Microfluidic Aptamer Isolation for MRD Detection

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Solution Overview

Problem

Current methods for detecting minimal residual disease (MRD) in multiple myeloma, such as multiparameter flow cytometry and serum-based techniques, face limitations including poor sensitivity, invasiveness, and batch-to-batch variability, which hinder frequent and accurate monitoring.

Innovation Solution

The development of a microfluidic device for isolating and amplifying aptamers that target M-Ig proteins using a systematic evolution of ligands by exponential enrichment (SELEX) process, enabling sensitive and specific detection of MRD through affinity selection and bead-based PCR amplification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If serum-based methods (SPEP, IFE, FLC) are used for MRD detection, then the detection can be performed non-invasively, but the sensitivity is low with LOD of 500-2000 mg/L

Engineering Contradiction:

Improvenon-invasive detectionVSAvoidsensitivity

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses aptamers as intermediary molecules that specifically bind to M-Ig proteins in serum. These aptamers act as mediators between the serum sample and the detection system, enabling highly sensitive detection of MRD through their specific binding interactions while maintaining the non-invasive nature of serum-based testing.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from conventional protein quantification methods to aptamer-based binding detection. By using aptamers with high affinity and specificity for M-Ig proteins, the detection limit is improved from 500-2000 mg/L to potentially lower concentrations, achieving both non-invasive operation and high sensitivity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If conventional aptamer isolation methods are used, then aptamers can be obtained from randomized oligomer libraries, but the process is time-consuming and lacks standardization

Engineering Contradiction:

Improveaptamer specificityVSAvoidisolation time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent merges the selection and isolation steps into a single integrated microfluidic device. The device combines affinity selection chambers with on-chip amplification and detection capabilities, eliminating the need for separate, time-consuming off-chip processing steps and enabling standardized, rapid aptamer isolation.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device enables self-contained aptamer isolation where all necessary operations (selection, washing, amplification, detection) are performed within the chip itself. This self-service capability eliminates the need for external equipment and manual intervention at each step, reducing isolation time and improving standardization.

Inventive Principle:

Principle #25Self-service

3Measurement precision

If bone marrow aspirate analysis is performed, then MRD can be detected with good sensitivity, but the procedure is invasive and prohibits frequent monitoring

Engineering Contradiction:

ImproveMRD detection sensitivityVSAvoidinvasiveness

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent creates a copy of the bone marrow detection capability using serum samples. Instead of directly analyzing bone marrow cells, the method detects M-Ig proteins in serum that serve as copies or markers of the disease state, enabling indirect but equally sensitive monitoring through non-invasive blood draws.

Inventive Principle:

Principle #26Copying

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 allows for the rapid and cost-effective isolation of high-affinity aptamers that can detect M-Ig proteins with enhanced sensitivity, facilitating personalized and non-invasive MRD monitoring in multiple myeloma patients, improving clinical management by providing sensitive and specific assays.

Implementation Method 1

introducing a first group of oligomers including at least an M-Ig targeting oligomer into the first selection chamber, such that the M-Ig targeting oligomer binds to the first sample of M-Ig proteins

Methodology Applied

Scientific EffectMolecular recognition:

Implementation Method 2

removing unbound oligomers of the first sample from the first selection chamber to isolate the M-Ig targeting oligomer

Methodology Applied

Scientific EffectFiltration: Filter (physical)

Data Source

PatentUS10294471B2Method of isolating aptamers for minimal residual disease detection

Publication Date: 2019.05.21 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

A method for selecting and isolating aptamers that target M-Ig proteins with a microdevice including at least a first selection chamber is provided. The method includes preparing a first sample of M-Ig proteins from a serum; placing the M-Ig proteins in the first selection chamber; introducing a first group of oligomers including at least an M-Ig targeting oligomer into the first selection chamber, whereby the M-Ig targeting oligomer binds to the first sample of M-Ig proteins. The method further includes removing unbound oligomers of the first sample from the first selection chamber to isolate the M-Ig targeting oligomer.