Progress in Tumor Biomarker Detection Based on Fluorescence Method

Biao Dong; Lihua Guo; Dayong Liu; Yuda Wang; Wei Liu; Rui Yang; Haitao He; Jiao Sun

doi:10.3788/CJL202249.2007103

Journals >Chinese Journal of Lasers >Volume 49 >Issue 20 >Page 2007103 > Article

Chinese Journal of Lasers
Vol. 49, Issue 20, 2007103 (2022)

Progress in Tumor Biomarker Detection Based on Fluorescence Method

Biao Dong¹, Lihua Guo¹, Dayong Liu¹, Yuda Wang², Wei Liu¹, Rui Yang¹, Haitao He², and Jiao Sun^2、*

Author Affiliations

¹State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, Jilin, China

²Department of Cell Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin, China

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DOI: 10.3788/CJL202249.2007103 Cite this Article Set citation alerts

Biao Dong, Lihua Guo, Dayong Liu, Yuda Wang, Wei Liu, Rui Yang, Haitao He, Jiao Sun. Progress in Tumor Biomarker Detection Based on Fluorescence Method[J]. Chinese Journal of Lasers, 2022, 49(20): 2007103 Copy Citation Text

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Fig. 1. Main types of tumor biomarkers^[4，10-14]

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Strategy of circulating tumor cell (CTC) capture and enrichment. (a) Interfacial viscoelastic microfluidics system based on CTC physical properties[88]; (b) microfluidic sorting platform for CTC based on multifunctional magnetic composites[87]; (c) in vivo identification of CTC by dual-targeting magnetic-fluorescent nanobeads[96]; (d) antibody-engineered red blood cell interface for high-performance capture and release of CTC[97]

Fig. 2. Strategy of circulating tumor cell (CTC) capture and enrichment. (a) Interfacial viscoelastic microfluidics system based on CTC physical properties^[88]; (b) microfluidic sorting platform for CTC based on multifunctional magnetic composites^[87]; (c) in vivo identification of CTC by dual-targeting magnetic-fluorescent nanobeads^[96]; (d) antibody-engineered red blood 　cell interface for high-performance capture and release of CTC^[97]

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Fig. 3. Follow-up detection of CTC. (a) Visible fluorescence detection of CTC by enzyme-free amplification based on CdTe quantum dots^[98]; (b) CTC detection based on CISe@ZnS NIR-Ⅱ luminescent nanoprobes^[89]

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Fig. 4. Direct detection of CTC. (a) Immunonanospheres-based one-step strategy for efficient detection of CTC^[104]; (b) direct detection strategy of CTC based on Ln^3＋ nanoprobes^[90]; (c) direct detection of CTC based on Au@CDs^[105]

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Fig. 5. Detection of ctDNA. (a) ctDNA detection based on integrated comprehensive droplet digital system^[114]; (b) ctDNA detection based on silicon nanowire array biosensor^[86]; (c) ctDNA detection based on upconversion nanoparticles^[117]

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Fig. 6. Detection of exosomes. (a) Detection of exosomes based on fluorescent biosensor^[126]; (b) detection of exosome based on fluorescent aptasensor^[129]; (c) detection of exosome surface proteins^[130]; (d) in situ measurement of exosomes^[131]; 　　(e) detection of exosomes based on microfluidic system^[133]

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Fig. 7. Detection of CEA. (a) Detection of CEA by fluorescencee-infrared absorption dual-mode nanoprobes^[135]; (b) rapid tumor screen strategy for CEA^[137]; (c) CEA detection in saliva samples^[136]

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Fig. 8. Detection of AFP. (a) AFP detection by fluorescence biosensor^[144]; (b) enzyme-free and dual-mode fluorescence detection of AFP^[151]; (c) enzyme-free detection of AFP based on aptamer^[146]

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Fig. 9. Detection of PSA. (a) Detection of PSA based on upconversion nanoparticles^[156]; (b) detecyion of PSA based on quantum dot^[155]; (c) detection of PSA based on molecularly-imprinted polymer^[157]

