlled flow paths, separating white blood cells from plasma through the depletion chamber, allowing differential processing where cells are removed while plasma containing the target analyte proceeds to detection
2Measurement precision
If cell surface marker depletion is performed to remove white blood cells, then interference from proviral DNA is reduced, but the device complexity increases with multiple processing steps
Solution Approach 1:
The invention merges multiple functions (sample introduction, cell depletion, plasma separation, and nucleic acid detection) into a single integrated microfluidic device with continuous flow processing, eliminating the need for separate manual processing steps and reducing overall device complexity despite the multiple functional zones required
Solution Approach 2:
The microfluidic device performs multiple functions within a single platform: it introduces whole blood samples, depletes white blood cells using cell surface marker antibodies, separates plasma, and detects viral RNA, making the device universally applicable for point of care viral load testing without requiring additional specialized equipment
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 enables accurate and quantitative viral or tumor load measurement in whole blood samples, achieving correlation with plasma measurements and a limit of detection of less than 100 copies/mL, improving diagnostic accuracy in resource-limited settings.
Implementation Method 1
adding the whole blood sample to a device or a component thereof that does not include a filter, wherein the device or component includes a surface including immobilized anti-viral or anti-tumor cell surface marker antibodies
Data Source
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AI summary
The disclosure provides methods, devices, and kits for conducting a quantitative analysis of a whole blood sample. Various modifications to the disclosed methods, devices, and kits are described.