Multifunctional Biosensor Research Articles

A multifunctional flexible biosensor for the non-destructive detection and sterilization of Staphylococcus aureus

The early diagnosis of bacterial contamination is critical in safeguarding the food supply chain and public health. Although substantial efforts have been undertaken to identify and quantify foodborne bacteria, most of them require destructive sample pretreatment, limiting their utility in on-site diagnosing of bacterial contamination. Here, a novel multifunctional paper-based electrochemiluminescence (ECL) biosensor was designed for the efficient capture, elimination, and ultrasensitive detection of Staphylococcus aureus (S. aureus). Vancomycin functionalized Pt nanoparticles (Van@Pt NPs) were labeled on the recognition probe (aptamer) and subsequently fixed on paper substrate which could selectively capture target bacteria and allow the total annihilation in 1.5 h. After recognizing S. aureus, the reminder Van@Pt NPs on paper was monitored by Zn-MOFs:Au NPs/ITO electrode due to their excellent quenching effect on the ECL signal of Zn-MOFs:Au NPs. Under optimal conditions, the sensor exhibited a good linear relationship in a range of 5–108 CFU/mL and a low detection limit of 1 CFU/mL for S. aureus. Moreover, this way possessed good precision for the non-destructive evaluation of S. aureus-contaminated sample compared with the gold-standard method. This portable and multi-functional biosensor held great promise for applications in non-destructive and real-time bacterial contamination and treatment.

A portable multifunctional biosensor based on a newly screened endogenous reference gene for pork adulteration detection

The adulteration of animal-derived food is a widespread problem with meat adulteration emerging as a global concern. To address the need for on-site rapid detection and visual analysis, a portable multifunction biosensor (PMB) was developed. This device integrates Recombinase Polymerase Amplification (RPA), CRISPR/Cas12a assay, and a custom-designed 3D-printed multifunction device, specifically for the visual and rapid detection of pork in food. Initially, a screening model was constructed using Perl bioinformatics based on chromosomal gene information, and the LOC110262058 gene was selected as a reliable endogenous reference gene for pigs. Subsequently, a one-tube RPA-CRISPR/Cas12a system was established to simplify the procedures, converting pork-specific signals into fluorescence while preventing cross-contamination. In addition, an independently designed 3D-printed multifunction device was developed to support the RPA-CRISPR/Cas12a system for one-tube detection, incorporating functions such as heating, centrifugation, and imaging. The reaction conditions of the PMB were optimized to reduce the reaction time to 20–30 min with a sensitivity of 0.01 g/100 g. The analysis of actual samples indicated that the PMB has high selectivity and practical effectiveness for pork detection. The proposed biosensor offers several detection advantages, including output, ease of use, stability, and independence from complex equipment, making it a powerful method for rapid pork detection in food.

Apt-Conjugated PDMS-ZnO/Ag-Based Multifunctional Integrated Superhydrophobic Biosensor with High SERS Activity and Photocatalytic Sterilization Performance.

Sensitive detection and efficient inactivation of pathogenic bacteria are crucial for halting the spread and reproduction of foodborne pathogenic bacteria. Herein, a novel Apt-modified PDMS-ZnO/Ag multifunctional biosensor has been developed for high-sensitivity surface-enhanced Raman scattering (SERS) detection along with photocatalytic sterilization towards Salmonella typhimurium (S. typhimurium). The distribution of the electric field in PDMS-ZnO/Ag with different Ag sputtering times was analyzed using a finite-difference time-domain (FDTD) algorithm. Due to the combined effect of electromagnetic enhancement and chemical enhancement, PDMS-ZnO/Ag exhibited outstanding SERS sensitivity. The limit of detection (LOD) for 4-MBA on the optimal SERS substrate (PZA-40) could be as little as 10-9 M. After PZA-40 was modified with the aptamer, the LOD of the PZA-40-Apt biosensor for detecting S. typhimurium was only 10 cfu/mL. Additionally, the PZA-40-Apt biosensor could effectively inactivate S. typhimurium under visible light irradiation within 10 min, with a bacterial lethality rate (Lb) of up to 97%. In particular, the PZA-40-Apt biosensor could identify S. typhimurium in food samples in addition to having minimal cytotoxicity and powerful biocompatibility. This work provides a multifunctional nanoplatform with broad prospects for selective SERS detection and photocatalytic sterilization of pathogenic bacteria.

