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Recent advancements in electrochemical transducer based integrated microfluidic devices for breast cancer specific biomarker detection. (I) Detailed steps involved during the construction of the mFED device for estrogen receptor alpha (ERa) detection. Reproduced with permission. 104 Copyright 2018, Elsevier. (II) Electrochemical fully inkjet printed array for sandwich immunoassay-based detection of HER2. Reproduced with permission. 105 Copyright 2018, Elsevier. (III) Capacitive electrochemical device for the detection of HER2. Reproduced with permission. 106 Copyright 2018, Elsevier.
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Timely and accurate diagnosis of breast cancer is essential for efficient treatment and the best possible survival rates. Biosensors have emerged as a smart diagnostic platform for the detection of biomarkers specific to the onset, recurrence, and therapeutic drug monitoring of breast cancer. There have been exciting recent developments, including...
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... proposed mFED was fabricated by sandwiching two polystyrene sheets with screen-printed counter electrodes (CEs), reference electrodes (REs), and a microarray of 8 working electrodes (WEs) using adhesive polystyrene cards (Fig. 5I). The surface of the WEs was modied with estrogen response elements (DNA-ERE) to bind target ERa. However, to ensure an amplied electrochemical response, the target ERa was magnetically enriched using anti ERa, and a HRP labeled magnetic particle bioconjugate (MP-Ab-HRP). The resulting bioconjugate was further introduced into the ...
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... the clinical utility of POC devices towards HER2. 105 The proposed device included an electrochemical platform with eight inkjet-printed gold electrode arrays (WEA)s, a CE, and an Ag/AgCl electrode. The device was designed to implement a sandwich immunoassay in the presence of the target analyte, biotin functionalized antibody, and HRP labels (Fig. 5II). The low-cost device (0.25 $) exhibited a quick response (assay time: 15 min) and a DL of 12 pg mL À1 towards HER2. Moreover, the device's analytical performance was reproducible, sensitive, and stable, with standard recoveries ranging from 76% to 103%. Later, the potential of the DNA aptasensor (fabricated through the immobilization ...
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... min) and a DL of 12 pg mL À1 towards HER2. Moreover, the device's analytical performance was reproducible, sensitive, and stable, with standard recoveries ranging from 76% to 103%. Later, the potential of the DNA aptasensor (fabricated through the immobilization of a thiolated HER2 specic aptamer on gold interdigitated microelectrodes (IDmEs)) (Fig. 5III) was combined with capacitive measurements to improvise the analytical response of the biosensor towards HER2. 106 The proposed non-faradaic mode of impedance spectroscopy predominantly relied on the charging currents (rather than faradaic current arising from the oxidation/reduction of the redox couple (Fe 2+ /Fe 3+ )) originating from ...
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Citations
... [2,[7][8][9][10] Moreover, the cost-effectiveness, minimal clinical specimen requirements, miniaturization, simple operation, and user-friendliness enhance their immunosensing applicability. [7,[11][12][13] To fabricate an electrochemical immunosensor, functional, conductive, and high surface-containing materials have been required. Since the functional group and high surface area improve the immobilization of antibodies against target antigen. ...
Early diagnosis of cancer can be achieved by detecting associated biomarkers before the appearance of symptoms. Herein, we have developed an electrochemical immunosensor of ionic liquid tailored to molybdenum trioxide‐reduced graphene oxide (MoO3‐rGO‐IL) nanocomposite to detect carcinoembryonic antigen (CEA), a cancer biomarker. The MoO3‐rGO‐IL nanocomposite has been synthesized in situ via the hydrothermal method. The functionalization of 1‐butyl‐3‐methylimidazolium tetrafluoroborate IL with MoO3‐rGO synergistically improves the electrochemical and surface properties of the nanocomposite. The characterization studies revealed that the MoO3‐rGO‐IL nanocomposite is a highly appropriate material for the construction of immunosensors. The material exhibits exceptional electrical conductivity, surface properties, stability, and a large electrochemical effective surface area (13.77×10⁻² cm²) making it ideal for fabricating immunosensors. The quantitative outcome showed that the developed immunosensor (BSA/anti‐CEA/MoO3‐rGO‐IL/GCE) possesses excellent sensitivity, broad linearity from 25 fg mL⁻¹ to 100 ng mL⁻¹, and a low detection limit of 1.19 fg mL⁻¹. Moreover, the remarkable selectivity, repeatability, and efficiency of detecting CEA in serum specimens demonstrated the feasibility of the immunosensor. Thus, the projected electrochemical immunosensor can potentially be utilized for the quantification of CEA in clinical specimens.
