Biological Recognition Element Research Articles

Highly Specific Aptamer-Antibody Birecognized Sandwich Module for Ultrasensitive Detection of a Low Molecular Weight Compound.

Herein, the aptamer-antibody sandwich module was first introduced to accurately recognize a low molecular weight compound (mycotoxin). Impressively, compared with the large steric hindrance of a traditional dual-antibody module, the aptamer-antibody sandwich with low Gibbs free energy and a low dissociation constant has high recognition efficiency; thus, it could reduce false positives and false negatives caused by a dual-antibody module. As a proof of concept, a sensitive electrochemiluminescence (ECL) biosensor was constructed for detecting mycotoxin zearalenone (ZEN) based on an aptamer-antibody sandwich as a biological recognition element and porous ZnO nanosheets (Zn NSs) supported Cu nanoclusters (Cu NCs) as the signal transduction element, in which the antibody was modified on the vertex of a tetrahedral DNA nanostructure (TDN) with a rigid structure to increase the kinetics of target recognition for promoting the detection sensitivity. Moreover, the Cu NCs/Zn NSs exhibited an excellent ECL response that was attributed to the aggregation-induced ECL enhancement through electrostatic interactions. The sensing platform achieved trace detection of ZEN with a low detection limit of 0.31 fg/mL, far beyond that of the enzyme-linked immunosorbent assay (ELISA, the current rapid detection method) and high-performance liquid chromatography (HPLC, the national standard detection method). The strategy has great application potential in food analysis, environmental monitoring, and clinical diagnosis.

Importance of Biopolymers in Pharmaceutical and Medical Fields

Biopolymers have gained significant traction in the pharmaceutical and medical fields due to their unique properties and versatile applications. These naturally derived polymers exhibit remarkable characteristics such as biodegradability, biocompatibility, renewability, affordability, and availability. Their role in tissue engineering, wound healing, and biosensor development has been extensively explored. In tissue engineering, biopolymers serve as scaffolds or matrices, supporting cell growth, proliferation, and differentiation for both hard and soft tissue regeneration. Hard tissue scaffolds often incorporate biopolymers like collagen, chitosan, and gelatin, combined with bioactive ceramics like hydroxyapatite, mimicking the natural composition of bone. Soft tissue scaffolds employ biopolymers such as collagen, gelatin, elastin, and alginate, fabricated into hydrogels, fibrous meshes, or porous structures for applications like skin, vascular, cardiac, and nerve tissue regeneration. Biopolymers have demonstrated promising potential in promoting wound healing and tissue repair, creating moist wound dressings, absorbing exudates, and providing a favorable environment for tissue regeneration. Biopolymers like collagen, chitosan, and alginate have been investigated for this purpose. In biosensor development, biopolymers offer biocompatibility and the ability to immobilize biomolecules such as enzymes, antibodies, or nucleic acids, serving as matrices for biological recognition elements while maintaining their activity and stability

Biological recognition element anchored 2D graphene materials for the electrochemical detection of hazardous pollutants

The detection of hazardous pollutants in environmental and industrial settings is of critical importance for safeguarding human health and the ecosystem. Recent years witnessed significant progress and development in novel sensing platforms. The combination of biological recognition elements with two-dimensional (2D) materials enhanced the selectivity and sensitivity of pollutant detection. This review focuses on the integration of biological recognition elements, such as antibodies, nucleic acids, enzymes, aptamers, and proteins with 2D graphene for electrochemical detection of hazardous pollutants. The unique properties of graphene include high electrocatalytic activity, high surface area, and excellent conductivity, combined with the specificity and affinity of biological recognition elements, enabling selective and sensitive detection of hazardous pollutants. The synergistic coupling between 2D graphene and biological recognition elements offers several advantages, including improved sensor performance, rapid response, and potential for multi-analyte detection. Furthermore, the immobilization strategies, surface modifications, and fabrication techniques employed to anchor biological recognition elements onto graphene are discussed. The application of these bio-functionalized 2D material-based sensors for the detection of various hazardous pollutants, such as heavy metals, organic compounds, and environmental toxins, is highlighted. Moreover, the challenges and future perspectives in this field are addressed, including sensor stability, scalability, and the integration of advanced technologies, such as nanotechnology and artificial intelligence, for real-time monitoring and data analysis.

