Biosensor Chip Research Articles

Biosensor Chip for Point-of-Care Diagnostics: Carbon Nanotube Sensing Platform for Bacterial Detection and Identification

Biosensor Chip for Point-of-Care Diagnostics: Carbon Nanotube Sensing Platform for Bacterial Detection and Identification

A miniprotein receptor electrochemical biosensor chip based on quantum dots.

Recently protein binders have emerged as a promising substitute for antibodies due to their high specificity and low cost. Herein, we demonstrate an electrochemical biosensor chip through the electronic labelling strategy using lead sulfide (PbS) colloidal quantum dots (CQDs) and the unnatural SARS-CoV-2 spike miniprotein receptor LCB. The unnatural receptor can be utilized as a molecular probe for the construction of CQD-based electrochemical biosensor chips, through which the specific binding of LCB and the spike protein is transduced to sensor electrical signals. The biosensor exhibits a good linear response in the concentration range of 10 pg mL-1 to 1 μg mL-1 (13.94 fM to 1.394 nM) with the limit of detection (LOD) being 3.31 pg mL-1 (4.607 fM for the three-electrode system) and 9.58 fg mL-1 (0.013 fM for the HEMT device). Due to the high sensitivity of the electrochemical biosensor, it was also used to study the binding kinetics between the unnatural receptor LCB and spike protein, which has achieved comparable results as those obtained with commercial equipment. To the best of our knowledge, this is the first example of using a computationally designed miniprotein receptor based on electrochemical methods, and it is the first kinetic assay performed with an electrochemical assay alone. The miniprotein receptor electrochemical biosensor based on QDs is desirable for fabricating high-throughput, large-area, wafer-scale biochips.

An rGO-doped laser induced graphene electrochemical biosensor for highly sensitive exosome detection

An electrochemical biosensing chip using rGO-modified LIG was developed to detect exosomes for breast cancer diagnostics.

Large-area grown ultrathin molybdenum oxides for label-free sensitive biomarker detection.

The rise of two-dimensional (2D) materials has provided a confined geometry and yielded methods for guiding electrons at the nanoscale level. 2D material-enabled electronic devices can interact and transduce the subtle charge perturbation and permit significant advancement in molecule discrimination technology with high accuracy, sensitivity, and specificity, leaving a significant impact on disease diagnosis and health monitoring. However, high-performance biosensors with scalable fabrication ability and simple protocols have yet to be fully realized due to the challenges in wafer-scale 2D film synthesis and integration with electronics. Here, we propose a molybdenum oxide (MoOx)-interdigitated electrode (IDE)-based label-free biosensing chip, which stands out for its wafer-scale dimension, tunability, ease of integration and compatibility with the complementary metal-oxide-semiconductor (CMOS) fabrication. The device surface is biofunctionalized with monoclonal anti-carcinoembryonic antigen antibodies (anti-CEA) via the linkage agent (3-aminopropyl)triethoxysilane (APTES) for carcinoembryonic antigen (CEA) detection and is characterized step-by-step to reveal the working mechanism. A wide range and real-time response of the CEA concentration from 0.1 to 100 ng mL-1 and a low limit of detection (LOD) of 0.015 ng mL-1 were achieved, meeting the clinical requirements for cancer diagnosis and prognosis in serum. The MoOx-IDE biosensor also demonstrates strong surface affinity towards molecules and high selectivity using L-cysteine (L-Cys), glycine (Gly), glucose (Glu), bovine serum albumin (BSA), and immunoglobulin G (IgG). This study showcases a simple, scalable, and low-cost strategy to create a nanoelectronic biosensing platform to achieve high-performance cancer biomarker discrimination capabilities.

Ultrasensitive Biochemical Sensing Platform Enabled by Directly Grown Graphene on Insulator.