... In recent years, several reviews of different biosensors, particularly electrochemical biosensors for early detection of different cancers (especially breast cancer), as well as various biomarkers have been conducted [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]; however, due to the high importance of this subject area, there is a need for these types of studies to be updated annually. In this review, some designed or developed electrochemical biosensors and the methods and strategies of fabricating these types of sensors for the early detection of breast cancer are reviewed, and the limitations and challenges of these investigations as well as the obstacles in their commercialization are investigated. ...
... In addition, under experimental advances like enhanced fabrication techniques( such as nanosphere lithography, electron beam lithography, and nanoimprint lithography) and improved surface functionalization, have been developed considering temperature dependence coating to enable better reproducibility and scalability in biosensor fabrication 23 . Temperature dependence of the coating affects the sensor's response by improving refractive index, signal stability, and establish proper calibration and normalization 55,56 . Further, some computational advances are: high-performance computing, machine learning and data analytics have been applied to handle the large datasets generated by plasmonic biosensors. ...
Cancer causes one in six deaths worldwide, and 1.6 million cancer patients face annual out-of-pocket medical expenditures. In response to these, portable, label-free, highly sensitive, specific, and responsive optical biosensors are under development. Therefore, in this review, the recent advances, advantages, performance analysis, and current challenges associated with the fabrication of plasmonic biosensors, photonic crystals, and the hybridization of both for cancer diagnosis are assessed. The primary focus is on the development of biosensors that combine different shapes, sizes, and optical properties of metallic and dielectric nanoparticles with various coupling techniques. The latter part discusses the challenges and prospects of developing effective biosensors for early cancer diagnosis using dielectric and metallic nanoparticles. These data will help the audience advance research and development of next-generation plasmonic biosensors for effective cancer diagnosis.
... Two major requirements of PEDBCB detecting POCD eligible to be commercialized faces some of the major challenges such as (i) target biomarkers validation, (ii) large sample volume validation, (iii) ultrasensitivity and specificity which is clinically reliable, (iv) sample processing, purification, and amplification duration and protocol, (v) affordability for varied categories of users, (vi) automated analytical procedures, (vii) user-friendly signal readout and ensured reliable detection and (viii) efficient power or storage sources (Gootenberg et al., 2017;Joshi et al., 2021). The CRISPR/Cas diagnostic platforms eventhough is booming with extraordinary sensing efficacy in early BC diagnostics, it still lacks in (i) target amplification procedures, (ii) short shelf life, (iii) nanomaterial degradation in some of the biospecimens, and (iv) design complexities. ...
... They are a cost-effective alternative to traditional diagnostic techniques and are suitable for use in a range of settings, which make them a preferred tool for BC screening programs. The main objective of ongoing research in this field is to enhance the reliability and sensitivity of these sensors, making them a viable and trustworthy technique in BC detection and monitoring [14][15][16]. Nanomaterials are one strategy for improving the feasibility of sensors used in BC diagnosis. They improve sensor sensitivity and specificity, thereby increasing their efficiency in detecting BC biomarkers. ...
A screen-printed carbon electrode was used to develop a biosensor with an improved response and selectivity for detecting human epidermal growth factor receptor 2 (HER2). To investigate the performance of the biosensor, electrochemical characterizations such as impedance spectroscopy, differential pulse and cyclic voltammetry were used, in addition to Fourier transform infrared spectroscopy and atomic force microscopy. The biosensor responds in a quick manner, taking only 5 minutes to bind to the target protein. Furthermore, the results show that the nano-biosensor has a detection limit of 4.4 Pg/ml. The findings suggest that the biosensor can be used as a potential analytical tool for HER2 detection, particularly at low concentrations, which can be a tool used in the early detection of breast cancer.
... The fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) 17 , and immunohistochemical methods are conventional diagnosis assays for HER-2 determination. Due to some restrictions such as the lack of sensitivity, timeconsumption, complexity, and expensiveness in mentioned methods, alternative technologies have been widely studied to more sensitively and effectively detect the HER-2 biomarker 18,19 . These include electrochemical 20-25 , optical 26-31 and piezoelectric biosensors 32,33 . ...
