NIR-II Rare Earth Nanoprobe Test Strip for Tumor Biomarker Detection
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Solution Overview
Problem
Current fluorescence-based lateral flow assays for tumor biomarker detection face challenges with poor optical stability, photobleaching, and interference from tissue autofluorescence, leading to low signal-to-noise ratios and limited sensitivity, especially in the near infrared-I region.
Innovation Solution
Development of a near infrared-II region (NIR-II) fluorescent rare earth nanoprobe test strip with rare earth nanoprobes (RENPs) that utilize a plastic backing, sample pad, conjugation pad, nitrocellulose membrane, and absorbent pad, where detection antibodies labeled with RENPs are immobilized on the conjugation pad and capture antibodies are sprayed on the nitrocellulose membrane, offering improved luminescence properties and deeper tissue penetration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorescent materials (fluorescent dyes, quantum dots, time-resolved fluorescent microspheres) are used in lateral flow immunoassay, then the detection sensitivity is improved compared to traditional LFA, but the optical stability is poor, photobleaching occurs easily, and photodegradation happens, leading to low signal-to-noise ratio
Solution Approach 1:
The patent changes the emission wavelength parameter from visible light region (400-700 nm) or near infrared-I region (700-900 nm) to near infrared-II region (900-1700 nm). This parameter change eliminates tissue autofluorescence interference and improves optical stability, as the NIR-II region has negligible autofluorescence from biological samples and reduced photobleaching effects
Solution Approach 2:
The patent uses composite material structure with core-shell design where rare earth nanoparticles (NaYF4:Yb3+, Er3+ or NaYF4:Yb3+, Nd3+) are coated with silica shell and further functionalized with antibodies. This composite structure protects the fluorescent core from photodegradation while maintaining high quantum yield and optical stability
2Measurement precision
If fluorescent materials with emission wavelength in visible light region (400-700 nm) or near infrared-I region (700-900 nm) are used, then fluorescence detection can be achieved, but tissue autofluorescence causes interference and spectra overlap occurs due to close excitation and emission wavelengths
Solution Approach 1:
The patent shifts the emission wavelength parameter to near infrared-II region (900-1700 nm), specifically achieving emission peaks at 1530-1560 nm for Er3+-doped nanoparticles. This parameter change moves the detection window to a region with negligible tissue autofluorescence, eliminating the harmful interference effect
Solution Approach 2:
The patent introduces Yb3+ as an intermediary sensitizer that absorbs excitation light at 980 nm and transfers energy to Er3+ or Nd3+ emitters. This intermediary mechanism enables efficient energy transfer while using excitation wavelength far from emission wavelength, avoiding spectra overlap
3Measurement precision
If conventional fluorescent probes are used in lateral flow assay, then the assay can be performed, but the fluorescence penetration is weak and quantum yield is relatively low, severely influencing the signal-to-noise ratio
Solution Approach 1:
The patent employs composite material system with rare earth-doped nanoparticle core (NaYF4:Yb3+, Er3+ or NaYF4:Yb3+, Nd3+) providing high quantum yield (up to 68% for Er3+ emission at 1530-1560 nm) and silica shell providing stability and functionalization capability. This composite structure achieves both high quantum yield and deep tissue penetration in NIR-II region
Solution Approach 2:
The patent changes the emission wavelength parameter to near infrared-II region (900-1700 nm) where biological tissues have minimal absorption and scattering. This parameter change enables deeper tissue penetration and reduces background noise, significantly improving signal-to-noise ratio
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
The NIR-II fluorescent rare earth nanoprobe test strip achieves accurate quantification, high stability, and favorable repeatability, enhancing detection sensitivity and accuracy for tumor biomarkers like CEA, suitable for rapid point-of-care testing.
Implementation Method 1
NIR-II fluorescent probes, growing interests have been focused on rare earth nanoprobes (RENPs) because of their large Stokes shifts, narrow and multi-peak emission profiles, negligible excitation-emission band overlap, long lifetime and excellent photostability
Implementation Method 2
The probe possesses fluorescent emission double peaks, and the central wavelength of the emission peak is 1064±15 nm and 1345±15 nm, respectively
Data Source
AI summary
A near infrared-II region (NIR-II) fluorescent rare earth nanoprobe (RENP) test strip and its preparation method are disclosed. The NIR-II fluorescent RENP test strip includes a sample pad, a conjugation pad, a nitrocellulose (NC) membrane, an absorbent pad and a plastic backing. The sample pad, conjugation pad, NC membrane, absorbent pad are superimposed on the plastic backing successively along a horizontal direction. Detection antibodies labeled RENPs are immobilized on the conjugation pad; capture antibodies set as a test line and quality control antibodies set as a control line are sprayed on the NC membrane. RENPs with NIR-II luminescence are selected as an efficient fluorescent probe, and its excellent optical properties make the prepared test strip possesses excellent detection sensitivity, good accuracy, high stability and favorable repeatability. Meanwhile, preparation process of test strip is also simple and controllable, which is suitable for scale production.