Design of an electrochemical aptasensor in the presence of an array of gold nanostructure and a GO-MWCNTs nanocomposite: application in diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is considered one of the main progressive chronic diseases in elderly individuals. Early diagnosis using related biomarkers, specifically beta-amyloid peptide (Aß), allows finding expected treatment routes. Here, we developed an electrochemical aptasensing platform for AD by employing a glassy carbon electrode (GCE) modified with a layer of jagged gold (JG) nanostructure (diameter: 60-185 nm) and graphene oxide-carboxylic acid functionalized multiwalled carbon nanotubes (GO-c-MWCNTs) nanocomposite. These surface modifications acted as the signal amplifier and provided an optimum nano-interface substrate for immobilizing aptamer strands. The measurements of Aß were performed via differential pulse voltammetry (DPV), and the aptasensor detected the analyte in a linear range from 0.1 pg mL-1 to 1 ng mL-1, with an estimated limit of detection (LOD) of about 0.088 pg mL-1 (S/N = 3). The aptasensor showed sufficient stability (11 days), reversibility (three times), and reproducibility (five times re-fabrication with relative standard deviation (RSD): 1.27). The potential interfering agents showed negligible impact on the sensing performance. Finally, the application of the aptasensor was evaluated in the presence of 10 serum samples, and the recovery values were from 93 to 110.1%.

3D-printed sensor decorated with nanomaterials by CO2 laser ablation and electrochemical treatment for non-enzymatic tyrosine detection.

The combination of CO2 laser ablation and electrochemical surface treatments is demonstrated to improve the electrochemical performance of carbon black/polylactic acid (CB/PLA) 3D-printed electrodes through the growth of flower-like Na2O nanostructures on their surface. Scanning electron microscopy images revealed that the combination of treatments ablated the electrode's polymeric layer, exposing a porous surface where Na2O flower-like nanostructures were formed. The electrochemical performance of the fabricated electrodes was measured by the reversibility of the ferri/ferrocyanide redox couple presenting a significantly improved performance compared with electrodes treated by only one of the steps. Electrodes treated by the combined method also showed a better electrochemical response for tyrosine oxidation. These electrodes were used as a non-enzymatic tyrosine sensor for quantification in human urine samples. Two fortified urine samples were analyzed, and the recovery values were 106 and 109%. The LOD and LOQ for tyrosine determination were 0.25 and 0.83 µmol L-1, respectively, demonstrating that the proposed devices are suitable sensors for analyses of biological samples, even at low analyte concentrations.

Paper-based electrochemical biosensors for the diagnosis of viral diseases.

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented.

Screen-Printed Technologies Combined with Flow Analysis Techniques: Moving from Benchtop to Everywhere.

Screen-printed electrodes (SPEs) coupled with flow systems have been reported in recent decades for an ever-growing number of applications in modern electroanalysis, aiming for portable methodologies. The information acquired through this combination can be attractive for future users with basic knowledge, especially due to the increased measurement throughput, reduction in reagent consumption and minimal waste generation. The trends and possibilities of this set rely on the synergistic behavior that maximizes both SPE and flow analyses characteristics, allowing mass production and automation. This overview addresses an in-depth update about the scope of samples, target analytes, and analytical throughput (injections per hour, limits of detection, linear range, etc.) obtained by coupling injection techniques (FIA, SIA, and BIA) with SPE-based electrochemical detection.

Electrochemical (Bio)Sensors Enabled by Fused Deposition Modeling-Based 3D Printing: A Guide to Selecting Designs, Printing Parameters, and Post-Treatment Protocols.

