Graphene quantum dot–based electrochemical biosensing for early cancer detection

Electrochemical biosensing systems coupled with graphene quantum dots (GQDs) have demonstrated suitability for cancer diagnostic strategies, particularly to identify the changes facilitating the early phases of tumorigenesis as well as to detect ultralow concentrations of biomarkers that distinguish between normal and malignant cells. GQDs, known as a novel class of zero-dimensional semiconductor nanocrystals, are tiny graphene particles arranged in a honeycomb structure with a size range of 1–50 nm. The size of these GQDs is comparable with the size of biomolecules, thereby providing an ideal platform to study biomolecules such as proteins, cells, and viruses. GQDs are a superior platform for specific and sensitive recognition of cancer biomarkers; they are highly synergistic with electrochemical sensors. This review will shed light on the recent advancements made in the field of GQD-based electrochemical sensors for early cancer detection, with the aim of highlighting the prospects for further development in cancer diagnostics.     

Advanced electrocatalytic materials based biosensors for cancer cell detection – A review

Herein, we have highlighted the latest developments on biosensors for cancer cell detection. Electrochemical (EC) biosensors offer several advantages such as high sensitivity, selectivity, rapid analysis, portability, low-cost, etc. Generally, biosensors could be classified into other basic categories such as immunosensors, aptasensors, cytosensors, electrochemiluminescence (ECL), and photo-electrochemical (PEC) sensors. The significance of the EC biosensors is that they could detect several biomolecules in human body including cholesterol, glucose, lactate, uric acid, DNA, blood ketones, hemoglobin, and others. Recently, various EC biosensors have been developed by using electrocatalytic materials such as silver sulfide (Ag₂S), black phosphene (BPene), hexagonal carbon nitrogen tube (HCNT), carbon dots (CDs)/cobalt oxy-hydroxide (CoOOH), cuprous oxide (Cu₂O), polymer dots (PDs), manganese oxide (MnO₂), graphene derivatives, and gold nanoparticles (Au-NPs). In some cases, these newly developed biosensors could be able to detect cancer cells with a limit of detection (LOD) of 1 cell/mL. In addition, many remaining challenges have to be addressed and validated by testing more real samples and confirm that these EC biosensors are more accurate and reliable to measure cancer cells in the blood and salivary samples.     

CuS–MWCNT based electrochemical sensor for sensitive detection of bisphenol A

The rapid and simple detection of bisphenol A is very important for the safety and reproduction of organisms. Here, a sensitive and reliable electrochemical sensor was established for bisphenol A detection based on the high amplification effect of copper sulfide-multi-walled carbon nanotube (CuS–MWCNT) nanocomposites. The flower-like CuS–MWCNT were successfully synthesized by a simple hydrothermal method accompanied by polyvinylpyrrolidone (PVP). Compared with bare glassy carbon electrode (GCE), CuS–MWCNT modified GCE could amplify the electrochemical signals in about ten times, which was attributed to the synergistic effect of CuS and MWCNT. The MWCNT could increase the specific surface area of electrodes and improve the electrode activity. The integration of CuS could further enhance the electrode conductivity as well as accelerate the electron transfer rate. Raman spectra and transmission electron microscope (TEM) were used to characterize the successful fabrication of CuS–MWCNT nanocomposites and its uniform and monodispersed morphology. Under optimizing conditions, the oxidation currents of bisphenol A via the differential pulse voltammetric (DPV) showed a good linear relationship with its concentration in a wide range of 0.5–100 μM, with a detection limit of 50 nM. This electrochemical sensor of bisphenol A provided a convenient and economical platform with high sensitivity and reproducibility, which had great potential in environmental monitoring.     