To fabricate label-free and rapid-resulting semiconducting biosensor devices incorporating graphene, it is pertinent to directly grow uniform graphene films on technologically important dielectric and semiconducting substrates. However, it has long been intuitively believed that the nonideal disordered structures formed during direct growth, and the resulted inferior electrical properties will inevitably lead to deteriorated sensing performance. Here, graphene biosensor chips are constructed based on direct plasma-enhanced chemical vapor deposition (PECVD) grown graphene on a 4-inch silicon wafer with excellent film uniformity and high yield. To surprise, optimal operations of graphene biosensors permit ultrasensitive detection of SARS-CoV-2 virus nucleocapsid protein with dilutions down to sub-femtomolar concentrations. Such impressive limit of detection (LOD) is comparable to or even outperforms that of the state-of-the-art biosensor devices based on high-quality graphene. Further noise spectral characterizations and analysis confirms that the LOD is limited by molecular diffusion and/or known interference signals such as drift and instability of the sensors, rather than the electrical merits of the graphene devices along. Hence, result sheds light on processing directly grown PECVD graphene into high-performance sensor devices with important economic benefits and social significance.

A self-driven, microfluidic, integrated-circuit biosensing chip for detecting four cardiovascular disease biomarkers

Cardiovascular diseases (CVDs) claimed the lives of nearly 21 million people worldwide in 2021, accounting for 30% of global deaths. However, one in five CVD patients is unaware that they have the disease, emphasizing the need for accurate biomarker monitoring. Herein we developed an integrated microfluidic system (IMS) for rapid quantification of four CVD biomarkers, including N-terminal pro B-type natriuretic peptide (NT-proBNP), fibrinogen, cardiac troponin I (cTnI), and C-reactive protein (CRP)- via aptamer-coated interdigitated electrodes (IDE) with integrated circuits (IC) and a self-driven IMS for sample treatment. The device was composed of plasma filtration, metering, and fluidic delay modules, and the former could extract 45% of plasma from a 20-μL blood sample; the metering module could quantify 5 μL of plasma within 90 s. Subsequently, the plasma was transported to a detection chamber, where IC-based IDE sensors made measurements within 5 min. The entire 15-min process allowed us to evaluate biomarkers across a wide dynamic range: NT-proBNP (0.1–10,000 pg/mL), fibrinogen (50-1,000 mg/dL), cTnI (0.1–10,000 pg/mL), and CRP (0.5-9 mg/L). Given that spiked blood samples were measured with reasonable accuracy (>80%), the IMS could see utility in CVD risk assessment and personalized medicine.

Large-scale plasmonic nanodisk array as a biosensing platform fabricated by transfer nanoprinting.

Surface plasmon resonance based on nanostructures has been a powerful analytical tool in rapid detection and analysis of biomolecules. However, the fabrication of nanostructure sensors, such as electron beam lithography and focused ion beam milling, has inherent defects as manufacturing cost, complex process flow, and small fabrication area. In this paper, using the transfer nanoprinting approach based on an ultrathin anodic aluminum oxide membrane, a centimeter-scale ordered periodic Ag-ZnS bilayer nanodisk on Au film with a low cost and simple process is fabricated. A surface plasmon polariton Bloch mode from nanodisk arrays is experimentally demonstrated at normal incident of light. The plasmonic platform exhibits an ideal refractive index bulk sensitivity of up to 438nm/RIU. Furthermore, by using a polyelectrolyte bilayer with well-defined thickness, the surface sensitivity of the biosensing platform is also investigated. The large-scale plasmonic bilayer nanoparticle biosensing platform has broad application prospects in development of low-cost and high-performance biosensing chips.