Aptamer biosensor design for the detection of endocrine-disrupting chemicals small organic molecules using novel bioinformatics methods

Endocrine-disrupting chemicals (EDCs) are substances that can disrupt the normal functioning of hormones.Using aptamers, which are biological recognition elements, biosensors can quickly and accurately detect EDCs in environmental samples. However, the elucidation of aptamer structures by conventional methods is highly challenging due to their complexity.This has led to the development of three-dimensional aptamer structures based on different models and techniques. To do this, we developed a way to predict the 3D structures of the SS DNA needed for this sequence by starting with an aptamer sequence that has biosensor properties specific to bisphenol-A (BPA), one of the chemicals found in water samples that can interfere with hormones. In addition, we will elucidate the intermolecular mechanisms and binding affinity between aptamers and endocrine disruptors using bioinformatics techniques such as molecular docking, molecular dynamics simulation, and binding energies. The outcomes of our study are to compare modeling programs and force fields to see how reliable they are and how well they agree with results found in the existing literature, to understand the intermolecular mechanisms and affinity of aptamer-based biosensors, and to find a new way to make aptamers that takes less time and costs less.

Comparative Analysis of Enzymatic and Immunological Biosensors in Biomedical Applications

Biosensors are essential for transforming biological signals into electrical ones and have a wide range of uses in the biomedical, agricultural, and environmental fields. A biosensor is a device that combines biological and physicochemical elements to detect changes in physiological or biochemical states. This paper provides a comprehensive overview of the development and application of enzymatic and immunological biosensors, emphasizing their significant role in environmental, agricultural, and biomedical sectors. By leveraging the unique properties of natural polysaccharides, particularly cellulose, for their construction, these biosensors offer enhanced biocompatibility, robust mechanical strength, and costeffectiveness. This study discusses the principles underlying biosensors, including their biological recognition elements, transduction mechanisms, and output systems. Enzymatic biosensors, characterized by their use of enzymes as bio receptors, and immunological biosensors, utilizing antibodies or antigens for the detection of immunocomplex formation, are evaluated in detail. Through comparative analysis, the paper highlights the diverse functionalities, sensitivities, and applications of these biosensors, ranging from glucose and hydrogen peroxide detection to monitoring of protein markers and E. coli bacteria. The study underscores the biosensors’ ability for facilitating rapid, incredibly sensitive, and specific detection capabilities, critical for advancing scientific diagnostics, environmental surveillance, and food protection.

Lectin-conjugated nanotags with high SERS stability: selective probes for glycans.

Surface-enhanced Raman scattering (SERS) nanotags functionalized with lectins as the biological recognition element can be used to target the carbohydrate portion of carbohydrate-carrying molecules (glycoconjugates). An investigation of the optical stability of such functionalized SERS nanotags is an essential initial step before future application and quantification of surface glycan biomarkers on cells and extracellular vesicles. Herein, we report an innovative approach to evaluate the SERS stability of lectin-conjugated nanotags by investigating any possible interfering lectin-lectin interactions in a mixture of different lectin-conjugated SERS nanotags, as well as an assessment of lectin-glycan interaction by mixing wheat germ agglutinin (WGA)-conjugated SERS nanotags with different glycoproteins. No lectin cross-reactivity was found in the mixture of lectin-conjugated SERS nanotags, evidenced by the constant SERS intensity. Additionally, the results showed that the lectins conjugated to SERS nanotags retain their ability to interact with glycans, as evidenced by the changes in the nanotag color and extinction spectra. Their SERS intensity remained constant as supported by finite-element method (FEM) simulation results, demonstrating a high SERS stability and selectivity of lectin-conjugated nanotags towards multiplex applications.