Cerium oxide nanofiber–based electrochemical immunosensor for detection of sepsis in biological fluid

Sepsis causes life-threatening complications with the highest burden of death and medical expenses in hospitals worldwide. Despite the progression of targeted therapies for sepsis, the challenge of early diagnosis of sepsis-related biomarkers remains. The analysis of the TNF-α and sTREM-1 in biological fluids provides essential information for effective treatments. In this work, we report developing an electrochemical immunosensor for the rapid detection of TNF-α and sTREM-1 proteins in human plasma samples. First, using the electrospinning process, cerium oxide nanofibers were synthesized. Subsequently, the antibodies corresponding to the targeted proteins are immobilized onto the surface-functionalized working electrodes using NHS/EDC chemistry. The proposed immunosensor’s performance in a biological fluid was assessed using an analytical electrochemistry approach. The limit of detection for the electrochemical immunosensors was 0.51 and 0.41 pg/mL for TNF-α and sTREM-1, respectively, with high selectivity and sensitivity for the use as a point of care device.

     

A ratiometric electrochemical biosensor for sensitive detection of Hg based on thymine–Hg–thymine structure

In this paper, a simple, selective and reusable electrochemical biosensor for the sensitive detection of mercury ions (Hg²⁺) has been developed based on thymine (T)-rich stem–loop (hairpin) DNA probe and a dual-signaling electrochemical ratiometric strategy. The assay strategy includes both “signal-on” and “signal-off” elements. The thiolated methylene blue (MB)-modified T-rich hairpin DNA capture probe (MB-P) firstly self-assembled on the gold electrode surface via Au–S bond. In the presence of Hg²⁺, the ferrocene (Fc)-labeled T-rich DNA probe (Fc-P) hybridized with MB-P via the Hg²⁺-mediated coordination of T–Hg²⁺–T base pairs. As a result, the hairpin MB-P was opened, the MB tags were away from the gold electrode surface and the Fc tags closed to the gold electrode surface. These conformation changes led to the decrease of the oxidation peak current of MB (I_MB), accompanied with the increase of that of Fc (I_Fc). The logarithmic value of I_Fc/I_MB is linear with the logarithm of Hg²⁺ concentration in the range from 0.5 nM to 5000 nM, and the detection limit of 0.08 nM is much lower than 10 nM (the US Environmental Protection Agency (EPA) limit of Hg²⁺ in drinking water). What is more, the developed DNA-based electrochemical biosensor could be regenerated by adding cysteine and Mg²⁺. This strategy provides a simple and rapid approach for the detection of Hg²⁺, and has promising application in the detection of Hg²⁺ in real environmental samples.     

Graphene–Au composite sensor for electrochemical detection of para-nitrophenol

A novel electrochemical sensor for para-nitrophenol (p-NP) was constructed with graphene–Au composite containing 10 % Au (G–Au 10 %). In the composite, Au nanoparticles with the size of ca. 11 nm were regularly scattered on graphene sheet without aggregation, which offers dramatically higher electrocatalytic activity on the redox of K₃[Fe(CN)₆]/K₄[Fe(CN)₆] couple than sole Au nanoparticles. Compared to sole Au nanoparticles, the G–Au 10 % also exhibited dramatically improved electrocatalytic activity on the reduction of p-NP. Amperometric detection of p-NP at G–Au 10 % modified electrode displayed a wide linear range of 0.47–10.75 mM with detection limit of 0.47 μM and a high sensitivity of 52.85 μA/mM. Considering the thrifty in utilization of noble Au, the G–Au 10 % can be successfully applied as a low-cost and powerful sensing material for trace detection of p-NP.     

