One-step multiplex analysis of breast cancer exosomes using an electrochemical strategy assisted by gold nanoparticles

Zhang, Mingwan; Xia, Lei; Mei, Wenjing; Zou, Qianli; Liu, Hui; Wang, Hongqiang; Zou, Liyuan; Wang, Qing; Yang, Xiaohai; Wang, Kemin

doi:10.1016/j.aca.2023.341130

Cited by 16 publications

(8 citation statements)

References 37 publications

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“…When compared to the standard qRT-PCR method used for the same miRNAs (ranging at ng/ml) ( 48 ), the sensitivities of the reported electrochemical multiplex assays were all notedly superior. The LOD of 10 3 –10 8 particles/ml for exosomal BC markers quantified by the electrochemical assay by Zhang and co-workers ( 45 ) can also be regarded as a great success when compared to detection by the tracking and analysis of nanoparticles (∼ 10 7 particles/ml) ( 49 ), flow cytometry, Western blotting and ELISA. However, the LOD declared for the e-multiplex sensors is comparable to other emerging breast cancer exosomal sensors measured by non-electrochemical methods such as colourimetry, fluorescence, surface-enhanced Raman scattering (15 particles/ul) ( 49 ), UV-Vis spectroscopy (LOD of 1.6 × 10 2 particles/μl) ( 50 ), and other optical methods.…”

Section: Discussionmentioning

confidence: 99%

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Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

O’Brien,

Khor,

Ardalan

et al. 2024

Front. Med. Technol.

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Herein, advancements in electroanalytical devices for the simultaneous detection of diverse breast cancer (BC) markers are demonstrated. This article identifies several important areas of exploration for electrochemical diagnostics and highlights important factors that are pivotal for the successful deployment of novel bioanalytical devices. We have highlighted that the limits of detection (LOD) reported for the multiplex electrochemical biosensor can surpass the sensitivity displayed by current clinical standards such as ELISA, FISH, and PCR. HER-2; a breast cancer marker characterised by increased metastatic potential, more aggressive development, and poor clinical outcomes; can be sensed with a LOD of 0.5 ng/ml using electrochemical multiplex platforms, which falls within the range of that measured by ELISA (from picogram/ml to nanogram/ml). Electrochemical multiplex biosensors are reported with detection limits of 0.53 ng/ml and 0.21 U/ml for MUC-1 and CA 15-3, respectively, or 5.8 × 10−3 U/ml for CA 15-3 alone. The sensitivity of electrochemical assays is improved when compared to conventional analysis of MUC-1 protein which is detected at 11–12 ng/ml, and ≤30 U/ml for CA 15-3 in the current clinical blood tests. The LOD for micro-ribonucleic acid (miRNA) biomarkers analyzed by electrochemical multiplex assays were all notedly superior at 9.79 × 10−16 M, 3.58 × 10−15 M, and 2.54 × 10−16 M for miRNA-155, miRNA-21, and miRNA-16, respectively. The dogma in miRNA testing is the qRT-PCR method, which reports ranges in the ng/ml level for the same miRNAs. Breast cancer exosomes, which are being explored as a new frontier of biosensing, have been detected electrochemically with an LOD of 103–108 particles/mL and can exceed detection limits seen by the tracking and analysis of nanoparticles (∼ 107 particles/ml), flow cytometry, Western blotting and ELISA, etc. A range of concentration at 78–5,000 pg/ml for RANKL and 16–1,000 pg/ml for TNF is reported for ELISA assay while LOD values of 2.6 and 3.0 pg/ml for RANKL and TNF, respectively, are demonstrated by the electrochemical dual immunoassay platform. Finally, EGFR and VEGF markers can be quantified at much lower concentrations (0.01 and 0.005 pg/ml for EGFR and VEGF, respectively) as compared to their ELISA assays (EGRF at 0.31–20 ng/ml and VEGF at 31.3–2,000 pg/ml). In this study we hope to answer several questions: (1) Are the limits of detection (LODs) reported for multiplex electrochemical biosensors of clinical relevance and how do they compare to well-established methods like ELISA, FISH, or PCR? (2) Can a single sensor electrode be used for the detection of multiple markers from one blood drop? (3) What mechanism of electrochemical biosensing is the most promising, and what technological advancements are needed to utilize these devices for multiplex POC detection? (4) Can nanotechnology advance the sensitive and selective diagnostics of multiple BC biomarkers? (5) Are there preferred receptors (antibody, nucleic acid or their combinations) and preferred biosensor designs (complementary methods, sandwich-type protocols, antibody/aptamer concept, label-free protocol)? (6) Why are we still without FDA-approved electrochemical multiplex devices for BC screening?

