Quantum Cascade Laser Mid-IR Spectroscopy for Label-Free Cell Sorting

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Solution Overview

Problem

Current methods for cell sorting, such as fluorescence-activated cell sorting (FACS), face challenges including low accuracy, safety concerns, and damage to cells due to high-energy UV light and chemical markers, while mid-IR spectroscopy is limited by strong water absorption and scattering issues.

Innovation Solution

The use of quantum cascade lasers (QCLs) for mid-infrared absorption measurements, which allow for label-free, high-speed sorting of cells by inducing resonant mid-IR absorption and detecting transmitted light to identify cell characteristics, minimizing photon damage and scattering effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fluorescence-activated cell sorting (FACS) is used to sort cells, then cell sorting capability is achieved, but cell damage occurs due to high-energy UV light and chemical markers

Engineering Contradiction:

Improvecell sorting accuracyVSAvoidcell damage from UV light and chemical markers

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the wavelength parameter from UV/visible range (used in FACS) to mid-infrared range (3-15 microns). This parameter change allows direct detection of molecular vibrations in DNA and proteins without requiring fluorescent markers or high-energy photons, thereby eliminating marker-induced chromosomal damage and reducing photon-induced damage while maintaining sorting accuracy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts and eliminates the harmful components from the cell sorting system: fluorescent chemical markers and high-energy UV light sources are removed entirely. The system achieves cell identification and sorting using only mid-infrared light that directly probes molecular vibrations, taking out the problematic elements that cause cell damage while preserving the sorting function.

Inventive Principle:

Principle #2Taking out (Extraction)

2Measurement precision

If mid-IR spectroscopy is used for cell analysis, then label-free detection is achieved, but strong water absorption and scattering reduce measurement accuracy

Engineering Contradiction:

Improvelabel-free cell detection accuracyVSAvoidwater absorption and light scattering

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent transitions from traditional transmission-mode spectroscopy to reflection-mode spectroscopy, changing the measurement dimension. By detecting reflected mid-infrared light from cells rather than transmitted light, the system overcomes water absorption limitations and scattering issues, enabling accurate label-free detection despite the presence of water in biological samples.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Productivity

If FACS uses high-intensity UV laser and fluorescent markers to achieve cell sorting, then sorting speed can be increased, but measurement accuracy decreases due to scattering and absorption

Engineering Contradiction:

Improvecell sorting speedVSAvoidquantitative measurement accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent replaces the complex FACS mechanical and chemical system (fluorescent markers, UV lasers, fluidics) with a simpler mid-infrared optical system. The QCL-based mid-IR spectroscopy directly measures molecular vibrations without requiring markers or complex fluorescence detection, enabling both high-speed operation and accurate quantitative measurements of DNA and protein content.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 accurate, high-throughput cell sorting with reduced risk of cell damage, achieving purities of over 99% for gender selection and other applications, while maintaining cell viability and efficiency.

Implementation Method 1

delivering QCL light to a single cell to induce resonant mid-IR absorption by one or more analytes of the cell

Methodology Applied

Scientific EffectResonant mid-IR absorption: Absorption (EM radiation)

Implementation Method 2

induce bond vibrations in the sperm cell DNA, and detecting the signature of the bond vibrations

Methodology Applied

Scientific EffectBond vibrations: Vibration

Data Source

PatentUS10175159B2Use of vibrational spectroscopy for DNA content inspection

Publication Date: 2019.01.08 1087 SYST

AI summary

This disclosure concerns a cytometry system including a handling system that enables presentation of single cells to at least one laser source. The laser source is configured to deliver light to a cell within the cells in order to induce bond vibrations in the cellular DNA. The system further includes a detection facility that detects the signature of the bond vibrations, wherein the bond vibration signature is used to determine the folding or packing of the DNA.