Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)
Abstract
:1. Introduction
2. MRD in Lung Cancer
3. Liquid Biopsy as an Alternative Technique for Tissue Biopsy
3.1. Circulating Cell-Free DNA (cfDNA) and Circulating Tumour DNA (ctDNA)
3.2. Circulating Tumor Cells (CTCs)
3.3. Extracellular Vesicles (EVs)
4. Type of Biosensors for Detection of Lung Cancer Biomarkers in Liquid Biopsy
4.1. Electrochemical Sensor
4.2. Electro-Kinetic Biosensors
4.3. Magnetic Biosensor
4.4. Optical Biosensors
4.4.1. Surface Enhanced Raman Spectroscopy (SERS)
4.4.2. Surface Plasmon Resonance Biosensors (SPR)
4.4.3. Fluorescence-Based Biosensing
4.4.4. Lateral Flow Immunoassay (LFIA)
4.4.5. Chemiluminescence
4.5. Other Biosensors
5. Challenges and Future Prospective of Liquid MRD
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Principle of Method | Advantages | Disadvantages | Application in MRD of Lung Cancer | |
---|---|---|---|---|
Traditional Biopsy and morphological-based test | A piece of lung tissue is taken from the body for histopathology evaluation. | Clinically validated | Invasive and risky. Unpleasant for the patient. Inter and intra laboratory error during reporting of the result. Failure to detect metastasis in other tissues. Serial sampling is challenging. Low sensitivity. | Traditional methods for MRD detection. Immunohistochemistry staining to identify and monitor biomarkers |
ddPCR | Digital PCR (dPCR) divides a bulk PCR reaction into millions of nanolitre-scale microreactions, each containing zero, one, or only a few DNA molecules. Absolute quantification of the material by dPCR is accomplished by counting positive nano responses and using Poisson statistics. | Costly; ultra-sensitive; no need for a calibrator for quantification. Absolut quantification; fast. | False-positive and negative results. Requires a skilled technician. Not routinely available in many clinical laboratories. Sophisticated instruments are required | It is an ultrasensitive method for detecting pre-defined mutations. MRD quantification and treatment monitoring are possible without the need for a calibrator curve. |
NGS | Next-generation sequencing (NGS) is a massively parallel sequencing technology to large-scale DNA sequencing. | Applicable to all known and new mutations. | Well-trained technicians are needed. Analysing the results is time-consuming. Costly, requires high DNA input, low sensitivity, rapid turnaround times. | Unlike other methods, it is possible to analyse at the genome-wide level. |
Biosensor | Simple; ultra-sensitivity; disposable test. Applicable as a POCT test. | Clinically not well validated. False result | As a new and low-cost method, it can perform tests at consecutive times. Different bioreceptors can detect MRD on liquid biopsy. As a POCT test, it is possible to perform the test at the bedside. |
Detection Method | Sample | Biomarkers | Biosensor | Limit of Defection (LoD) | References |
---|---|---|---|---|---|
Electrochemical | Synthetic lncRNAs | MALAT1 | SPCE | 42.8 fM | [40] |
Saliva and plasma | EGFR L858R and exon 19 del mutations | EFIRM | NA | [41] | |
Small extracellular vesicles (sEVs) | EGFR | Electrokinetic Sensor | 2.8 × 108 particles/mL | [42] | |
Serum and saliva | - | EFIRM | NA | [43] | |
Synthetic DNA | EGFR | sandwich-assays | NA | [44] | |
Serum | CYFRA21-1 and CEA | 3D graphene (3D-G), poly-thionine (pThi) and poly-m-Cresol purple (pMCP) | 0.18 ng/mL (CYFRA21-1) 0.31 ng/mL (CEA) | [45] | |
Serum | CYFRA21-1 | Microfluidic | 0.026 pg mL−1 | [46] | |
Serum | CYFRA 21-1 | ECL and eATRP signal amplification | 0.8 fg mL−1 | [47] | |
Exosomes | EGFR and PD-L1 | Electro-kinetic | 4.9 × 106 particles/mL | [48] | |
SPR | Exosomes miRNAs | miRNA-21, 378, 200, 139 | SPR | 1.68 fM | [49] |
Exosomes | Anti-EGFR and anti-EpCAM | SPRi | 2.37 × 104 particles/μL | [50] | |
Serum (Protein) | ALCAM, TAGLN2 | SPR imaging sensor with polarisation contrast | 6 ng/mL (ALCAM) 3 ng/mL (TAGLN2) | [51] | |
Exosomes | EGFR, PD-L1 | Nanoplasmonic exosome (nPLEX) assay | 9.258 × 103%/RIU | [52] | |
SERS | Serum | Cytochrome c (Cyt c) | Aptasensor | 1.79 pg/mL (Serum) 1.148 pg/mL (PBS) | [53] |
CTCs | EpCAM | antibody-adsorbed nitrocellulose membrane | NA | [54] | |
Fluorescence | Tumour-derived exosomes (Plasma) | IGF-1R | Microfluidic device | 0.28–0.38 pg/mL | [55] |
cell extracts | CDK6 Kinase | fluorescent peptide biosensor | NA | [56] | |
Magnetic | CTCs | EGFR | Immunomagnetic and Magnetic Sifter | NA | [57] |
Aptamer | Exosomes | Identification of A549 exosomes | lateral flow aptamer assay | 6.4 × 109 particles/mL | [58] |
Micronuclear magnetic resonance | CTCs | EGFR, EpCAM, HER-2, MUC-1 | μNMR | NA | [59] |
colorimetric | Serum | Monitoring soluble immune checkpoints (PD-L1, PD-1), (LAG-3) | microfluidic sandwich immunoassay (multiplexed immune checkpoint biosensor (MICB) | 5 pg mL−1 (PD-1 and PD-L1) 50 pg mL−1 (LAG-3) | [60] |
Transduce | Principle | Advantages | Disadvantages | Application in Lung Cancer MRD |
---|---|---|---|---|
Electrochemical sensor | Convert the biochemical interaction to electrical signals |
|
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Magnetic biosensor | Applying paramagnetic particles to detect biological interactions by monitoring magnetic property changes |
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Surface-enhanced Raman spectroscopy (SERS) | Using molecules adsorbing on rough metal surfaces to generate Raman scattering |
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Surface plasmon resonance biosensors (SPR) | Alteration of SPR angle due to increasing of refractive index during binding of biomolecules on the sensor surface |
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Fluorescence-based biosensing | An analytical signal of a photoluminescence emission mechanism |
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Lateral flow immunoassay (LFIA) | Optical properties |
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Chemiluminescence | Electrochemistry and visual luminescence measurements |
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Sardarabadi, P.; Kojabad, A.A.; Jafari, D.; Liu, C.-H. Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC). Biosensors 2021, 11, 394. https://doi.org/10.3390/bios11100394
Sardarabadi P, Kojabad AA, Jafari D, Liu C-H. Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC). Biosensors. 2021; 11(10):394. https://doi.org/10.3390/bios11100394
Chicago/Turabian StyleSardarabadi, Parvaneh, Amir Asri Kojabad, Davod Jafari, and Cheng-Hsien Liu. 2021. "Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)" Biosensors 11, no. 10: 394. https://doi.org/10.3390/bios11100394
APA StyleSardarabadi, P., Kojabad, A. A., Jafari, D., & Liu, C. -H. (2021). Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC). Biosensors, 11(10), 394. https://doi.org/10.3390/bios11100394