A filter-electrochemical microfluidic chip for multiple surface protein analysis of exosomes to detect and classify breast cancer

Wang, Yanlin; Gao, Wenjing; Sun, Min; Feng, Bin; Shen, Hao; Zhu, Jing; Chen, Xueqin; Yu, Shaoning

doi:10.1016/j.bios.2023.115590

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…The development of micro- and nano-biosensors gives us a unique lens into the possible future of cancer screening, diagnostics, and in-real-time treatment management. For instance, in microfluidic devices can take small quantities of human serum and pump them through a small array of tubes ( 53 ). As the serum passes over the electrode surface, and the target analyte comes into contact with biorecognition molecules which had been deposited on the electrode surface, we can all but guarantee that binding will occur due to the repetitive flow of the serum over the biorecognition element.…”

Section: Discussionmentioning

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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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%

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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“…To date, great efforts have been devoted to introducing various signal production and amplification strategies, such as metal nanoparticles, tetrahedral DNA nanostructures (TDNs), and nucleic acid-based amplification analysis, to electrochemical biosensors for EV detection. For example, Wang et al have developed a new filter electrochemical microfluidic chip (FEMC) that integrates on-chip separation and in situ surface protein electrochemical analysis of exosomes in the whole blood of breast cancer patients [80]. In this system, zirconium-based metal-organic frameworks (Zr-MOFs) loaded with numerous electroactive methylene blue molecules (Zr-MOFMB@UiO-66) were attached to exosomes collected on electrode surfaces, leading to the amplification of electrical signals.…”

Section: Electrochemical Detectionmentioning

confidence: 99%

Recent Advances in Microfluidic-Based Extracellular Vesicle Analysis

Chen,

Zheng,

Xiao

et al. 2024

Micromachines

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Extracellular vesicles (EVs) serve as vital messengers, facilitating communication between cells, and exhibit tremendous potential in the diagnosis and treatment of diseases. However, conventional EV isolation methods are labor-intensive, and they harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as the limited sensitivity and specificity of traditional EV analysis methods, hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, and low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the distinct advantages of microfluidic technology in enhancing the capture efficiency and precise targeting of extracellular vesicles (EVs). We also explore its analytical role in targeted detection. Furthermore, this review highlights the transformative impact of microfluidic technology on EV analysis, with the potential to achieve automated and high-throughput EV detection in clinical samples.

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“…Various analytical methods have been developed to overcome these limitations, including fluorescence, [23][24][25] electrochemical, 26,27 surface-enhanced Raman spectroscopy (SERS), 28,29 electrochemiluminescence, [30][31][32] chemiluminescence, 33 photoelectrochemical biosensing assays (PEC), 34,35 and colorimetric assays. 36,37 These methods not only enhance the sensitivity of DNMT detection, are easy to operate, and are low cost, but also provide certain advantages in the detection of other molecular biomarkers in the biological field, such as exosomes, [38][39][40] nucleic acids, [41][42][43] proteins, 44,45 antibodies, 46,47 cells, 48,49 enzymes, 50,51 and other important biological target assays.…”

Section: Introductionmentioning

confidence: 99%

Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays

Huang,

Zhao,

et al. 2024

J. Mater. Chem. B

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A filter-electrochemical microfluidic chip for multiple surface protein analysis of exosomes to detect and classify breast cancer

Cited by 8 publications

References 30 publications

Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers

Recent Advances in Microfluidic-Based Extracellular Vesicle Analysis

Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays

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