B-216 Development of a Point-of-care Multiplexed Room Temperature Stable Environmental Toxin Test

Abstract Background Hememics™ Biosensor System (HBS) is a platform technology enabling antigen and molecular testing in the field. The system consists of a reader, HemBox™, and a biosensing chip, HemChip™. The HemBox™ is a battery-operated, cell phone size with Bluetooth and WIFI module that can be integrated into the Health Management System. The biosensing chips can be programed with bio-receptors to detect pathogens in less than 5 min. This study presents performance characteristics of HBS as a rapid POC to detect toxins from environmental samples. Methods The testing protocol consists of insert a HemChip™ into the HemBox™ and mixing the sample with the buffer and apply a drop of this mixture to the chip. In less than 5 min, results are displayed on the screen of HemBox™ or transmitted to user’s cellphone via Bluetooth. Samples were prepared by spiking solutions of mud, serum, vegetable wash, and milk with Staphylococcal enterotoxin B (SEB) and ricin. Results HemChip™ was functionalized to recognize Ricin and SEB targets. For testing, these targets were mixed in various matrix. To achieve statistical significance, each sample tested represented a minimum of 10 data points. Conclusion Hememics™ Biosensor System (HBS) is designed to be the ultimate Portable Lab Diagnostics for field use. The ability to test for environmental toxins in the field is significant because it allows for quick and on-site detection of potentially harmful substances. Our biosensor system also eliminates the need for sample processing, collection and transportation, which can take significant time and resources. The results of field testing can be available almost immediately, allowing for prompt action to be taken in the case of high toxin levels.

RatioCRISPR: A ratiometric biochip based on CRISPR/Cas12a for automated and multiplexed detection of heteroplasmic SNPs in mitochondrial DNA

Mitochondrial genetic diseases are often characterized by heteroplasmic single nucleotide polymorphisms (SNPs) where both wild-type (WT) and mutant-type (MT) coexist, making detection of accurate SNP abundance critical for diagnosis. Here, we present RatioCRISPR, an automated ratiometric biochip sensor based on the CRISPR/Cas12a system for detecting multiple heteroplasmic SNPs in mitochondrial DNA (mtDNA). The ratiometric sensor output is only influenced by the relative abundance of WT and MT, with minimal impact from sample concentration. Biochips allow the simultaneous detection of multiple SNP sites for more accurate disease diagnosis. RatioCRISPR can accurately detect 8 samples simultaneously within 25 min with a limit of detection (LOD) of 15.7 aM. We successfully detected 13 simulated samples of three mtDNA point mutations (m.3460G>A, m.11778G>A, and m.14484T>C), which lead to Leber's hereditary optic neuropathy (LHON) and set a threshold (60%) of heteroplasmy to evaluate disease risk. This automated and accurate biosensor has broad applications in diagnosing multiple SNPs, especially those with heteroplasmic variations, making it an advanced and convenient tool for mtDNA disease diagnosis.

Ultrasensitive FET biosensor chip based on self-assembled organic nanoporous membrane for femtomolar detection of Amyloid-β.

Early diagnosis of Alzheimer's disease (AD) is critical for preventing disease progression, however, the diagnosis of AD remains challenging for most patients due to limitations of current sensing technologies. A common pathological feature found in AD-affected brains is the accumulation of Amyloid-β (Aβ) polypeptides, which lead to neurofibrillary tangles and neuroinflammatory plaques. Here, we developed a portable ultrasensitive FET biosensor chip based on a self-assembled nanoporous membrane for ultrasensitive detection of Aβ protein in complex environments. The microscale semiconductor channel was covered with a self-assembled organic nanoporous membrane modified by antibody molecules to pick up and amplify the Aβ protein signal. The nanoporous structure helps protect the sensitive channel from non-target proteins and improves its stability since no chemical functionalization process involved, largely reduces background noise of the sensing platform. When a bio-gated target is captured, the doping state of the polymer bulk could be tuned and amplified the strength of the weak signal, achieving ultrasensitive detecting performance (enabling the device to detect target protein less than 1fg/ml in 1µl sample). Moreover, the device simplifies the circuit connection by integrating all the connections on a 2cm × 2cm chip, avoiding expensive and complex manufacturing processes, and makes it usable for portable prognosis. We believe that this ultrasensitive, portable, low-cost Aβ sensor chip shows the great potential in the early diagnosis of AD and large-scale population screening applications.