Direct electrochemical sensing of ο-phenylendiamine based on perovskite-type nanomaterial LaNiTiO3–Fe3O4

An electrochemical sensor is developed in this work based on the new perovskite-type nanomaterial LaNiTiO₃–Fe₃O₄ for sensitive determination of o-phenylenediamine (OPD). As-synthesized materials and the surface of as-fabricated electrochemical sensor are characterized by X-ray diffraction, atomic force microscope, and electrochemical impedance spectroscopy, respectively. The results of characterizations depict that the sample is of nanoscaled complex oxides consisting of perovskite structure and spinel structure, and has good conductive properties. The construction and experimental conditions of the electrochemical sensor are also optimized. The electrochemical properties of OPD at glassy carbon electrode modified with LaNiTiO₃–Fe₃O₄ are investigated in alkaline solution (NaOH). The new electrochemical sensor exhibits high electrocatalytic activity and stability in NaOH, and a promotion of electrochemical oxidation of OPD at low potentials can be obviously observed. A wide linear range is obtained from 1.0?×?10^?6 to 7.0?×?10^?3 M with a relative low detection limit of 0.15 μM (S/N?=?3) under optimal conditions. Furthermore, the sensor exhibits reliable results for the determination of OPD in commercial samples.     

Recent progress in the design of G-quadruplex–based electrochemical aptasensors

Aptamer-based electrochemical sensors are now developed for the detection of a wide variety of analytes including ions, low-molecular-weight molecules, proteins, and living cells. An aptamer-based sensor is an analytical device whose bio-sensing element (i.e. the aptamer) is immobilized on a transducer surface. Aptasensors have attracted great attention because of their high selectivity, sensitivity, and stability; they could be miniaturized and are of low production cost and offer extraordinary flexibility in the design of their assemblies. This review will emphasize recent developments of aptasensors using aptamers that are able to adopt the particular G-quadruplex (G4) conformations, which are secondary DNA structures formed from guanine-rich sequences. Indeed, G4 exhibits notable recognition properties inherent to their particular structuration.     

An electrochemical signal switch–based (on–off) aptasensor for sensitive detection of insulin on gold-deposited screen-printed electrodes

Journal of Solid State Electrochemistry - Insulin hormone is of great importance for many diseases, especially for diabetes management. Therefore, different detection strategies have been used for...     

An electrochemical biosensor based on DNA “nano-bridge” for amplified detection of exosomal microRNAs

Exosomal miRNAs, as potential biomarkers in liquid biopsy for cancer early diagnosis, have aroused widespread concern. Herein, an electrochemical biosensor based on DNA “nano-bridge” was designed and applied to detect exosomal microRNA-21 (miR-21) derived from breast cancer cells. In brief, the target miR-21 can specifically open the hairpin probe 1(HP1) labeled on the gold electrode (GE) surface through strand displacement reaction. Thus the exposed loop region of HP1 can act as an initiator sequence to activate the hybridization chain reaction (HCR) between two kinetically trapped hairpin probes: HP2 immobilized on the GE surface and biotin labeled HP3 in solution. Cascade HCR leads to the formation of DNA “nano-bridge” tethered to the GE surface with a great deal of “piers”. Upon addition of avidin-modified horseradish peroxidase (HRP), numerous HRP were bound to the formed “nano-bridge” through biotin-avidin interaction to arouse tremendous current signal. In theory, only a single miR-21 is able to trigger the continuous HCR between HP2 and HP3 until all of the HP2 are exhausted. Therefore the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with the detection limit down to 168 amol/L, as well as little cross-hybridization even at the single-base-mismatched level. Successful attempts were also made in the detection of exosomal miR-21 obtained from the MCF-7 of breast cancer cell line. To our knowledge, this is the first attempt to built horizontal DNA nano-structure on the electrode surface for exosomal miRNAs detection. In a word, the high sensitivity, selectivity, low cost make the proposed method hold great potential application for early point-of-care (POC) diagnostics of cancer.     