Breast cancer (BC) is one of the most commonly diagnosed cancers and the second leading cause of cancer mortality among women around the world. The purpose of this study is to present a non-labeled liquid crystal (LC) biosensor, based on the inherent feature of nematic LCs, for the evaluation of BC using the human epidermal growth factor receptor-2 (HER-2) biomarker. The mechanism of this sensing is supported by surface modification with dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) encouraging the long alkyl chains that induce a homeotropic orientation of the LC molecules at the interface. To enhance the binding efficacy of more HER-2 antibody (Ab) on LC aligning agents, a simple ultraviolet radiation-assisted method was also used to increase functional groups on the DMOAP coated slides, thereby improving binding affinity and efficiency onto HER-2 Abs. The designed biosensor makes use of the specific binding of HER-2 protein to HER-2 Ab and disruption of the orientation of LCs. This orientation change leads to a transition of the optical appearance from dark to birefringent, enabling the detection of HER-2. This novel biosensor exhibits a linear optical response to HER-2 concentration in the wide dynamic range of 10–6–10² ng/mL, with an ultra-low detection limit of 1 fg/mL. As a proof of concept, the designed LC biosensor was successfully investigated for the quantification of HER-2 protein in patients suffering from BC. Owing to the sensitivity, selectivity, and label-free detection, this biosensor may amplify the application of LC-based biosensors for the detection of most types of cancers.
... Nowadays, point-of-care biosensors are one of the most emerging recognition technologies for the detection of biomarkers [6]. The ability of point-of-care and ultimately reducing the cost of treatments are the most important aspects of biosensors which is considered recently [7]. ...
Developing smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor. Accordingly, commercial polyurethane (PU) foam was first coated with graphene oxide (GO) to increase its surface area (8.45-fold), and improve its wettability. The surface of the resulting three-dimensional PU-GO (3DPU-GO) platform was then modified by MUC1 aptamer-GNCs to provide the required sensitivity and specificity through a turn "on/off" detection system. The proposed biosensor was first optimized with a spectrophotometer method. Afterward, findings were evaluated based on the red color intensity of the lab-in-a-tube system; and indicated the high ability of the biosensor for detection of MUC1-overexpressed tumor cell lines in the range of 250-20,000 cells mL-1 with a limit of detection of 221 cells mL-1. In addition, the developed biosensor showed a decent selectivity against positive-control cell lines (MCF-7, and HT-29) in comparison to negative-control cell lines (HEK293, and L929). Notably, the results represented good accordance with reference methods including spectroscopy devices. Ultimately, the results of this work bring a new perspective to the field of point-of-care detection and can be considered in future biosensors.
... 11 Numerous sensor platforms, exclusively the electrochemical biosensors utilizing enzyme-modified, DNAs immobilized, aptamers based, nanomaterials and composites modifed, etc. have become an evolving alternative method due to their easy operating nature, on-site detection possibility, affordable instrumentation, smallness, and its robustness of developing point-of-care screening and diagnostic devices for the detection of BC biomarkers. [12][13][14][15][16][17][18][19][20] Nonetheless, the electrochemical detection of MCs which is composed of calcium oxalate and hydroxyapatite cannot be a direct reliable diagnosis. Hence, to achieve sensitivity, specificity, improved test efficiency, shortened analytical time, decreased sampling volume, reduced cost and reliable diagnostic results it is highly preferable to quantify and determine the potential biomarkers responsible for the DCIS condition via liquid biopsy. ...
... 21 Nevertheless, most of the reports have been focussed on the BC biomarkers which have been recognized as metastatic BC biomarkers, which are found at stages I-IV. [12][13][14][15][16][17][18][19][20] Tumor Markers (EGTM) and the American Society of Clinical Oncology (ASCO) guidelines for BC screening even though approved by FDA due sensitivity issues and the lacking confirmation for their significance in early-stage BC control. 22 Other significant DCIS biomarkers include microribonucleic acids (miRNAs), lipids, and the proteins p16, COX-2, Ki67, in addition to HER-2, estrogen and progesterone. ...