The 3D printing (or additive manufacturing, AM) technology is capable to provide a quick and easy production of objects with freedom of design, reducing waste generation. Among the AM techniques, fused deposition modeling (FDM) has been highlighted due to its affordability, scalability, and possibility of processing an extensive range of materials (thermoplastics, composites, biobased materials, etc.). The possibility of obtaining electrochemical cells, arrays, pieces, and more recently, electrodes, exactly according to the demand, in varied shapes and sizes, and employing the desired materials has made from 3D printing technology an indispensable tool in electroanalysis. In this regard, the obtention of an FDM 3D printer has great advantages for electroanalytical laboratories, and its use is relatively simple. Some care has to be taken to aid the user to take advantage of the great potential of this technology, avoiding problems such as solution leakages, very common in 3D printed cells, providing well-sealed objects, with high quality. In this sense, herein, we present a complete protocol regarding the use of FDM 3D printers for the fabrication of complete electrochemical systems, including (bio)sensors, and how to improve the quality of the obtained systems. A guide from the initial printing stages, regarding the design and structure obtention, to the final application, including the improvement of obtained 3D printed electrodes for different purposes, is provided here. Thus, this protocol can provide great perspectives and alternatives for 3D printing in electroanalysis and aid the user to understand and solve several problems with the use of this technology in this field.

Wearable soft electrochemical microfluidic device integrated with iontophoresis for sweat biosensing.

A soft and flexible wearable sweat epidermal microfluidic device capable of simultaneously stimulating, collecting, and electrochemically analyzing sweat is demonstrated. The device represents the first system integrating an iontophoretic pilocarpine delivery system around the inlet channels of epidermal polydimethylsiloxane (PDMS) microfluidic device for sweat collection and analysis. The freshly generated sweat is naturally pumped into the fluidic inlet without the need of exercising. Soft skin-mounted systems, incorporating non-invasive, on-demand sweat sampling/analysis interfaces for tracking target biomarkers, are in urgent need. Existing skin conformal microfluidic-based sensors for continuous monitoring of target sweat biomarkers rely on assays during intense physical exercising. This work demonstrates the first example of combining sweat stimulation, through transdermal pilocarpine delivery, with sample collection through a microfluidic channel for real-time electrochemical monitoring of sweat glucose, in a fully integrated soft and flexible multiplexed device which eliminates the need of exercising. The on-body operational performance and layout of the device were optimized considering the fluid dynamics and evaluated for detecting sweat glucose in several volunteers. Furthermore, the microfluidic monitoring device was integrated with a real-time wireless data transmission system using a flexible electronic board PCB conformal with the body. The new microfluidic platform paves the way to real-time non-invasive monitoring of biomarkers in stimulated sweat samples for diverse healthcare and wellness applications.

Electrochemical nanobiosensors equipped with peptides: a review.

Recent research in the field of electrochemical biosensors equipped with peptides and nanomaterials have been categorized, reviewed, and critically analyzed. Indeed, using these innovative biosensors can revolutionize biomedical diagnostics in the future. Saving lives, time, and money in this field will be considered as some main benefits of this type of diagnosis. Here, these biosensors have been categorized and evaluated in four main sections. In the first section, the focus is on investigating the types of electrochemical peptide-based nanobiosensors applied to detect pathogenic microorganisms, microbial toxins, and viruses. In the second section, due to the importance of rapid diagnosis and prognosis of various cancers, the electrochemical peptide-based nanobiosensors designed to detect cancer biomarkers have been reviewed and analyzed. In the third section, the electrochemical peptide-based nanobiosensors, which were applied to detect the essential and effective biomolecules in the various diseases, and health control, including enzymes, hormones, biomarkers, and other biomolecules, have been considered. Finally, using a comprehensive analysis, all the used elements in these biosensors have been presented as conceptual diagrams that can effectively guide researchers in future developments. The essential factors in evaluating and analyzing these electrochemical peptide-based nanobiosensors such as analyte, peptide sequence, functional groups interacted between the peptide sequences and other biosensing components, the applied nanomaterials, diagnostic techniques, detection range, and limit of detection have also been included. Other analyzable items such as the type of used redox marker and the location of the peptide sequence against the signal transducer were also considered.

Recent advances in electroanalytical drug detection by porphyrin/phthalocyanine macrocycles: developments and future perspectives.

