Volumetric Absorptive Microsampling for Non-Invasive DNA Mutation Detection
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Solution Overview
Problem
Current methods for detecting hereditary cancer-related mutations in patients are cumbersome, invasive, and require large blood volumes, making them unsuitable for critically ill patients and inefficient for rapid, non-invasive risk assessment of breast, ovarian, colon, and skin cancers.
Innovation Solution
A method using a volumetric absorptive microsampling device to collect small-volume dried biological fluid samples, which are then processed for genomic DNA extraction and high-throughput massive parallel sequencing to detect mutations in specific hereditary cancer-related genes, allowing for the selection of appropriate therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional blood collection methods are used to detect hereditary cancer mutations, then sufficient DNA can be obtained for sequencing, but the procedure becomes invasive and requires large blood volumes that critically ill patients cannot provide
Solution Approach 1:
The patent extracts only the essential component (DNA) from a minimal blood sample using a microsampling device that collects approximately 10-20 μL of blood, far less than traditional methods. This extraction approach allows sufficient DNA recovery for NGS while minimizing the invasive blood draw required from critically ill patients.
Solution Approach 2:
The patent changes the sample volume parameter from milliliters (traditional blood draw) to microliters (microsampling device), enabling DNA extraction and mutation detection with a fraction of the blood volume previously required, thus reducing invasiveness while maintaining diagnostic capability.
2Quantity of substance
If traditional nucleic acid extraction procedures are used, then sufficient DNA can be obtained for analysis, but the procedures become cumbersome and require specialized equipment or technical skill
Solution Approach 1:
The patent uses a specialized microsampling device with an absorbent tip that directly captures and preserves DNA in a stabilized format, eliminating the need for complex extraction equipment. The device itself performs the extraction function, requiring only simple elution with buffer or water to release DNA for sequencing.
Solution Approach 2:
The microsampling device with absorbent tip is designed to self-perform sample collection, stabilization, and preservation functions. The absorbent material inherently stabilizes DNA without requiring additional reagents or equipment, making the system self-sufficient and eliminating dependencies on specialized laboratory infrastructure.
3Loss of time
If rapid mutation detection is implemented for critical care patients, then treatment decisions can be made quickly, but the sample collection must be non-invasive and require minimal blood volume
Solution Approach 1:
The microsampling device is pre-prepared with absorbent tip material that is ready to immediately stabilize and preserve DNA upon blood contact. This preliminary preparation allows rapid sample collection and stabilization without requiring subsequent complex processing steps, enabling quick turnaround for critical care decision-making.
Solution Approach 2:
The patent changes the sample volume parameter to microliter scale while maintaining DNA quality sufficient for NGS. This parameter change enables rapid processing of minimal samples, reducing both the time required for analysis and the invasive blood draw volume, making it suitable for critically ill patients who need quick, non-invasive testing.
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 rapid, non-invasive detection of hereditary cancer-related mutations in small samples, facilitating personalized treatment decisions for patients with breast, ovarian, colon, and skin cancers, even in critically ill individuals.
Implementation Method 1
an absorbent tip configured to absorb approximately 10-20 μL of blood within approximately 10 seconds
Implementation Method 2
elution of the dried biological fluid sample is performed by contacting the absorbent tip of the microsampling device with the lysis buffer for up to 15 minutes at 90 °C
Implementation Method 3
elution of the dried biological fluid sample is performed by contacting the absorbent tip of the microsampling device with Proteinase K for up to 1 hour at 56 °C
Data Source
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AI summary
The present disclosure provides rapid and non-invasive methods for determining whether a patient exhibiting cancer symptoms, or at risk for hereditary cancers such as breast cancer, ovarian cancer, colon cancer, or skin cancer, will benefit from treatment with one or more therapeutic agents. These methods are based on detecting hereditary cancer-related mutations in small-volume dried biological fluid samples that are collected using a volumetric absorptive microsampling device (e.g., MITRA Tip). Kits for use in practicing the methods are also provided.