Till date, no systematic review is conducted on electrochemical biosensing of multiplexed breast cancer miRNAs to identify their suitability as an alternative diagnostic tool for ductal carcinoma in-situ (DCIS). Original articles published in English from PUBMED, Science Direct, Scopus, MEDLINE, Cochrane Library, National Centre for Biotechnology Information, and Google scholar during Jan 2012– Feb 2022 were searched using set inclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines was followed to report this review. Methodological quality of the included studies was evaluated using Risk of Bias (ROB) assessment criteria. Out of 1973 screened articles, 17 studies were eligible and included in this review wherein, 1 study (5.88%) involving generic neutravidin modified nanolabel probe using biotintylated molecular beacons immobilized metal nanoparticles prepared using one pot assay to detect miRNAs 21 and 141 had low ROB and 16 studies (94.12%) had medium ROB. Medium ROB of majority of the included studies reveals its limited evidence to conclude its suitability for diagnosing DCIS using miRNAs. High quality studies with inter assays and validation are extensively needed for the development of diagnostic tool for DCIS via miRNAs.
... Since the NIR light permeation through the biological tissues is far greater than the visible radiation, the excitation and emission spectra in the NIR range in UCNPs are useful in deep tissue imaging [69]. Also, UCNPs have been found to have applications in optical tracking [70], molecular biosensing [71], temperature and pH sensing [72], small molecule (nucleic acid)/electrolyte/heavy metal identification [73][74][75] and Point-of-care diagnostics [76,77]. In the field of nanomedicine, UCNPs have found applications in light-induced chemotherapy and gene therapy [78], photodynamic therapy [79], photothermal therapy [80] and immunotherapy [81], and Optogenetics and neural manipulation [82,83]. ...
Hybrid nanostructures are nanocomposites constructed from at least two different types of materials to imbibe the individual advantages while overcoming individual shortcomings and forming one nanostructure with superior properties not possessed by single component nanostructures. Organic and inorganic hybrid nanostructures are a class of promising nanocomposites that possess interesting biological and physicochemical properties, making them highly attractive in biomedical applications. Recently, organic hybrid nanostructures such as hybrid lipid-based systems, hybrid polymeric nanoparticles, micelles, dendrimers and inorganic hybrid nanostructures such as metal nanoparticles, hybrid carbon nanomaterials, hollow mesoporous silica nanoparticles, hybrid magnetic nanoparticles and layered double hydroxides nanosheets and organic–inorganic hybrid nanostructures are developed for implementation in nanomedicine. Numerous studies have been conducted to investigate the employment of hybrid nanostructures in biomedical fields for gene therapy, chemotherapy, immunotherapy, combination chemotherapy, imaging platform, photodynamic and photothermal therapy. Novel hybrid nanostructures with multi-functional features have been evolved. This review summarizes the recent development and applications and directs the future perspective of hybrid nanostructures in biomedical applications.
... First, we analyzed the effects induced in the TFBGs transmitted amplitude spectrum for SRI changes in the range 1.3360-1.3370. Then, we biofunctionalized the gold film with single-strand DNA aptamers as bioreceptors to turn the platform into a biosensor [28][29][30]. We have been able to assess the sensing performances of this TFBG platform for human epidermal growth factor receptor (HER2) protein, a relevant cancer biomarker [31,32]. ...
To date, there is clear experimental evidence that gold-coated tilted fiber Bragg gratings (TFBGs) are highly sensitive plasmonic biosensors that provide temperature-compensated detection of analytes at concentrations in the picomolar range. As most optical biosensors, they bring an evanescent wave in the surrounding medium, which makes them sensitive to both surface refractive index variations (= the useful biosensing signal) and to bulk refractive index changes (= the non-useful signal for biosensing). This dual sensitivity makes them prone to drift. In this work, we study partially gold-coated TFBGs around their cross-section. These gratings present the ability to discriminate both volume and surface refractive index changes, which is interesting in biosensing to enhance the signal-to-noise ratio. The effects induced in the TFBGs transmitted amplitude spectra were analyzed for surrounding refractive index (SRI) changes in the range 1.3360–1.3370. Then, the gold film was biofunctionalized with human epidermal growth factor receptor (HER2) aptamers using thiol chemistry. The detection of HER2 proteins (a relevant cancer biomarker) at 10⁻⁹ g/mL, 10⁻⁸ g/mL and 10⁻⁶ g/mL demonstrated the advantage to identify environmental perturbations through the bare area of the TFBGs, which is left not functionalized. The non-specific drifts that could exist in samples are eliminated and a wavelength shift only related to the surface modification is obtained.