Porphyrins and phthalocyanines are promising π-conjugated compounds with fantastic photochemical and electrochemical properties which are present in nature in more systems than we are generally aware. The electrochemical properties of these large aromatic molecules are also unique, endowing them with the ability to catalyze a wide range of redox reactions. The macrocycle core of these molecules is extremely favorable for the complexation of several metal ions, resulting in molecules with tunable properties. Porphyrins and phthalocyanines are able to form highly organized films, with high conductivity and great robustness and their use was explored to build a great number of electrochemical and photoelectrochemical sensors for many varied applications, one among them being drug analysis. This review will focus on the potential of the electrodes modified with attractive porphyrins and phthalocyanines for this application. The papers published in the last 3 years were closely evaluated.

Additively manufactured carbon/black-integrated polylactic acid 3Dprintedsensor for simultaneous quantification of uric acid and zinc in sweat.

For the first time the development of an electrochemical method for simultaneous quantification of Zn2+ and uric acid (UA) in sweat is described using an electrochemically treated 3D-printed working electrode. Sweat analysis can provide important information about metabolites that are valuable indicators of biological processes. Improved performance of the 3D-printed electrode was achieved after electrochemical treatment of its surface in an alkaline medium. This treatment promotes the PLA removal (insulating layer) and exposes carbon black (CB) conductive sites. The pH and the square-wave anodic stripping voltammetry technique were carefully adjusted to optimize the method. The peaks for Zn2+ and UA were well-defined at around - 1.1 V and + 0.45 V (vs. CB/PLA pseudo-reference), respectively, using the treated surface under optimized conditions. The calibration curve showed a linear range of 1 to 70 µg L-1 and 1 to 70 µmol L-1 for Zn2+ and UA, respectively. Relative standard deviation values were estimated as 4.8% (n = 10, 30 µg L-1) and 6.1% (n = 10, 30 µmol L-1) for Zn2+ and UA, respectively. The detection limits for Zn2+ and UA were 0.10 µg L-1 and 0.28 µmol L-1, respectively. Both species were determined simultaneously in real sweat samples, and the achieved recovery percentages were between 95 and 106% for Zn2+ and 82 and 108% for UA.

Uric acid electrochemical sensing in biofluids based on Ni/Zn hydroxide nanocatalyst.

A highly sensitive sensor for quantification of uric acid (UA) directly in body fluids (saliva and sweat) is reported, working at a potential as low as 0.0 V vs Ag/AgCl. New mixed hydroxide materials exhibiting stable electrocatalytic responses from alkaline to acidic media were prepared, their structure was thoroughly characterized, and the electrochemical properties of the modified FTO (fluorine-doped tin oxide) electrodes were evaluated for UA determination by cyclic voltammetry, chronoamperometry, and batch injection analysis. A very low limit of detection (2.3 × 10-8 mol L-1) with good repeatability (RSD = 3.2% for 30 successive analyses) was achieved based on a fast and simple BIA procedure. Finally, α-Ni0.75Zn0.25(OH)2 screen-printed electrodes (SPE) were developed for the measurement of UA directly in real saliva and sweat samples, without interference of ascorbic acid, acetaminophen, lactate, and glucose at their typical concentrations present in those body fluids, revealing high potential for application as disposable sensors in biological systems. Graphical abstract.

New Electrochemical Flow-Cell Configuration Integrated into a Three-Dimensional Microfluidic Platform: Improving Analytical Application in the Presence of Air Bubbles.

A newly configured electrochemical flow cell to be used for (end-channel) amperometric detection in a microfluidic device is presented. The design was assembled to place the reference electrode in a separated compartment, isolated from the flow in the microchannel, while the working and counter electrodes remain in direct contact with both compartments. Moreover, a three-dimensional coil-shaped microfluidic device was fabricated using a nonconventional protocol. Both devices working in association enabled us to solve the drawback caused by the discrete injection when the automatic micropipette was used. The high performance of the proposed electrochemical flow cell was demonstrated after in situ modifying the surface of the platinum working electrode with surfactant (e.g., using Tween 20 at 0.10%). As the reference electrode remained out of contact with the flowing solution, there was no trouble by air bubble formation (generated by accidental insertion or by presence of surfactants) throughout the measurements. This device was characterized regarding its analytical performance by evaluating the amperometric detection of acetaminophen, enabling determination from 6.60 to 66.0 µmol L-1. This issue is important since at high concentration (e.g., as assessed in clinical analysis) the acetaminophen is known to passivate the working electrode surfaces by electrogenerated products, impairing the accuracy of the electrochemical measurements.

