Raman Spectral Ratio Detection of KMT2A-Rearranged ALL
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic methods for acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement are costly, invasive, and require specialized equipment and personnel, making early diagnosis in non-reference medical facilities challenging, especially for the infant population with poor treatment outcomes.
Innovation Solution
A Raman spectroscopy-based method that involves fixing lymphoblast samples with aldehyde and calculating the integral intensity ratio of 1040 cm⁻¹ to 1008 cm⁻¹ bands in Raman spectra to identify KMT2A gene rearrangement, enabling rapid, non-invasive, and low-cost diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional diagnostic methods (flow cytometry, molecular tests, genetic tests) are used to identify KMT2A gene rearrangement in ALL, then diagnostic accuracy and reliability are improved, but device complexity, cost, and requirement for specialized personnel increase
Solution Approach 1:
The patent replaces complex molecular biology equipment and procedures with Raman spectroscopy, an optical-based technique. Instead of using flow cytometry machines, PCR amplifiers, or next-generation sequencing platforms, the invention uses a Raman spectrometer to directly detect biochemical signatures of KMT2A rearrangement in lymphoblasts, substituting mechanical and chemical complex systems with a simpler optical detection method
Solution Approach 2:
The invention changes the diagnostic parameter from molecular genetic detection (requiring DNA extraction, amplification, and sequencing) to vibrational spectral analysis. By measuring Raman shifts at specific wavenumbers (794 cm⁻¹, 1040 cm⁻¹, 1008 cm⁻¹, 1450 cm⁻¹) and calculating intensity ratios, the method transforms an complex molecular diagnostic problem into a simpler spectroscopic measurement that can be performed with minimal sample preparation
2Reliability
If molecular and genetic tests are performed to determine leukemia subtypes, then treatment personalization and prognosis prediction are improved, but loss of time and increased cost occur
Solution Approach 1:
The patent applies preliminary biochemical fixation of lymphoblasts with glutaraldehyde, which preserves the biochemical signatures of KMT2A rearrangement and stabilizes the samples for later analysis. This preliminary action allows samples to be prepared in advance without requiring immediate molecular testing, enabling time-efficient diagnostics while maintaining diagnostic accuracy for treatment personalization
Solution Approach 2:
The invention replaces time-consuming molecular testing procedures (DNA extraction, PCR amplification, gel electrophoresis, or sequencing) with rapid Raman spectroscopic measurement. The spectroscopic method provides immediate spectral data that can be analyzed in real-time, dramatically reducing the time from sample collection to diagnostic result while still enabling treatment personalization based on KMT2A rearrangement detection
3Measurement precision
If invasive bone marrow aspiration and complex immunophenotyping are used for ALL diagnosis, then measurement precision and subtype identification are improved, but ease of operation and patient burden increase
Solution Approach 1:
The patent extracts and analyzes only the essential Raman spectral features from lymphoblasts that are specific to KMT2A rearrangement. By focusing on four key wavenumbers (794 cm⁻¹, 1040 cm⁻¹, 1008 cm⁻¹, 1450 cm⁻¹) and their intensity ratios, the method extracts the critical diagnostic information needed for subtype identification without requiring comprehensive immunophenotyping panels or complex morphological assessments
Solution Approach 2:
The invention uses Raman spectroscopy as an intermediary technique that bridges the gap between simple sample preparation and complex molecular diagnosis. The spectroscopic method acts as a mediator that provides molecular-level diagnostic information with minimal sample preparation, eliminating the need for invasive procedures and complex laboratory workflows while maintaining high measurement precision for ALL subtype identification
Data Source
Figure 1~2
Figure 3
AI summary
A method of identifying the ALL molecular subtype with rearrangements within the KMT2A gene was disclosed, which consists in measuring the ratio of the intensity of the Raman 1040/1008 cm-1 Raman bands in leukemia cells (lymphoblasts) isolated from the peripheral blood (when blastosis >90%) or bone marrow of patients during the diagnosis of acute lymphoblastic leukemia, and fixed with an aldehyde reagent.