Molecular Rotor Fluorescence for RBC Deformability Profiling
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Solution Overview
Problem
Current diagnostic tests for pathologies associated with red blood cell (RBC) deformability alterations, such as sickle cell anemia, atherosclerosis, diabetes, malaria, and Alzheimer's, lack accuracy and practicality, failing to provide reliable vaso-occlusive risk estimation due to reliance on average indicators that obscure large dispersions in RBC properties.
Innovation Solution
Employing molecular rotors (MRs) that penetrate RBC membranes to measure fluorescence intensity and distribution, allowing for precise assessment of RBC deformability and viscosity, using trans-4-[4-(Dimethylamino)styril]-1-methylpyridinium (tDASMP) or chemically modified versions to detect alterations and predict pathology risk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If molecular rotors are used to measure intracellular viscosity, then measurement precision is improved, but device complexity increases
Solution Approach 1:
Molecular rotors serve as intermediary probes that penetrate RBC membranes to measure intracellular viscosity. These fluorescent molecules interact with the intracellular environment and provide readable signals that reflect RBC deformability, enabling precise measurements without complex invasive procedures
Solution Approach 2:
The patent replaces complex mechanical ektacytometry systems with a simpler fluorescent-based optical system. Instead of using light diffraction through shear flow and complex mechanical apparatus, the invention uses molecular rotor fluorescence intensity to directly indicate intracellular viscosity and RBC deformability
2Measurement precision
If ektacytometry is used to measure RBC deformability, then measurement capability is provided, but manufacturing precision and result reliability deteriorate due to sensitivity to methodology variability
Solution Approach 1:
The patent changes the measurement parameter from macroscopic light diffraction patterns to molecular-level fluorescent intensity. By using molecular rotors whose fluorescence quantum yield directly correlates with intracellular viscosity, the method achieves more reliable and reproducible measurements that are less sensitive to operational variability
3Quantity of substance
If average HbS level is measured, then diagnostic information is obtained, but measurement precision of individual RBC properties deteriorates due to obscuring large dispersions
Solution Approach 1:
The patent segments the measurement from population-averaged HbS levels to individual RBC-level deformability assessment. By treating each RBC as an independent measurement unit through fluorescent probe penetration, the method reveals the distribution of deformability properties across individual cells rather than providing a single averaged value
4Measurement precision
If complex diagnostic equipment is used, then measurement capability is improved, but ease of operation deteriorates due to difficulty in clinical implementation
Solution Approach 1:
The molecular rotors are designed to spontaneously penetrate RBC membranes and self-assemble within cells without requiring complex sample preparation or external assistance. The probes automatically distribute themselves in the intracellular environment and provide readings that reflect the native physiological state of RBCs
Solution Approach 2:
The patent uses fluorescent color intensity changes as a direct readout of intracellular viscosity. The molecular rotors exhibit fluorescence quantum yield variations that correlate with RBC deformability, providing a simple optical signal that can be detected with standard fluorescence microscopy or flow cytometry 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
Provides a high-throughput, simple diagnostic test capable of accurately determining RBC deformability distribution and vaso-occlusive risk, offering a new biomarker for clinical management with improved sensitivity and specificity.
Implementation Method 1
mixing the blood sample containing red blood cells to be tested with a molecular rotor (MR) able to penetrate RBCs cell membrane; quantifying the level of fluorescent signal emitted by the molecular rotor
Implementation Method 2
The fluorescence intensity is directly proportional to the intracellular viscosity, allowing to precisely determine the deformability of individual red blood cells
Data Source
AI summary
The present invention is directed to a method to detect in a blood sample whether the red blood cells (RBCs) contained in said blood sample present or not an alteration of their deformability by using molecular rotor (MR) able to penetrate RBCs cell membrane. The invention also relates to diagnostic methods of RBC related pathologies associated to the modification of the distribution of the viscosity, rigidity or deformability of RBCs by detection and measurement of the RBCs fluorescence intensity image intensity implementing optical methods. Finally, the present invention is directed to the use of MRs for testing the deformability of red blood cells (RBCs) in a blood sample and kit comprising MR and red blood cells (RBCs) control.