Disposable Voltammetric Immunosensors Integrated with Microfluidic Platforms for Biomedical, Agricultural and Food Analyses: A Review.

Disposable immunosensors are analytical devices used for the quantification of a broad variety of analytes in different areas such as clinical, environmental, agricultural and food quality management. They detect the analytes by means of the strong interactions between antibodies and antigens, which provide concentration-dependent signals. For the herein highlighted voltammetric immunosensors, the analytical measurements are due to changes in the electrical signals on the surface of the transducers. The possibility of using disposable and miniaturized immunoassays is a very interesting alternative for voltammetric analyses, mainly, when associated with screen-printing technologies (screen-printed electrodes, SPEs), and microfluidic platforms. The aim of this paper is to discuss a carefully selected literature about different examples of SPEs-based immunosensors associated with microfluidic technologies for diseases, food, agricultural and environmental analysis. Technological aspects of the development of the voltammetric immunoassays such as the signal amplification, construction of paper-based microfluidic platforms and the utilization of microfluidic devices for point-of-care testing will be presented as well.

Single-Step Reagentless Laser Scribing Fabrication of Electrochemical Paper-Based Analytical Devices.

A single-step laser scribing process is used to pattern nanostructured electrodes on paper-based devices. The facile and low-cost technique eliminates the need for chemical reagents or controlled conditions. This process involves the use of a CO2 laser to pyrolyze the surface of the paperboard, producing a conductive porous non-graphitizing carbon material composed of graphene sheets and composites with aluminosilicate nanoparticles. The new electrode material was extensively characterized, and it exhibits high conductivity and an enhanced active/geometric area ratio; it is thus well-suited for electrochemical purposes. As a proof-of-concept, the devices were successfully employed for different analytical applications in the clinical, pharmaceutical, food, and forensic fields. The scalable and green fabrication method associated with the features of the new material is highly promising for the development of portable electrochemical devices.

Unveiling the structure of polytetraruthenated nickel porphyrin by Raman spectroelectrochemistry.

The structure of polytetraruthenated nickel porphyrin was unveiled for the first time by electrochemistry, Raman spectroelectrochemistry, and a hydroxyl radical trapping assay. The electrocatalytic active material, precipitated on the electrode surface after successive cycling of [NiTPyP{Ru(bipy)2Cl}4](4+) species in strong aqueous alkaline solution (pH 13), was found to be a peroxo-bridged coordination polymer. The electropolymerization process involves hydroxyl radicals (as confirmed by the characteristic set of DMPO/(•)OH adduct EPR peaks) as reaction intermediates, electrocatalytically generated in the 0.80-1.10 V range, that induce the formation of Ni-O-O-Ni coordination polymers, as evidenced by Raman spectroelectrochemistry and molecular modeling studies. The film growth is halted above 1.10 V due to the formation of oxygen gas bubbles.

Ultrasensitive Aptasensing Platform for the Detection of ß-Amyloid-42 Peptide Based on MOF Containing Bimetallic Porphyrin Graphene Oxide and Gold Nanoparticles.