Ionic liquid–graphene hybrid nanosheets-based electrochemical sensor for sensitive detection of methyl parathion

In this work, ionic liquid–graphene nanosheets (IL–GNs) were synthesised and used as an enhanced material for sensitive detection of methyl parathion (MP) by electrochemical method. IL–GNs were characterised by UV–Vis spectroscopy, transmission electron microscopy (TEM), X-ray photo-electron spectroscopy (XPS), Fourier transform Infrared (FT-IR) spectroscopy and Raman spectroscopy, which confirmed that IL was successfully covered on the surface of GNs. Significantly, due to the coupling of excellent properties of GNs and IL, the IL–GNs-modified glassy carbon electrode (IL–GNs/GCE) showed higher signals for MP response than the GNs/GCE and bare GCE. At the IL–GNs/GCE, the peak currents increase linearly with the concentration of MP in the range of 5.3 ng/mL to 2.6 μg/mL with the detection limit of 1.1 ng/mL, which was better than other enzyme-based and enzymeless sensors. The IL–GNs-based electrochemical sensor was also successfully demonstrated for the detection of water sample with satisfactory results. Furthermore, the proposed electrochemical sensor exhibited satisfied stability and reproducibility. The simple sensing platform can be extended to detect other organophosphate pesticide.     

Sensitive detection of human breast cancer cells based on aptamer–cell–aptamer sandwich architecture

Breast cancer is one of the most critical threats to the health of women, and the development of new methods for early diagnosis is urgently required, so this paper reports a method to detect Michigan cancer foundation-7 (MCF-7) human breast cancer cells with considerable sensitivity and selectivity by using electrochemical technique. In this method, a mucin 1 (MUC1)-binding aptamer is adopted to recognize MCF-7 human breast cancer cells, while enzyme labeling is employed to produce amplified catalytic signals. The molecular recognition and the signal amplification are elaborately integrated by fabricating an aptamer–cell–aptamer sandwich architecture on an electrode surface, thus a biosensor for the detection of MCF-7 is fabricated based on the architecture. The detection range can be from 100 to 1 × 10⁷ cells, and the detection limit can be as low as 100 cells. The method is also cost-effective and conveniently operated, implying potential help for the development of early diagnosis of breast cancer.     

Ganglioside–liposome immunoassay for the detection of botulinum toxin

A rapid and highly sensitive receptor immunoassay for botulinum toxin (BT) has been developed using ganglioside-incorporated liposomes. Botulism outbreaks are relatively rare, but their results can be very severe, usually leading to death from respiratory failure. To exert their toxicity, the biological toxins must first bind to receptors on the cell surface, and the trisialoganglioside GT1b has been identified as the cell receptor for BT. Therefore, in this study, GT1b was used to prepare the ganglioside–liposomes by spontaneous insertion into the phospholipid bilayer. In a sandwich-based, hybrid receptor immunoassay, BT is detected as a colored band on a nitrocellulose membrane strip, where BT bound to the GT1b-liposomes are captured by anti-BT antibodies immobilized in a band across the strip. The intensity of the colored band can be visually estimated, or measured by densitometry using computer software. The limit of detection (LOD) for BT in the lateral-flow assay system was 15 pg mL^–1, which is comparable to the limits of detection achieved with the most sensitive assays previously reported. However, this rapid assay can be completed in less than 20 min. These results demonstrate that the sandwich assay using GT1b-liposomes for detection of BT is rapid and very sensitive, suggesting the possibility for detecting BT in field screening, simply and reliably, without the need for complex instrumentation.     

An electrochemical aptasensor based on cu2+-induced signal amplification strategy for the detection of ochratoxin aEI北大核心CSCD

A novel electrochemical aptasensor based on a Cu2+-induced signal amplification strategy was constructed for the rapid, sensitive and specific detection of ochratoxin A （OTA）. The OTA aptamer with poly （T） was hybridized with the captured DNA probe on the electrode surface. In the presence of Cu2+ and ascorbic acid, the end of poly（T） was used as a template to in situ grow copper nanoclusters （Cu NCs）. In the absence of targeted OTA, the gold electrodes after decorating Cu NCs were immersed into an acidic environment to release Cu2+. After enriching Cu2+ at a potential of − 1.6 V, the strongest current value of copper was recorded by measuring differential pulse voltammetry （DPV）. In the presence of OTA, the OTA aptamer was tightly bound to the target OTA. The OTA aptamer broke away from the electrode to reduce the growth of Cu NCs, resulting in lower DPV current response. This proposed method was employed to detect OTA with linear range from 0.1 to 50.0 ng/mL, and the detection limit was 41.2 pg/mL. The Cu2+-induced electrochemical aptasensor can be further applied in the analysis of target OTA in coffee solution samples. © 2023, Youke Publishing Co.,Ltd. All rights reserved.     