Electrochemical Biosensors Composed of Polyethylenimine (PEI) and Graphene Derivatives for Rapid Detection of Alzheimer’s Disease

Graphene materials can be used as nanofillers in polymers to take advantage of graphene's suitable properties. Graphene-PEI composites are materials that combine the unique properties of graphene and PEI. These composites are made by combining graphene with PEI through physical or chemical method. The resulting material is characterized by enhanced mechanical properties, improved electrical conductivity and increased stability. By incorporating graphene into biosensor platforms, it can improve overall’s performance, including sensitivity, specificity and response. In this work, the detection of anti-βA40 biomarker was tested. Beta-amyloid peptide (βA1-40) was incorporated into liposomes of Dipalmitoyl Phosphatidylglycerol (DPPG) and was immobilized using Layer-by-Layer self-assembling technique on PEI_graphene derivatives composites. To obtain these composites it was utilized graphene oxide (GO) from Hummers’ method, it’s thermally reduced form (rGO) and also electrochemically exfoliated graphene (EEG). MilliQ water was added to the PEI to obtain a concentration of 2mg/mL and stirred for 30 min at room temperature for complete dissolution of the PEI. Then EEG, GO and rGO were added to PEI solution and subjected to ultrasonication in a Hielscher UP400ST sonicator, using the H14 probe for 30 minutes to obtain a homogeneous and stable dispersion.Carbon microelectrodes modified with PEI-graphene derivatives composites and (DPPG +Aβ-40) were used as biosensors platforms to detect anti-Aβ40 related to Alzheimer's disease. The assembly of the biosensors is shown in Figure 1. Cyclic Voltammetry was performed in three cycles, at a potential of -0.6 V to 0.6 V and scan rate of 0.05 V s-1 to evaluate the sensory response. The electrochemical measurements were performed with saline phosphate buffer solution (PBS). The morphology of PEI and PEI_graphene oxide can be seen in Figure 2. The large surface area of graphene allows for increased binding sites for bioreceptors, which may favor the adsorption of Aβ-40 peptide, improving signal transduction and sensitivity of the biosensor. The wettability of the composites was obtained through measurements of the static contact angle using the Ramé-Hart Contact Angle Goniometer (model 100-25-A). Figure 3 presents the contact angle for a film layer of the composites. All PEI_graphene derivative composites showed hydrophilic behavior (θ < 90°), PEI_EEG composite stood out as less hydrophilic (θ = 68°) among all composites. Hydrophilicity is essential in biosensors because it affects the interactions between the biological recognition elements and the target analytes, as well as the overall stability and reliability of the biosensor. Figure 4 presents the calibration curves using the normalized area obtained from cyclic voltammetry of the biosensors manufactured with 2 bilayers (PEI_graphene derivative/DPPG+Aβ40) and anti-Aβ40 biomarker in concentrations ranging from 1 ng mL to 5 µg mL-1. Among the tested PEI_graphene derivatives composites, the ones with EEG and RGO stood out in relation to pure PEI. Table 1 presents the adjusted R-square of the data in Figure 4. All composites, except PEI_GO, showed excellent linear fit, adjusted R-square close to 1 in the detection range between 1 and 1000 ng mL-1. The PEI_graphene oxide composite can be used in biosensors to enable rapid and efficient transduction of the binding signal, leading to improved detection performance. Figure 1

(Invited) Real Time Monitoring of Target Binding for the Development of Clinical Diagnostic Tests

Currently, there is tremendous interest in developing continuous monitoring systems for better managing health and disease. These platforms rely on readout methods that continuously monitor the presence of bioanalytes in physiological matrices. In this talk, I will discuss the development of new electrochemical signal readout methods that continuously monitor the binding of targets with biological recognition elements such as functional nucleic acids. We will discuss the application of these platforms to the detection of infectious pathogens as a model system, but will show the possibility of its extension to protein targets.

Reports on the sensitivity enhancement in interferometric based biosensors by biotin-streptavidin system

Antibody biotinylation is a process of attaching biotin molecules to antibodies by chemically modifying specific functional groups on the antibodies without altering their antigen recognition specificity. Biotin, a small vitamin, forms a strong and specific interaction with the protein streptavidin, resulting in a stable biotin-streptavidin (biotin-STV) complex. This biotin-STV interaction is widely exploited in various biotechnological applications, including biosensors. Biosensors are analytical devices that employ biological recognition elements, such as antibodies, enzymes, or nucleic acids, to detect and quantify target analytes in a sample. Antibodies are commonly used as recognition elements in biosensors due to their high specificity and affinity. In this study, the antibody anti-Bovine Serum Albumin (αBSA) has been biotinylated at different antibody:biotin ratios, and the stability of this labeling over time has been investigated. Furthermore, the sensitivity of the biosensor for detecting the Bovine Serum Albumin (BSA) protein has been compared using the biotinylated antibody and the non-biotinylated form, showing a four-fold improvement in detection. This system was also compared with the Enzyme-Linked ImmunoSorbent Assay (ELISA) technique. The advantages of using biotinylated antibodies in biosensors include increased stability and reproducibility of the biorecognition layer, as well as flexibility in sensor design, as different biotinylated antibodies can be utilized for diverse target analytes without altering the sensor's architecture.