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Fig. 10. Multiple detection of tumor marker. (a) Detection of biomarker based on fluorescent material^[163]; (b) biomarker detection based on fluorescence resonance energy transfer system^[164]; (c) biomarker detection based on point-of-care testing^[168]

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Technology	Basic principle	Advantage	Disadvantage	Ref.
Radioimmunoassay	Radiolabelled antigen and radioactive measurement	Accurate and sensitive; reliable and applicable; easy operation；absolute quantification	Health hazards; radioactive contamination；limited stability	[15-16]
ELISA	Enzyme-labeled antigens or antibodies, enzyme-mediated visible color change or fluorescence to quantitative and qualitative measurements	Simplicity and scalability; ease operation; automated high-throughput; visual inspection; detection of a molecule at a low concentration	Time-consuming; high cost；moderate sensitivity；relatively complex strategy；specific equipment	[17-18]
Chemiluminescence immunoassay	Chemiluminescent substance labeled antigen or antibody，luminescence signal detection	High sensitivity and specificity；wide linear range; rapid and simple analysis; no scattered light interference	Weak signals and short luminescence time; limited precision for small molecules; matrix interference in complex samples	[19-20]
PCR	Enzymatic synthesis and amplification of specific DNA fragment; product analyze	High sensitivity; small amount of sample; multiplex; precise and accurate target quantification	Expensive with poor integration and multiplexing capability	[21-22]
Next-generation sequencing	Sequence millions of DNA molecule in one single run	Fast and efficient; high throughput; suitable for individual therapy of cancer	Expensive and mass processing of data; multiple steps of sample preparation; prone to mistakes	[23-24]
Mass spectrometry	Ionizing chemical species, separating and analyzing based on their mass-to-charge ratio	Rapid and sensitivity; high-throughput; structure identification; able to find new tumor biomarkers	Expensive equipment and complicated operation；invasive; low abundant proteins detection; prone to interference	[25-26]
SPR	Refractive index changes occurring from the capture of a molecule on the plasmonic surface	Label-free and real-time; high sensitivity and accuracy; suitable for a broad range of biofluids	Interference from complex samples; affects specificity and detection limits; most of them are in the proof-of-concept level	[27-29]
SERS	Difference in Raman scattering spectra of different molecule	Multiplexing capacity; high sensitivity and specificity; non-destructive and non-invasive	Expensive and expert-dependent equipment; batch to batch reproducibility of SERS substrates	[30-31]
Electrochemical sensors	Converts an interaction signal between a biometric element and a recognition target into a detectable electrical signal	High sensitivity; rapid and low cost; simple and suitable for microfabrication; mass production and integration	Lack of specificity for the captured cancer cells; lack the ability to detect intracellular protein markers	[32-33]
Flow cytometry	Measurement of cell size and cell granularity, expression of cell surface and intracellular molecules	Sorting capability; high-throughput measurement；rapidly counts	Indirect and in vitro measurement; time-consuming preparation	[34]
Fluorescence	Change of fluorescence spectrum and fluorescence intensity	High sensitivity and stability；simplicity and rapidity; biocompatibility; accurate data collection	Spectral overlap; background fluorescence; photobleaching; non-specific binding labeling	[35，31]