A new electrochemical method for DNA sequence detection with homogeneous hybridization based on host–guest recognition technology

This communication reports on a new electrochemical method to detect the hybridization specificity by using host–guest recognition technique. A hairpin DNA with dabcyl-labeled at its 3′ and NH₂ group at 5′ terminal was combined with CdS nanoparticle to construct a double-labeled probe (DLP), which could selectively hybridize with its target DNA in homogeneous solution. A β-CD modified Poly(N-acetylaniline) glassy carbon electrode was used for capturing the dabcyl label in DLP. When without binding with target DNA, the DLP kept its stem-loop structure which shielded the dabcyl molecule due to the loop of the hairpin DNA and CdS nanoparticle blocking dabcyl enter into the cavity of these β-CD molecules on the electrode. However, in present of complementary sequence, the target-binding DLP was incorporated into double stranded DNA, causing the DLP’s loop-stem structure opened and then the dabcyl was easily captured by the β-CD modified electrode. During electrochemical measurement, the signal from the dissolved Cd²⁺ was used for target DNA quantitative analysis.     

Gold–platinum alloy nanowires as highly sensitive materials for electrochemical detection of hydrogen peroxide

The exploitation of the unique electrical properties of nanowires requires an effective assembly of nanowires as functional materials on a signal transduction platform. This paper describes a new strategy to assemble gold–platinum alloy nanowires on microelectrode devices and demonstrates the sensing characteristics to hydrogen peroxide. The alloy nanowires have been controllably electrodeposited on microelectrodes by applying an alternating current. The composition, morphology and alloying structures of the nanowires were characterized, revealing a single-phase alloy characteristic, highly monodispersed morphology, and controllable bimetallic compositions. The alloy nanowires were shown to exhibit electrocatalytic response characteristics for the detection of hydrogen peroxide, exhibiting a high sensitivity, low detection limit, and fast response time. The nanowire's response mechanism to hydrogen peroxide is also discussed in terms of the synergistic activity of the bimetallic binding sites, which has important implications for a better design of functional nanowires as sensing materials for a wide range of applications.     

Label-free monitoring of the thrombin–aptamer recognition reaction using an array of nanochannels coupled with electrochemical detection

A sensitive and label-free method of monitoring the thrombin–aptamer recognition reaction has been developed using an array of nanochannels coupled with an electrochemical detection technique. Due to the highly amplified ion current produced by an array of nanochannels compared to a single nanochannel/pore, a significant increase in detection sensitivity has been achieved.     

An intimately bonded titanate nanotube–polyaniline–gold nanoparticle ternary composite as a scaffold for electrochemical enzyme biosensors

In this work, titanate nanotubes (TNTs), polyaniline (PANI) and gold nanoparticles (GNPs) were assembled to form a ternary composite, which was then applied on an electrode as a scaffold of an electrochemical enzyme biosensor. The scaffold was constructed by oxidatively polymerising aniline to produce an emeraldine salt of PANI on TNTs, followed by gold nanoparticle deposition. A novel aspect of this scaffold lies in the use of the emeraldine salt of PANI as a molecular wire between TNTs and GNPs. Using horseradish peroxidase (HRP) as a model enzyme, voltammetric results demonstrated that direct electron transfer of HRP was achieved at both TNT-PANI and TNT-PANI-GNP-modified electrodes. More significantly, the catalytic reduction current of H₂O₂ by HRP was ∼75% enhanced at the TNT-PANI-GNP-modified electrode, compared to that at the TNT-PANI-modified electrode. The heterogeneous electron transfer rate constant of HRP was found to be ∼3 times larger at the TNT-PANI-GNP-modified electrode than that at the TNT-PANI-modified electrode. Based on chronoamperometric detection of H₂O₂, a linear range from 1 to 1200 μM, a sensitivity of 22.7 μA mM⁻¹ and a detection limit of 0.13 μM were obtained at the TNT-PANI-GNP-modified electrode. The performance of the biosensor can be ascribed to the superior synergistic properties of the ternary composite.     