Advancements in wearable technology for monitoring lactate levels using lactate oxidase enzyme and free enzyme as analytical approaches: A review

Lactate is a metabolite that holds significant importance in human healthcare, biotechnology, and the food industry. The need for lactate monitoring has led to the development of various devices for measuring lactate concentration. Traditional laboratory methods, which involve extracting blood samples through invasive techniques such as needles, are costly, time-consuming, and require in-person sampling. To overcome these limitations, new technologies for lactate monitoring have emerged. Wearable biosensors are a promising approach that offers non-invasiveness, low cost, and short response times. They can be easily attached to the skin and provide continuous monitoring. In this review, we evaluate different types of wearable biosensors for lactate monitoring using lactate oxidase enzyme as biological recognition element and free enzyme systems.

Application and progress of electrochemical biosensors for the detection of pathogenic viruses

Viruses, with high fatality rates, have posed significant threat to global public health recent decades, necessitating rapid and accurate diagnostic methods to cut off their transmission effectively. To meet with this ongoing demand, electrochemical biosensors have emerged as powerful tools for virus detection due to their high sensitivity, good selectivity, cost-effectiveness, and rapid response. In this review, the fundamental components in the design of electrochemical biosensors, including biological recognition elements, nanomaterials, and signal outputs are introduced and their respective advantages and limitations are discussed. Furthermore, the employment of emerging innovative techniques, such as electrochemical collision technique and artificial intelligence technology and their combination with electrochemical biosensors for virus detection are discussed, which will provide valuable insights into the future prospects of electrochemical biosensors in virus detection.

Molecularly imprinted polymer hydrogel sheets with metalloporphyrin-incorporated molecular recognition sites for protein capture

Metalloporphyrins are often found in nature as coordination recognition sites within biological process, and synthetically offer the potential for use in therapeutic, catalytic and diagnostic applications. While porphyrin containing biological recognition elements have stability limitations, molecularly imprinted polymers bearing these structures offer an alternative with excellent robustness and the ability to work in extreme conditions. In this work, we synthesised a polymerizable porphyrin and metalloporphyrin and have incorporated these as co-monomers within a hydrogel thin-sheet MIP for the specific recognition of bovine haemoglobin (BHb). The hydrogels were evaluated using Scatchard analysis, with Kd values of 10.13 × 10−7, 5.30 × 10−7, and 3.40 × 10−7 M, for the control MIP, porphyrin incorporated MIP and the iron-porphyrin incorporated MIP, respectively. The MIPs also observed good selectivity towards the target protein with 73.8%, 77.4%, and 81.2% rebinding of the BHb target for the control MIP, porphyrin incorporated MIP and the iron-porphyrin incorporated MIP, respectively, compared with the non-imprinted (NIP) counterparts. Specificity was determined against a non-target protein, Bovine Serum Albumin (BSA). The results indicate that the introduction of the metalloporphyrin as a functional co-monomer is significantly beneficial to the recognition of a MIP, further enhancing MIP capabilities at targeting proteins.

Phage-Based Biosensing for Rapid and Specific Detection of Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a major foodborne pathogen. Rapid and specific detection is crucial for controlling staphylococcal food poisoning. This study reported a Staphylococcus phage named LSA2302 showing great potential for applications in the rapid detection of S. aureus. Its biological characteristics were identified, including growth properties and stability under different pH and temperature conditions. The genomic analysis revealed that the phage has no genes associated with pathogenicity or drug resistance. Then, the phage-functionalized magnetic beads (pMB), serving as a biological recognition element, were integrated with ATP bioluminescence assays to establish a biosensing method for S. aureus detection. The pMB enrichment brought high specificity and a tenfold increase in analytical sensitivity during detection. The whole detection process could be completed within 30 min, with a broad linear range of 1 × 104 to 1 × 108 CFU/mL and a limit of detection (LOD) of 2.43 × 103 CFU/mL. After a 2 h pre-cultivation, this method is capable of detecting bacteria as low as 1 CFU/mL. The recoveries of S. aureus in spiked skim milk and chicken samples were 81.07% to 99.17% and 86.98% to 104.62%, respectively. Our results indicated that phage-based biosensing can contribute to the detection of target pathogens in foods.