Table 1. Comparison of detection technique for tumor marker

Target	Material	Method	Linear range	Limits of detection	Time analysis	Sample	Ref.
CA19-9	QDs	Fluorescence quenching	2.76×10－2－5.23×102 U·mL－1	1.58×10－3 U·mL－1	21 min	Human serum	[68]
GPC3 or DKK1 or AFP	QDs	Fluorescent nanoprobes	0.625－2.5 ng·mL－1			Solution	[69]
CA125	UCNPs	Luminescence resonance energy transfer	0.01－100 U·mL－1	9.0×10－3 U·mL－1		Human serum	[70]
GPC-1	UCNPs	UCNPs-assisted single-molecule sandwich immunoassay	90－0.37 ng·mL－1	0.0123 ng·mL－1		Human serum	[71]
Leptin			100－0.412 ng·mL－1	0.2711 ng·mL－1
OPN			33.333－0.137 ng·mL－1	0.1238 ng·mL－1
VEGF			10－0.041 ng·mL－1	0.0158 ng·mL－1
Cyt c	CDs	Inner filter effect	0.5－25 μmol·L－1	0.25 μmol·L－1		Solution	[72]
HE4	CDs	Metal-enhanced fluorescence effect	0.01－200 nmol·L－1	2.3 pmol·L－1		Solution	[73]
Ovarian cancer cells	CDs	Metal-enhanced fluorescence effect	1.72×105－2.3×106 cell·mL－1	196 cell·mL－1		Solution	[73]
HE4	GQD	Ratiometric FRET	4.3 pmol·L－1－300 nmol·L－1	4.8 pmol·L－1		Solution	[74]
AFP	GQD	Electrochemical immunosensor	0.001－200 ng·mL－1	0.25 pg·mL－1		Solution	[75]
CEA or AFP	GO	Integrated microfluidic immunofluorescence micro assays chip	5 pg－0.5 mg	1 pg·mL－1	40 min	Human serum	[76]
CA199 or CA125 or CA153	GO		0.5－5000 U·mL－1	0.01 U·mL－1	40 min	Human serum	[76]
MMP-7	CNT	Electrochemical sensor and differential pulse voltammetry	0.01－1000 ng·mL－1	6 pg·mL－1	30 min	Solution Human serum; synthetic urine	[77]
MMP-7	CNT	Electrochemical sensor and differential pulse voltammetry	0－1000 ng·mL－1		30 min	Solution Human serum; synthetic urine	[77]
AKT2 gene	CNT	All-CNT thin-film transistor biosensors incorporated with tetrahedral DNA nanostructures	1 pmol·L－1－1 μmol·L－1	2 fmol·L－1		Solution	[78]
PSA	Pdots	FRET-based immunochromatographic strip	2－10 ng·mL－1	0.32 ng·mL－1	10 min	Whole blood	[79]
Exosomes	Pdots	Localized surface plasmon resonance	1.0×103－1.0×106 particle·mL－1	400 particle·mL－1		Solution	[80]
CEA	Pdots	Fluorometric immunochromatographic test strips	0－15 ng·mL－1	0.12 ng·mL－1	15 min	Solution	[81]
CYFRA 21-1	Pdots	Fluorometric immunochromatographic test strips	0－10 ng·mL－1	0.07 ng·mL－1	15 min	Solution	[81]
GSH	Metal nanoclusters	Fluorescence quenching interactions	0－1.75 μmol·L－1	0.1 μmol·L－1		Solution	[82]
MicroRNA-21	Metal nanoclusters	Paper colorimetric assay by nanocluster catalytic activity	1.0－700 pmol·L－1	0.6 pmol·L－1		Solution	[83]
MicroRNA-141	Metal nanoclusters	Entropy-driven amplification system and multiplexed analysis	0－50 nmol·L－1	6.1 pmol·L－1		Human serum	[84]
MicroRNA-155	Metal nanoclusters		0－50 nmol·L－1	8.7 pmol·L－1		Human serum	[84]
ACP	Fluorescent silicon Nanomaterials	Inner filtering effect	1.0－50 mU·L－1	0.3 mU·L－1	20 min	Human serum	[85]
PIK3CA E542K	Fluorescent silicon nanomaterials	SiNW array field effect transistor biosensor	0.1 fmol·L－1－100 pmol·L－1	10 amol·L－1		Solution Human serum	[86]
PIK3CA E542K	Fluorescent silicon nanomaterials	SiNW array field effect transistor biosensor	1 pmol·L－1－1 nmol·L－1	10 fmol·L－1		Solution Human serum	[86]

Table 2. Biomarkers detection based on fluorescent nanomaterial

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