Multiplex sensor for detection of different metal ions based on on–off of fluorescent gold nanoclusters

In this study, a multiplex fluorescence sensor for successive detection of Fe³⁺, Cu²⁺ and Hg²⁺ ions based on “on–off” of fluorescence of a single type of gold nanoclusters (Au NCs) is described. Any of the Fe³⁺, Cu²⁺ and Hg²⁺ ions can cause quenching fluorescence of Au NCs, which established a sensitive sensor for detection of these ions respectively. With the introduction of ethylene diamine tetraacetic acid (EDTA) to the system of Au NCs and metal ions, a restoration of fluorescence may be found with the exception of Hg²⁺. A highly selective detection of Hg²⁺ ion is, thus, achieved by masking Fe³⁺ and Cu²⁺. On the other hand, the masking of Fe³⁺ and Cu²⁺ leads to the enhancement of fluorescence of Au NCs, which in turn provides an approach for successive determination of Fe³⁺ and Cu²⁺ based on “on–off” of fluorescence of Au NCs. Moreover, this assay was applied to the successful detection of Fe³⁺, Cu²⁺ and Hg²⁺ in fish, a good linear relationship was found between these metal ions and the degree of quenched fluorescent intensity. The dynamic ranges of Hg²⁺, Fe³⁺ and Cu²⁺ were 1.96 × 10⁻¹⁰–1.01 × 10⁻⁹, 1.28 × 10⁻⁷–1.27 × 10⁻⁶ and 1.2 × 10⁻⁷–1.2 × 10⁻⁶ M with high sensitivity (the limit of detection of Fe³⁺ 2.0 × 10⁻⁸ M, Cu²⁺ 1.9 × 10⁻⁸ M and Hg²⁺ 2 × 10⁻¹⁰ M). These results indicate that the assay is suitable for sensitive detection of these metal ions even under the coexistence, which can not only determine all three kinds of metal ions successively but also of detecting any or several kinds of metal ions.     

A Ti3C2TX/Pt–Pd based amperometric biosensor for sensitive cancer biomarker detection

The detection of cancer biomarkers is of great significance for the early screening of cancer. Detecting the content of sarcosine in blood or urine has been considered to provide a basis for the diagnosis of prostate cancer. However, it still lacks simple, high-precision and wide-ranging sarcosine detection methods. In this work, a Ti₃C₂T_X/Pt–Pd nanocomposite with high stability and excellent electrochemical performance has been synthesized by a facile one-step alcohol reduction and then used on a glassy carbon electrode (GCE) with sarcosine oxidase (SO_x) to form a sarcosine biosensor (GCE/Ti₃C₂T_X/Pt–Pd/SO_x). The prominent electrocatalytic activity and biocompatibility of Ti₃C₂T_X/Pt–Pd enable the SO_x to be highly active and sensitive to sarcosine. Under the optimized conditions, the prepared biosensor has a wide linear detection range to sarcosine from 1 to 1000 µM with a low limit of detection of 0.16 µM (S/N = 3) and a sensitivity of 84.1 µA/mM cm². Besides, the reliable response in serum samples shows its potential in the early diagnosis of prostate cancer. More importantly, the successful construction and application of the amperometric biosensor based on Ti₃C₂T_X/Pt–Pd will provide a meaningful reference for detecting other cancer biomarkers.