Fabrication of graphene oxide-based pretreatment filter and Electrochemical-CRISPR biosensor for the field-ready cyanobacteria monitoring system

Microcystis aeruginosa (M. aeruginosa) cause the eutrophication of lakes and rivers. To effectively control the overgrowth of M. aeruginosa, a suitable measurement method should be required in the aquatic fields. To address this, we developed a field-ready cyanobacterial pretreatment device and an electrochemical clustered regularly interspaced short palindromic repeats (EC-CRISPR) biosensor. The cyanobacterial pretreatment device consists of a syringe, glass bead, and graphene oxide (GO) bead. Then, the M. aeruginosa dissolved in the freshwater sample was added to fabricated filter. After filtration, the purified gene was loaded onto a CRISPR-based electrochemical biosensor chip to detect M. aeruginosa gene fragments. The biosensor was composed of CRISPR/Cpf1 protein conjugated with MXene on an Au microgap electrode (AuMGE) integrated into a printed circuit board (PCB). This AuMGE/PCB system maximizes the signal-to-noise ratio, which controls the working and counter electrode areas requiring only 3 μL samples to obtain high reliability. Using the extracted M. aeruginosa gene with a pre-treatment filter, the CRISPR biosensor showed a limit of detection of 0.089 pg/μl in fresh water. Moreover, selectivity test and matrix condition test carried out using the EC-CRISPR biosensor. These handheld pre-treatment kit and biosensors can enable field-ready detection of CyanoHABs.

Localized surface plasmon resonance biosensor chip surface modification and signal amplifications toward rapid and sensitive detection of COVID-19 infections

We developed a multi-pronged approach to enhance the detection sensitivity of localized surface plasmon resonance (LSPR) sensor chips to detect SARS-CoV-2. To this end, poly(amidoamine) dendrimers were immobilized onto the surface of LSPR sensor chips to serve as templates to further conjugate aptamers specific for SARS-CoV-2. The immobilized dendrimers were shown to reduce surface nonspecific adsorptions and increase capturing ligand density on the sensor chips, thereby improving detection sensitivity. To characterize the detection sensitivity of the surface-modified sensor chips, SARS-CoV-2 spike protein receptor-binding domain was detected using LSPR sensor chips with different surface modifications. The results showed that the dendrimer-aptamer modified LSPR sensor chip exhibited a limit of detection (LOD) of 21.9 pM, a sensitivity that was 9 times and 152 times more sensitive than the traditional aptamer- or antibody-based LSPR sensor chips, respectively. In addition, detection sensitivity was further improved by combining rolling circle amplification product and gold nanoparticles to further amplify the detection signals by increasing both the target mass and plasmonic coupling effects. Using pseudo SARS-CoV-2 viral particles as detection targets, we demonstrated that this combined signal intensification approach further enhanced the detection sensitivity by 10 folds with a remarkable LOD of 148 vp/mL, making it one of the most sensitive SARS-CoV-2 detection assays reported to date. These results highlight the potential of a novel LSPR-based detection platform for sensitive and rapid detection of COVID-19 infections, as well as other viral infections and point-of-care applications.

One-step-one-pot hydrothermally derived metal-organic-framework-nanohybrids for integrated point-of-care diagnostics of SARS-CoV-2 viral antigen/pseudovirus utilizing electrochemical biosensor chip

The COVID-19 pandemic has become a global catastrophe, affecting the health and economy of the human community. It is required to mitigate the impact of pandemics by developing rapid molecular diagnostics for SARS-CoV-2 virus detection. In this context, developing a rapid point-of-care (POC) diagnostic test is a holistic approach to the prevention of COVID-19. In this context, this study aims at presenting a real-time, biosensor chip for improved molecular diagnostics including recombinant SARS-CoV-2 spike glycoprotein and SARS-CoV-2 pseudovirus detection based on one-step-one-pot hydrothermally derived CoFeBDCNH2-CoFe2O4 MOF-nanohybrids. This study was tested on a PalmSens-EmStat Go POC device, showing a limit of detection (LOD) for recombinant SARS-CoV-2 spike glycoprotein of 6.68 fg/mL and 6.20 fg/mL in buffer and 10% serum-containing media, respectively. To validate virus detection in the POC platform, an electrochemical instrument (CHI6116E) was used to perform dose dependent studies under similar experimental conditions to the handheld device. The results obtained from these studies were comparable indicating the capability and high detection electrochemical performance of MOF nanocomposite derived from one-step-one-pot hydrothermal synthesis for SARS-CoV-2 detection for the first time. Further, the performance of the sensor was tested in the presence of Omicron BA.2 and wild-type D614G pseudoviruses.