The prompt detection of diseases hinges on the accessibility and the capability to identify relevant biomarkers. The integration of aptamers and the incorporation of nanomaterials into signal transducers have not only expedited but also enhanced the development of nanoaptasensors, enabling heightened sensitivity and selectivity. Here, the bimetallic nickel-cobalt-porphyrin metal-organic framework ((Ni + Cu)TPyP MOF) is regarded as an electron mediator, immobilization platform for an Alzheimer aptamer and to increase the electrochemical signal for the detection of the main biomarker of Alzheimer's disease (AD), amyloid ß (Aß-42). Furthermore, the ((Ni + Cu)TPyP MOF) was combined with reduced graphene oxide (rGO) and gold nanoparticles (AuNPs), on a gold electrode (GE) to provide an efficient interface for immobilizing aptamer strands. Concurrently, the incorporation of rGO and AuNPs imparts enhanced electrical conductivity and efficacious catalytic activity, establishing them as adept electrochemical indicators. Owing to the superior excellent electrical conductivity of rGO and AuNPs, coupled with the presence of ample mesoporous channels and numerous Ni and Cu metal sites within (Ni + Cu)TPyP MOF, this nanostructure with abundant functional groups is proficient in immobilizing a substantial quantity of aptamer. These interactions are achieved through robust π-π stacking and electrostatic interactions, alongside the high affinity between the thiol group of the aptamer and AuNPs concurrently. The as-prepared ternary (Au@(Ni + Cu)TPyP MOF/rGO) nanostructure electrode exhibited an enhancement in its electrochemically active surface area of about 7 times, compared with the bare electrode and the Aß-42 redox process is highly accelerated, so the peak currents are significantly higher than those obtained with bare GE substrate. Under the optimized conditions, the designed aptasensor had the quantitative detection of Aß-42 with a low detection limit of 48.6 fg mL-1 within the linear range of 0.05 pg mL-1 to 5 ng mL-1 by differential pulse voltammetry (DPV), accompanied by precise reproducibility, satisfactory stability (95.6% of the initial activity after 10 days), and minimal impact of interfering agents. Recorded results in human blood plasma demonstrated the high efficacy of porphyrin MOF system sensing even in the clinical matrix. The great performance of this aptasensor indicates that our new design of Au@(Ni + Cu)TPyP MOF/rGO nanostructure provides more opportunities for the detection of chemical signals in early diagnosis of Alzheimer's disease.

Electrochemical microfluidic immunosensor with graphene-decorated gold nanoporous for T-2 mycotoxin detection.

T-2 is one of the most potent cytotoxic food-borne mycotoxins. In this work, we have developed and characterized an electrochemical microfluidic immunosensor for T-2 toxin quantification in wheat germ samples. T-2 toxin detection was carried out using a competitive immunoassay method based on monoclonal anti-T-2 antibodies immobilized on the poly(methyl methacrylate) (PMMA) microfluidic central channel. The platinum wire working electrode at the end of the channel was in situ modified by a single-step electrodeposition procedure with reduced graphene oxide (rGO)-nanoporous gold (NPG). T-2 toxin in the sample was allowed to compete with T-2-horseradish peroxidase (HRP) conjugated for the specific recognizing sites of immobilized anti-T-2 monoclonal antibodies. The HRP, in the presence of hydrogen peroxide (H2O2), catalyzes the oxidation of 4-tert-butylcatechol (4-TBC), whose back electrochemical reduction was detected on the nanostructured electrode at -0.15 V. Thus, at low T-2 concentrations in the sample, more enzymatically conjugated T-2 will bind to the capture antibodies, and, therefore, a higher current is expected. The detection limits found for electrochemical immunosensor, and commercial ELISA procedure were 0.10 µg kg-1 and 10 µg kg-1, and the intra- and inter-assay coefficients of variation were below 5.35% and 6.87%, respectively. Finally, our microfluidic immunosensor to T-2 toxin will significantly contribute to faster, direct, and secure in situ analysis in agricultural samples.

Glassy carbon electrode modified with a film of tetraruthenated nickel(ii) porphyrin located in natural smectite clay's interlayer for the simultaneous sensing of dopamine, acetaminophen and tryptophan.

A supramolecular complex µ-meso-tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)2Cl}4]4+) was intercalated into the interlayer space of natural smectite clay (shortened as Ba) collected in a Cameroonian deposit at Bagba hill. Physicochemical characterization of the resulting material using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) confirmed the intercalation of the porphyrin within the interlayer space of the clay. The intercalated clay was then used to form a stable thin film onto a glassy carbon electrode (GCE) by drop casting a suspension of the hybrid material. The GCE modified with the intercalated organoclay endowed the electrode with a larger electrochemically active surface area, good stability, high selectivity, and sensitivity toward dopamine (DA), acetaminophen (AC) and tryptophan (Trp). In addition, it was observed that the modified electrodes exhibited good and pH-dependent electrocatalytic properties toward these analytes. The simultaneous determination of DA, AC and Trp at [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE was thus possible without the interference of one analyte on the others, and the resulting calibration curve exhibits two segments for the three analytes. For DA, AC and Trp, the detection limits were found to be 0.8 µM, 0.3 µM and 0.3 µM, respectively. The [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE modified electrodes were successfully applied for the determination of AC in Paracetamol, a commercial product, and Trp in real pharmaceutical formulation samples.