Current Trends in the Use of Semiconducting Materials for Electrochemical Aptasensing

Aptamers are synthetic single-stranded oligonucleotides that exhibit selective binding properties to specific targets, thereby providing a powerful basis for the development of selective and sensitive (bio)chemical assays. Electrochemical biosensors utilizing aptamers as biological recognition elements, namely aptasensors, are at the forefront of current research. They exploit the combination of the unique properties of aptamers with the advantages of electrochemical detection with the view to fabricate inexpensive and portable analytical platforms for rapid detection in point-of-care (POC) applications or for on-site monitoring. The immobilization of aptamers on suitable substrates is of paramount importance in order to preserve their functionality and optimize the sensors’ sensitivity. This work describes different immobilization strategies for aptamers on the surface of semiconductor-based working electrodes, including metal oxides, conductive polymers, and carbon allotropes. These are presented as platforms with tunable band gaps and various surface morphologies for the preparation of low cost, highly versatile aptasensor devices in analytical chemistry. A survey of the current literature is provided, discussing each analytical method. Future trends are outlined which envisage aptamer-based biosensing using semiconductors.

Smartphone-Based Electrochemical Biosensor for On-Site Nutritional Quality Assessment of Coffee Blends.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess a coffee blend's total polyphenols (Phs) content at the industrial and individual levels. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biological recognition element, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as a cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat, the Sensit Smart by PalmSens, connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 μA/μM, a linear response ranging from 5 to 70 μM, and a lower detection limit (LOD) of 2.99 μM. Afterward, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor's performance was validated through the Folin-Ciocâlteu standard method.

Gemcitabine drug intercalation with ds-DNA at surface of ds-DNA/Pt–ZnO/SWCNTs/GCE biosensor: A DNA-biosensor for gemcitabine monitoring confirmed by molecular docking study

Herein, a facile and highly sensitive electroanalytical tool for monitoring and quantifying the antineoplastic drug gemcitabine in real sample was provided. In this regard, a novel DNA-biosensor based on Pt-doped ZnO decorated single walled carbon nanotubes (Pt–ZnO/SWCNTs) hybrid nanomaterial modification of glassy carbon electrode (GCE) was fabricated. Ds-DNA (Calf Thymus), as a biological recognition element, was decorated onto nanomaterial-modified GCE via layer-by-layer fabrication strategy to attain ultimate biosensor ds-DNA/Pt–ZnO/SWCNTs/GCE. The characterizations confirmed the successful fabrication of hybrid nanomaterial, as well as the modification of electrode surface by fabricated nanomaterial. The electrochemical impedance spectroscopy (EIS) analysis revealed that the nanomaterial modification of GCE surface enhanced the electrical conductivity thanks to the synergistic effects of Pt–ZnO and SWCNTs structures, thereby boosted the electrocatalytic activity of the resultant biosensor. The electrochemical characterization results showed that the suggested biosensor is capable of detecting gemcitabine in a wide concentration range of 0.01–30.0 μM, with a detection limit of 5.0 nM. The intercalation binding mode of Gemcitabine inside guanine and cytosine rich region of DNA receptor was approved by molecular docking study. The results of the experimental data were well congruent with the molecular docking analysis, which showed that the binding mode of gemcitabine drug with ds-DNA was intercalation.

Biofunctionalized Silicon Carbide-Titanium (SiC-Ti) Platforms for the Determination of Enteropathogenic Escherichia coli by an Infrared Biosensor

Escherichia coli (E. coli) may be harmful to humans. Hence, a rapid, low cost, and easy detection method is needed, and optical biosensors are an excellent option. Here a new platform based upon silicon carbide and titanium (SiC-Ti) was used to determine enteropathogenic E. coli by Fourier transform infrared (FTIR) spectroscopy. Self-assembly monolayer (SAM) approach was used to modify the platform. Antibody anti-E. coli flagella were obtained and utilized as the biological recognition element. Three concentrations of bacteria (10, 100, and 1000 CFU/mL) were determined. The detection region was from 1330 to 1480 cm−1, where characteristic bands associated with E. coli were determined. An increase in the absorption intensity was observed with the bacteria concentration, demonstrating suitability for quantitative analysis.