Transport effects in biochip sensors with redox cycling amplification

We report a study of transport effects on a microfluidic sensor-chip in which electrochemical sensing is amplified by redox cycling using an interdigitated electrode array (IDA). A full three-dimensional simulation-based model and a simple one-dimensional model for the transition velocity between the two regimes is presented. These models indicate that there exist two dominant regimes: one which is limited by redox cycling diffusion—a unique feature of IDAs— and another which is limited by convection and has dominant flow effects. The transition velocity between the two sensing regimes was found to be vflow[mmsec]=0.335L[μm]+0.04 which is similar to the prediction of vflow∝1L, obtained from the one-dimensional model.

A Numerical Study of Different Metal and Prism Choices in the Surface Plasmon Resonance Biosensor Chip for Human Blood Group Identification.

Optimized design of Surface plasmon resonance (SPR) based biosensor in terms of different metal choices and prisms are presented to the first time for the high precision detection of human blood group in near infrared wavelength range. The results are well compared with the earlier published gold coated silicon biosensor chip while discussing the pros and cons of various prism/metal choices. In this study buffer layer onto SPR active metal has been deployed to avoid the oxidation problem and contamination issue related with blood samples. Refractive index of blood samples has been considered in theoretical model based on the experimental data. Si prism has been found to be the best choice as a substrate material with combination of Al as a SPR active metal for blood group identification analysis. SPR dip slope (S), detection accuracy (D.A.) and blood group discrimination factor ( δθSPR ) have been studied with respect to different metal choices with their suitability to the next generation biosensor applications.

Exploration of mechanical properties of hemp fiber/flax fiber reinforced composites based on biopolymer and epoxy resin

Recently natural fiber-reinforced polymer composite materials are highly growing both in the relationship of their manufacturing industries applications such as automobile, lightweight biosensor chips, and microfluid and fundamental research as they are renewable, low, eco-friendly, biodegradable and completely recyclable. The hemp and flax solutions have not only met the technical requirements of prepared composite but also reduced environmental impacts. The present study involves the investigation on mechanical behavior such as flexural strength, flexural modulus along with moisture absorption performance of flax and hemp fiber composite is reinforced with the natural resin and epoxy resin. The biodegradable composite by the help of synthesis of natural acids such as citric acid (CA) and maleic anhydride (MA). In additional acrylic acid (AA) and glycerol (GL) were used for synthesis of natural resin to be more reactive by condensation method. The laminate has been prepared by flax and hemp fiber reinforced with the epoxy resin. The prepared laminate has been used study the flexural and tensile studies by ASTM standard procedure. The mechanical properties of flexural test and tensile test has been studied by hemp fiber/flax fiber reinforced composites. The obtain results were compared with the natural fiber reinforced by natural resin and epoxy resin. Hence, this kind of light weight biocomposite materials has been utilized for many industrial applications.

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4-6weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5-13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.

