Integrated SERS-Microfluidic Sensor Based on Nano-Micro Hierarchical Cactus-like Array Substrates for the Early Diagnosis of Prostate Cancer

Overview

Journal Biosensors (Basel)

Specialty Biotechnology

Date 2024 Dec 27

PMID 39727845

Authors

Huakun Jia

Weiyang Meng

Rongke Gao

Yeru Wang

Changbiao Zhan

Yiyue Yu

Haojie Cong

Liandong Yu

Affiliations

Soon will be listed here.

Abstract

The detection and analysis of cancer cell exosomes with high sensitivity and precision are pivotal for the early diagnosis and treatment strategies of prostate cancer. To this end, a microfluidic chip, equipped with a cactus-like array substrate (CAS) based on surface-enhanced Raman spectroscopy (SERS) was designed and fabricated for the detection of exosome concentrations in Lymph Node Carcinoma of the Prostate (LNCaP). Double layers of polystyrene (PS) microspheres were self-assembled onto a polyethylene terephthalate (PET) film to form an ordered cactus-like nanoarray for detection and analysis. By combining EpCAM aptamer-labeled SERS nanoprobes and a CD63 aptamer-labeled CAS, a 'sandwich' structure was formed and applied to the microfluidic chips, further enhancing the Raman scattering signal of Raman reporter molecules. The results indicate that the integrated microfluidic sensor exhibits a good linear response within the detection concentration range of 10 particles μL to 1 particle μL. The detection limit of exosomes in cancer cells can reach 1 particle μL. Therefore, we believed that the CAS integrated microfluidic sensor offers a superior solution for the early diagnosis and therapeutic intervention of prostate cancer.

References

van der Pol E, Coumans F, Grootemaat A, Gardiner C, Sargent I, Harrison P . Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost. 2014; 12(7):1182-92. DOI: 10.1111/jth.12602. View

Lin C, Liang S, Peng Y, Long L, Li Y, Huang Z . Visualized SERS Imaging of Single Molecule by Ag/Black Phosphorus Nanosheets. Nanomicro Lett. 2022; 14(1):75. PMC: 8922987. DOI: 10.1007/s40820-022-00803-x. View

An Y, Jin T, Zhu Y, Zhang F, He P . An ultrasensitive electrochemical aptasensor for the determination of tumor exosomes based on click chemistry. Biosens Bioelectron. 2019; 142:111503. DOI: 10.1016/j.bios.2019.111503. View

van der Pol E, Coumans F, Varga Z, Krumrey M, Nieuwland R . Innovation in detection of microparticles and exosomes. J Thromb Haemost. 2013; 11 Suppl 1:36-45. DOI: 10.1111/jth.12254. View

Kashefi-Kheyrabadi L, Kim J, Chakravarty S, Park S, Gwak H, Kim S . Detachable microfluidic device implemented with electrochemical aptasensor (DeMEA) for sequential analysis of cancerous exosomes. Biosens Bioelectron. 2020; 169:112622. DOI: 10.1016/j.bios.2020.112622. View

Chung E, Gao R, Ko J, Choi N, Lim D, Lee E . Trace analysis of mercury(II) ions using aptamer-modified Au/Ag core-shell nanoparticles and SERS spectroscopy in a microdroplet channel. Lab Chip. 2012; 13(2):260-6. DOI: 10.1039/c2lc41079f. View

Sokolova V, Ludwig A, Hornung S, Rotan O, Horn P, Epple M . Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces. 2011; 87(1):146-50. DOI: 10.1016/j.colsurfb.2011.05.013. View

Shin H, Oh S, Hong S, Kang M, Kang D, Ji Y . Early-Stage Lung Cancer Diagnosis by Deep Learning-Based Spectroscopic Analysis of Circulating Exosomes. ACS Nano. 2020; 14(5):5435-5444. DOI: 10.1021/acsnano.9b09119. View

Crocetto F, Russo G, Di Zazzo E, Pisapia P, Mirto B, Palmieri A . Liquid Biopsy in Prostate Cancer Management-Current Challenges and Future Perspectives. Cancers (Basel). 2022; 14(13). PMC: 9265840. DOI: 10.3390/cancers14133272. View

10.

Wang B, Duan G, Xu W, Xu C, Jiang J, Yang Z . Flexible surface-enhanced Raman scatting substrates: recent advances in their principles, design strategies, diversified material selections and applications. Crit Rev Food Sci Nutr. 2022; 64(2):472-516. DOI: 10.1080/10408398.2022.2106547. View

11.

Zhang Y, Liu Y, Liu H, Tang W . Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019; 9:19. PMC: 6377728. DOI: 10.1186/s13578-019-0282-2. View

12.

Zhao Q, Cheng X, Hu S, Zhao M, Chen J, Mu M . Bilateral efforts to improve SERS detection efficiency of exosomes by Au/NaPMoO Combined with Phospholipid Epitope Imprinting. Biosens Bioelectron. 2024; 258:116349. DOI: 10.1016/j.bios.2024.116349. View

13.

Kwizera E, OConnor R, Vinduska V, Williams M, Butch E, Snyder S . Molecular Detection and Analysis of Exosomes Using Surface-Enhanced Raman Scattering Gold Nanorods and a Miniaturized Device. Theranostics. 2018; 8(10):2722-2738. PMC: 5957005. DOI: 10.7150/thno.21358. View

14.

Hao N, Pei Z, Liu P, Bachman H, Naquin T, Zhang P . Acoustofluidics-Assisted Fluorescence-SERS Bimodal Biosensors. Small. 2020; 16(48):e2005179. PMC: 7902458. DOI: 10.1002/smll.202005179. View

15.

Ruan S, Wang W, Qiu L, Yan X, Peng Z, Zhu H . Preparation of 3D flexible SERS substrates by mixing gold nanorods in hydrogels for the detection of malachite green and crystal violet. Mikrochim Acta. 2024; 191(4):205. DOI: 10.1007/s00604-024-06284-6. View

16.

Gao R, Lv Z, Mao Y, Yu L, Bi X, Xu S . SERS-Based Pump-Free Microfluidic Chip for Highly Sensitive Immunoassay of Prostate-Specific Antigen Biomarkers. ACS Sens. 2019; 4(4):938-943. DOI: 10.1021/acssensors.9b00039. View

17.

Zhao L, Wang H, Fu J, Wu X, Liang X, Liu X . Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron. 2022; 214:114487. DOI: 10.1016/j.bios.2022.114487. View

18.

Nguyen T, Jeong S, Kang S, Han S, Nguyen T, Lee S . 3D Superclusters with Hybrid Bioinks for Early Detection in Breast Cancer. ACS Sens. 2024; 9(2):699-707. PMC: 10897927. DOI: 10.1021/acssensors.3c01938. View

19.

Li C, Guo L, Sang X, Jiang X, Wang H, Qin P . Colorimetric aptasensor based on spherical nucleic acid-induced hybridization chain reaction for sensitive detection of exosomes. Talanta. 2023; 258:124453. DOI: 10.1016/j.talanta.2023.124453. View

20.

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R . Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024; 4(1):47-53. PMC: 11256708. DOI: 10.1016/j.jncc.2024.01.006. View