Fast simultaneous determination of trimethoprim and sulfamethoxazole by capillary zone electrophoresis with capacitively coupled contactless conductivity detection.

The association of trimethoprim and sulfamethoxazole is a very effective with antibiotic properties, and commonly used in the treatment of a variety of infections. Due to the importance in diseases treatment of humans and also of animals, the development of methods for their quantification in commercial formulations is highly desirable. In the present study, a rapid method for simultaneous determination of these compounds using CE with capacitively coupled contactless conductivity detection was developed. A favorable working region for both analytes was from 12.5 to 200 µmol/L (linear responses with R > 0.999 for N = 5). Other parameters calculated were sensitivity (1.28 ± 0.10/1.45 ± 0.11) min/(µmol L), RSD (4.5%/2.0%), and LOD (1.1/3.3) µmol/L for trimethoprim and sulfamethoxazole, respectively. Under this condition, the total run time was only 2.6 min. The proposed method was applied to the determination of trimethoprim and sulfamethoxazole in commercial samples and the results were compared to those obtained by using a HPLC pharmacopoeia method. This new method is advantageous for quality-control analyses of trimethoprim and sulfamethoxazole in pharmaceuticals samples, because it is rapid and precise. Moreover, it is less laborious and demands minimum amounts of reagents in comparison to the recommended method.

Recent advances in electrochemical nanomaterial-based aptasensors for the detection of cancer biomarkers.

New technologies have provided suitable tools for rapid diagnosis of cancer which can reduce treatment costs and even increase patients' survival rates. Recently, the development of electrochemical aptamer-based nanobiosensors has raised great hopes for early, sensitive, selective, and low-cost cancer diagnosis. Here, we reviewed the flagged recent research (2021-2023) developed as a series of biosensors equipped with nanomaterials and aptamer sequences (nanoaptasensors) to diagnose/prognosis of various types of cancers. Equipping these aptasensors with nanomaterials and using advanced biomolecular technologies have provided specified biosensing interfaces for more optimal and reliable detection of cancer biomarkers. The primary intention of this review was to present and categorize the latest innovations used in the design of these diagnostic tools, including the hottest surface modifications and assembly of sensing bioplatforms considering diagnostic mechanisms. The main classification is based on applying various nanomaterials and sub-classifications considered based on the type of analyte and other vital features. This review may help design subsequent electrochemical aptasensors. Likewise, the up-to-date status, remaining limitations, and possible paths for translating aptasensors to clinical cancer assay tools can be clarified.

Electrochemical Immunosensors Developed for Amyloid-Beta and Tau Proteins, Leading Biomarkers of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aß), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from the amyloid precursor protein (APP), are the leading biomarkers for accurate and early diagnosis of AD due to their central role in disease pathology, their correlation with disease progression, their diagnostic value, and their implications for therapeutic interventions. Their detection and monitoring contribute significantly to understanding AD and advancing clinical care. Available diagnostic techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are mainly used to validate AD diagnosis. However, these methods are expensive, yield results that are difficult to interpret, and have common side effects such as headaches, nausea, and vomiting. Therefore, researchers have focused on developing cost-effective, portable, and point-of-care alternative diagnostic devices to detect specific biomarkers in cerebrospinal fluid (CSF) and other biofluids. In this review, we summarized the recent progress in developing electrochemical immunosensors for detecting AD biomarkers (Aß and p-tau protein) and their subtypes (AßO, Aß(1-40), Aß(1-42), t-tau, cleaved-tau (c-tau), p-tau181, p-tau231, p-tau381, and p-tau441). We also evaluated the key characteristics and electrochemical performance of developed immunosensing platforms, including signal interfaces, nanomaterials or other signal amplifiers, biofunctionalization methods, and even primary electrochemical sensing performances (i.e., sensitivity, linear detection range, the limit of detection (LOD), and clinical application).