2D carbon network arranged into high-order 3D nanotube arrays on a flexible microelectrode: integration into electrochemical microbiosensor devices for cancer detection

In this work, we develop a new type of mesoporous 2D N, B, and P codoped carbon network (NBP-CNW) arranged into high-order 3D nanotube arrays (NTAs), which are wrapped onto a flexible carbon fiber microelectrode, and this microelectrode is employed as a high-performance carbon-based nanocatalyst for electrochemical biosensing. The NBP-CNW-NTAs synthesized by a facile, controllable, ecofriendly and sustainable template strategy using ionic liquids as precursors possess a high structural stability, large surface area, abundant active sites, and effective charge transport pathways, which dramatically improve their electrocatalytic activity and durability in the redox reaction of cancer biomarker H2O2. Benefiting from these unique structural merits, superb electrochemical activity and good biocompatibility, the NBP-CNW-NTAs-modified microelectrode demonstrates excellent sensing performance toward H2O2 and is embedded in a homemade microfluidic electrochemical biosensor chip for the real-time tracking of H2O2 secreted from different live cancer cells with or without radiotherapy treatment, which provides a new strategy for distinguishing the types of cancer cells and evaluating the radiotherapeutic efficacy of cancer cells. Furthermore, the functional microelectrode is integrated into an implantable probe for the in situ detection of surgically resected human specimens to distinguish cancer tissues from normal tissues. These will be of vital significance for cancer diagnoses and therapy in clinical practice.

A New Gene SCY3 Homologous to Scygonadin Showing Antibacterial Activity and a Potential Role in the Sperm Acrosome Reaction of Scylla paramamosain

In the study, a new gene homologous to the known antimicrobial peptide Scygonadin was identified in mud crab Scylla paramamosain and named SCY3. The full-length sequences of cDNA and genomic DNA were determined. Similar to Scygonadin, SCY3 was dominantly expressed in the ejaculatory ducts of male crab and the spermatheca of post-mating females at mating. The mRNA expression was significantly up-regulated after stimulation by Vibrio alginolyticus, but not by Staphylococcus aureus. The recombinant protein rSCY3 had a killing effect on Micrococcus luteus and could improve the survival rate of mud crabs infected with V. alginolyticus. Further analysis showed that rSCY3 interacted with rSCY1 or rSCY2 using Surface Plasmon Resonance (SPR, a technology for detecting interactions between biomolecules using biosensor chips) and Mammalian Two-Hybrid (M2H, a way of detecting interactions between proteins in vivo). Moreover, the rSCY3 could significantly improve the sperm acrosome reaction (AR) of S. paramamosain and the results demonstrated that the binding of rSCY3, rSCY4, and rSCY5 to progesterone was a potential factor affecting the sperm AR by SCYs on. This study lays the foundation for further investigation on the molecular mechanism of SCYs involved in both immunity and physiological effects of S. paramamosain.

Electrochemical Biosensor to Detect Implant-Derived Metal Ions: A Mice Model

Joint replacement surgeries are progressing at an increased rate in the USA, with around 1 million surgeries being performed annually. While these orthopedic implants provide a solution for a damaged joint, debris such as metal ions generated due to the wear and corrosion of the implants prove to be of considerable risk of systemic and local toxicity. As an effective diagnostic tool, there is a need to develop a patient-friendly, cost-effective, and rapid mode of metal ion detection in orthopedic patients with various implants. In this study, an electrochemical biosensor chip (Dropsens) is proposed as a diagnostic tool to detect metal ions through changes in impedance. In vivo studies were conducted using CoCrMo particles intraarticularly injected into mice. Then, blood was collected on 0th day, 14th day, and 28th day after injection and was centrifuged to obtain serum. The serum was subject to various electrochemical techniques, such as Electrochemical Impedance Spectroscopy (EIS) and cyclic voltammetry (CV). Additionally, standardization experiments were performed using different concentrations of CoCrMo wear particles suspended in PBS and mice serum. EIS results reveal a negative correlation between impedance (Rp) and the metal ion concentration in the standardization experiments. EIS and CV standardization data were used to obtain a regression equation which were later used to estimate the metal ion concentrations in experimental samples. Here, the positive control group shows the highest impedance at any frequency followed by the 28th-day experimental mice serum as seen on the bode plot. CV experimental data reveal a possible correlation between CV area and the metal ion concentrations. In this study, experimental mice models were established to mimic the possible diffusion of metal particles from implants. Dropsens electrochemical biosensors were efficiently employed to detect metal ions in serum through changes in impedance.