The designation, synthesis, and affinity determination of affinity peptide for anthrax protective antigen.

Detection of anthrax protective antigen is an effective way to diagnose anthracnose, and it plays an important part in the treatment of anthracnose. Affinity peptides, as a miniature biological recognition element, can quickly and effectively detect anthrax protective antigens. Based on computer-aided design technology (CAD), we have herein developed an affinity peptide design strategy for the detection of anthrax protective antigens. Firstly, six high-value mutation sites were determined based on the molecular docking between the template peptide and the receptor, and then the multi-site mutation of amino acids was carried out in order to establish a virtual peptide library. The library was selected by using molecular dynamics simulation and the best designed affinity peptide (code: P24) was found. The theoretical affinity with P24 peptide has increased by 19.8% compared with template peptide. Finally, the affinity with P24 peptide was measured by SPR technology to reach the nanomole level, which verified the effectiveness of the design strategy. The newly designed affinity peptide is expected to be used in the diagnosis of anthracnose.

Electrochemical aptasensors for pathogenic detection toward point-of-care diagnostics.

A biosensor system refers to a biomedical device, which detects biological, chemical, or biochemical components by converting those signals to an electrical signal by utilizing and uniting physical or chemical transducer with biorecognition elements. An electrochemical biosensor is generally based on the reaction of either production or consumption of electrons under a three-electrode system. Biosensor systems are exploited in a wide range of areas, such as medicine, agriculture, husbandry, food, industry, environment protection, quality control, waste disposal, and the military. Pathogenic infections are the third leading cause of death worldwide after cardiovascular diseases and cancer. Therefore, there is an urgent need for effective diagnostic tools to control food, water, and soil contamination result in protecting human life and health. Aptamers are peptide or oligonucleotide-based molecules that show very high affinity to their targets that are produced from large pools of random amino acid or oligonucleotide sequences. Generally, aptamers have been utilized for fundamental sciences and clinical implementations for their target-specific affinity and have been intensely exploited for different kinds of biosensor applications for approximately 30 years. The convergence of aptamers with biosensor systems enabled the construction of voltammetric, amperometric, and impedimetric biosensors for the detection of specific pathogens. In this review, electrochemical aptamer biosensors were evaluated by discussing the definition, types, and production techniques of aptamers, the advantages of aptamers as a biological recognition element against their alternatives, and a wide range of aptasensor examples from literature in the detection of specific pathogens.

Hybrid Supported Lipid Bilayers for Bioinspired Bioelectronics with Enhanced Stability

A promising new class of biosensors leverages the sensing mechanisms of living cells by incorporating native transmembrane proteins into biomimetic membranes. Conducting polymers (CPs) can further improve the detection of electrochemical signals from these biological recognition elements through their low electrical impedance. Supported lipid bilayers (SLBs) on CPs mimic the structure and biology of the cell membrane to enable such sensing, but their extrapolation to new target analytes and healthcare applications has been difficult due to their poor stability and limited membrane properties. Blending native phospholipids with synthetic block copolymers to create a hybrid SLB (HSLB) may address these challenges by allowing for the tuning of chemical and physical properties during membrane design. We establish the first example of HSLBs on a CP device and show that polymer incorporation enhances bilayer resilience and thus offers important benefits toward bio-hybrid bioelectronics for sensing applications. Importantly, HSLBs outperform traditional phospholipid bilayers in stability by exhibiting strong electrical sealing after exposure to physiologically relevant enzymes that cause phospholipid hydrolysis and membrane degradation. We investigate the impact of HSLB composition on membranes and device performance and demonstrate the ability to finely adjust the lateral diffusivity of HSLBs with modest changes in block copolymer content through a large compositional range. The inclusion of the block copolymer into the bilayer does not disrupt electrical sealing on CP electrodes, an essential metric for electrochemical sensors, or the insertion of a representative transmembrane protein. This work interfacing tunable and stable HSLBs with CPs paves the way for future bioinspired sensors that combine the exciting developments from both bioelectronics and synthetic biology.