Saliva Diagnostic Device Nucleic Acid Capture Enzymatic Readout
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Solution Overview
Problem
Current methods for diagnosing infectious diseases, such as COVID-19, are limited by the need for centralized laboratories, expensive instrumentation, and require skilled personnel, making them unsuitable for rapid and reliable at-home testing. Existing alternatives like CRISPR-based and LAMP-based assays are inefficient, less sensitive, and less accurate.
Innovation Solution
A device with a first chamber for releasing nucleic acids from a sample and a second chamber containing enzyme-conjugated beads attached via single-stranded oligonucleotides, allowing for nucleic acid capture and detection without extraction or amplification, enabling rapid and accurate detection of infectious agents in bodily fluids like saliva.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If RT-PCR based testing is used, then detection accuracy is improved, but device complexity and requirement for centralized laboratory equipment increases
Solution Approach 1:
The invention extracts the nucleic acid detection function from complex RT-PCR laboratory equipment and implements it in a simplified device architecture. The device separates sample processing (first chamber) from detection (second chamber), eliminating the need for expensive instrumentation while maintaining detection accuracy through targeted nucleic acid capture and enzymatic amplification.
Solution Approach 2:
The device is divided into distinct functional segments: a first chamber for sample preparation and nucleic acid release, and a second chamber for nucleic acid capture and detection. This segmentation allows each component to be optimized independently, reducing overall device complexity while preserving measurement precision.
2Measurement precision
If respiratory swab specimens are collected, then detection sensitivity is improved, but ease of operation deteriorates due to discomfort and skill requirements
Solution Approach 1:
The invention extracts the detection target from difficult-to-obtain respiratory swabs and shifts it to easily collectable saliva samples. By designing the device to detect viral nucleic acids present in saliva, it eliminates the discomfort and skill requirements associated with respiratory swab collection while maintaining detection sensitivity through appropriate nucleic acid capture mechanisms.
3Measurement precision
If CRISPR-based STOP assay is used, then detection accuracy is improved, but duration of action increases to at least 45 minutes
Solution Approach 1:
The device performs preliminary actions by pre-loading the second chamber with capture probes and enzymatic reagents before sample introduction. This preparation allows the detection process to proceed rapidly upon sample addition, reducing overall test duration while maintaining the accuracy benefits of CRISPR-based detection methods.
Solution Approach 2:
The detection process utilizes periodic enzymatic reactions that occur in discrete steps within the second chamber, allowing for rapid amplification and detection cycles that reduce total test time compared to continuous incubation methods while preserving detection accuracy.
4Productivity
If LAMP-based approach with heat block is used, then productivity is improved with 30 minute detection, but ease of operation worsens due to temperature control requirements
Solution Approach 1:
The device employs self-service mechanisms where the enzymatic reactions in the second chamber automatically proceed at optimal temperatures without external heating control. The biological systems within the device self-regulate the reaction conditions, eliminating the need for user-operated heat blocks while maintaining fast detection speeds.
5Ease of operation
If LFIAs are used, then ease of operation is improved, but measurement precision deteriorates with reduced sensitivity and accuracy
Solution Approach 1:
The invention replaces the mechanical/chemical antibody-antigen binding mechanism of LFIAs with a nucleic acid-based detection system. This substitution enables the device to maintain the portability and ease of operation of lateral flow assays while achieving the higher sensitivity and accuracy of molecular diagnostic methods through nucleic acid amplification and specific probe binding.
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 quick, efficient, and sensitive detection of infectious agents at home or in point-of-care settings, reducing the need for laboratory equipment and skilled personnel, and improving the speed and accuracy of diagnosis.
Implementation Method 1
the single stranded oligonucleotide comprises a first sequence corresponding to a restriction site of the at least one restriction enzyme and a second sequence complementary to a fragment of the nucleic acid of the infectious agent
Implementation Method 2
the second chamber comprising a nucleic acid capture portion, a readout generation portion, and second solution including at least one restriction endonuclease enzyme
Data Source
AI summary
Provided herein are compositions and devices for diagnosing and treating a viral infection in a subject and/or detecting a viral nucleic acid in a sample. In one example, a sample is treated in a first chamber and the sample is flowed into a second chamber, where any pathogenic nucleic acid is detected by oligonucleotides that are specific to the pathogen under test. Further, the oligonucleotides comprise a cleavage site for a restriction enzyme in the second chamber, which cleaves oligonucleotide-pathogenic nucleic acid hybrid resulting in the exposure of an enzyme that was being held by the oligonucleotide to its substrate, which generates a colorimetric and/or another visual readout.