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Section: Discussionmentioning

confidence: 99%

“…The work completed by Zhang et al targets the release of HER2-positive breast cancer cell (SK-BR-3) exosomes via the use of a multiplex CD63, HER2, and EpCAM aptasensor ( 45 ). The authors looked to deposit aptamers on the electrode surface for specific binding to the exosomal cancer targets.…”

Section: Recent Progress: 2019–2023mentioning

confidence: 99%

Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

O’Brien,

Khor,

Ardalan

et al. 2024

Front. Med. Technol.

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“…Nanoparticles[ 22 ], nanotubes[ 14 ], nanowires[ 23 ], graphene[ 12 ] and other nanostructures can be integrated with sensor electrodes to enhance electron transfer, provide higher surface area, and incorporate catalytic properties. For instance, gold nanoparticles have been functionalized with aptamers for electrochemical detection of exosomes[ 24 ], which are emerging biomarkers for non-invasive cancer diagnosis. The high surface area of nanoparticles increases aptamer loading, allowing ultrasensitive exosome detection down to a few hundred particles per micro liter.…”

Section: Electrochemical Sensors Offer Advantages For Cancer Detectionmentioning

confidence: 99%

Leveraging electrochemical sensors to improve efficiency of cancer detection

Fu,

Karimi-Maleh

2024

World J Clin Oncol

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Electrochemical biosensors have emerged as a promising technology for cancer detection due to their high sensitivity, rapid response, low cost, and capability for non-invasive detection. Recent advances in nanomaterials like nanoparticles, graphene, and nanowires have enhanced sensor performance to allow for cancer biomarker detection, like circulating tumor cells, nucleic acids, proteins and metabolites, at ultra-low concentrations. However, several challenges need to be addressed before electrochemical biosensors can be clinically implemented. These include improving sensor selectivity in complex biological media, device miniaturization for implantable applications, integration with data analytics, handling biomarker variability, and navigating regulatory approval. This editorial critically examines the prospects of electrochemical biosensors for efficient, low-cost and minimally invasive cancer screening. We discuss recent developments in nanotechnology, microfabrication, electronics integration, multiplexing, and machine learning that can help realize the potential of these sensors. However, significant interdisciplinary efforts among researchers, clinicians, regulators and the healthcare industry are still needed to tackle limitations in selectivity, size constraints, data interpretation, biomarker validation, toxicity and commercial translation. With committed resources and pragmatic strategies, electrochemical biosensors could enable routine early cancer detection and dramatically reduce the global cancer burden.

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“…13 In particular, various aptasensors consisting of specific aptamers as the recognition element and signal transducer have gained great interest in the liquid biopsy field, especially for exosome detection. 14,15 Besides recognizing exosomes, the aptasensors can be combined with various signal transduction technologies including colorimetry, 16,17 electrochemistry, 18–20 electro-generated chemiluminescence, 21 fluorescence, 22–25 and Surface-Enhanced Raman Scattering (SERS) 26,27 to measure the concentration of the isolated exosomes. Among them, colorimetric aptasensors have been widely applied to detect exosomes due to their low cost, simplicity and observation with naked eyes, which is often based on natural peroxidases or peroxidase mimetics, such as horseradish peroxidase and carbon nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions

Zheng,

Huang,

Liu

et al. 2024

Anal. Methods

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One-step multiplex analysis of breast cancer exosomes using an electrochemical strategy assisted by gold nanoparticles

Cited by 16 publications

References 37 publications

Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

Leveraging electrochemical sensors to improve efficiency of cancer detection

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions

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