Bridging biological and food monitoring: A colorimetric and fluorescent dual-mode sensor based on N-doped carbon dots for detection of pH and histamine

Rapid and sensitive monitoring of pH and histamine is crucial for bridging biological and food systems and identifying corresponding abnormal situations. Herein, N-doped carbon dots (CDs) are fabricated by a hydrothermal method employing dipicolinic acid and o-phenylenediamine as precursors. The CDs exhibit colorimetric and fluorescent dual-mode responses to track pH and histamine variations in living cells and food freshness, respectively. The aggregation-induced emission enhancement and intramolecular charge transfer result in a decrease in absorbance and an increase in fluorescence, which become readily apparent as the pH changes from acidic to neutral. This property enables precise differentiation between normal and cancerous cells. Furthermore, given the intrinsic basicity of histamine, pH-responsive CDs are advantageous for additional colorimetric and fluorescent monitoring of histamine in food freshness, achieving linearities of 25–1000 µM and 30–1000 µM, respectively, which are broader than those of alternative nanoprobes. Interestingly, the smartphone-integrated sensing platform can portably and visually evaluate pH and histamine changes due to sensitive color changes. Therefore, the sensor not only establishes a dynamic connection between pH and histamine for the purposes of biological and food monitoring, but also presents a novel approach for developing a multifunctional biosensor that can accomplish environmental monitoring and biosensing simultaneously.

A Multifunctional Biosensor via MXene Assisted by Conductive Metal–Organic Framework for Healthcare Monitoring

AbstractFor real‐time care of metabolic diseases, it is highly demanded to simultaneously monitor metabolite content and diagnose muscle strength in a rapid and convenient way. However, such a biosensor with integrated functions of detecting chemical and biopotential signals at the same time has seldom been reported. In this work, a multifunctional biosensor, integrating the electrochemical detection of uric acid (UA) and glucose (Glu) in sweat, electrophysiological signal acquisition, and electrostimulation therapy, is designed. Hence, an electrophysiological MOF/MXene electrode is fabricated using highly conductive MXene and porous conductive metal–organic framework (c‐MOF, Ni3(HITP)2). Compared with commercial Ag/AgCl electrode, MOF/MXene electrode has lower electrode/skin interface impedance, higher stability and signal‐to‐noise (SNR). By utilizing the high charge storage capacity (CSC) of MOF/MXene electrode, it can realize muscle treatment by electrostimulation. Besides, with abundant active regions of c‐MOF, the electrode exhibits excellent electrochemical performance in detecting sweat metabolites. Multimodal signals detected by such integrated biosensors are wirelessly transmitted to a mobile terminal, showing significant potential on muscle theranostics and daily non‐invasive monitoring. Additionally, they offer timely nutritional guidance for individuals dealing with hyperuricemia or hyperglycemia.

A Multi-Functional CMOS Biosensor Array With On-Chip DEP-Assisted Sensing for Rapid Low-Concentration Analyte Detection and Close-Loop Particle Manipulation With No External Electrodes.

This article presents a fully-integrated dielectrophoresis (DEP)-assisted multi-functional CMOS biosensor array chip with 4096 working electrodes (WEs), 12288 photodiodes (PDs), reference electrodes (REs), and counter electrodes (CEs), while each WE and photodiode can be reconfigured to support on-chip DEP actuation, electrochemical potentiostat, optical shadow imaging, and complex impedance sensing. The proposed CMOS biosensor is an example of an actuation-assisted label-free biosensor for the rapid sensing of low-concentration analytes. The DEP actuator of the proposed CMOS biosensor does not require any external electrode. Instead, on-chip WE pairs can be re-used for DEP actuation to simplify the sensor array design. The CMOS biosensor is implemented in a standard 130-nm BiCMOS process. Theoretical analyses and finite element method (FEM) simulations of the on-chip DEP operations are conducted as proof of concept. Biological assay measurements (DEP actuation/electrochemical potentiostat/impedance sensing) with E.coli bacteria and microbeads (optical shadow imaging) demonstrate rapid detection of low-concentration analytes and simultaneous manipulation and detection of large particles. The on-chip DEP operations draw the analytes closer to the sensor electrode surface, which overcomes the diffusion limit and accelerates low-concentration analyte sensing. Moreover, the DEP-based movement of large particles can be readily detected by on-chip photodiode arrays to achieve close-loop manipulation and sensing of particles and droplets. These show the unique advantages of the DEP-assisted multi-functional biosensor.

Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the life expectancy of patients with NSCLC, concerns about TKI-induced cardiotoxicities have increased. AC0010, a novel third-generation TKI, was developed to overcome drug resistance induced by EGFR-T790M mutation. However, the cardiotoxicity of AC0010 remains unclear. To evaluate the efficacy and cardiotoxicity of AC0010, we designed a novel multifunctional biosensor by integrating microelectrodes (MEs) and interdigital electrodes (IDEs) to comprehensively evaluate cell viability, electrophysiological activity, and morphological changes (beating of cardiomyocytes). The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative, label-free, noninvasive, and real-time manner. AC0010 was found to significantly inhibit NCI-H1975 (EGFR-L858R/T790M mutation), while weak inhibition was found for A549 (wild-type EGFR). Negligible inhibition was found in the viabilities of HFF-1 (normal fibroblasts) and cardiomyocytes. With the multifunctional biosensor, we found that 10 μM AC0010 significantly affected the extracellular field potential (EFP) and mechanical beating of cardiomyocytes. The amplitude of EFP continuously decreased after AC0010 treatment, while the interval decreased first and then increased. We analyzed the change in the systole time (ST) and diastole time (DT) within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment. This result probably indicated that the relaxation of cardiomyocytes was insufficient, which may further aggravate the dysfunction. Here, we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations (10 μM). This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated. In addition, novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.

Multiarray Biosensor for Diagnosing Lung Cancer Based on Gap Plasmonic Color Films.

Adaptable and sensitive materials are essential for the development of advanced sensor systems such as bio and chemical sensors. Biomaterials can be used to develop multifunctional biosensor applications using genetic engineering. In particular, a plasmonic sensor system using a coupled film nanostructure with tunable gap sizes is a potential candidate in optical sensors because of its simple fabrication, stability, extensive tuning range, and sensitivity to small changes. Although this system has shown a good ability to eliminate humidity as an interferant, its performance in real-world environments is limited by low selectivity. To overcome these issues, we demonstrated the rapid response of gap plasmonic color sensors by utilizing metal nanostructures combined with genetically engineered M13 bacteriophages to detect volatile organic compounds (VOCs) and diagnose lung cancer from breath samples. The M13 bacteriophage was chosen as a recognition element because the structural protein capsid can readily be modified to target the desired analyte. Consequently, the VOCs from various functional groups were distinguished by using a multiarray biosensor based on a gap plasmonic color film observed by hierarchical cluster analysis. Furthermore, the lung cancer breath samples collected from 70 healthy participants and 50 lung cancer patients were successfully classified with a high rate of over 89% through supporting machine learning analysis.

Anhydrobiotic chironomid larval motion-based multi-sensing microdevice for the exploration of survivable locations

SummaryAfrican chironomid (Polypedilum vanderplanki) larvae can suspend their metabolism by undergoing severe desiccation and then resume this activity by simple rehydration. We present a microdevice using interdigital comb electrodes to detect the larval motion using the natural surface charge of the living larvae in water. The larvae were most active 2 h after soaking them in water at 30°C; they exhibited motions with 2 Hz frequency. This was comparable to the signal obtained from the microdevice via fast Fourier transform (FFT) processing. The amplitude of the voltage and current were 0.11 mV and 730 nA, respectively. They would be enough to be detected by a low power consumption microcomputer. Temperature and pH sensing were demonstrated by detecting the vital motions of the revived larvae under different conditions. This multi-functional biosensor will be a useful microdevice to search for survivable locations under extreme environmental conditions like those on other planets.

Recent Advances of Biosensors Based on Split Aptamers in Biological Analysis: A Review

Aptamers are oligonucleotides with distinct conformational shapes that allow them to bind a wide range of targets with high affinity and specificity. Compared with intact parent aptamers, split aptamers show advantages of small size and less unfavorable secondary structures, thus avoiding high background, false positive or non-specific signals well. Moreover, they are favorable to design label-free strategies since some fluorescent dyes are known to intercalate into DNA structure rather than covalent conjugation. So far, split aptamer fragments have shown good application prospects in the development of various high-performance biosensors. In this review, recent advances of biosensors based on split aptamers in biological analysis are summarized and elucidated. It includes the detection of nucleotides/nucleosides, alkaloids, proteins, antibiotics, exosomes, and tumor cells. Potential general platforms for the assay of more than one targets based on multifunctional biosensor are also included. Challenges and prospects for future development are discussed to provide valuable insights for the research of new split aptamers and aptasensors for more targets analysis.

Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies.

Imbalances in levels of glutamate (GLU) and gamma-aminobutyric acid (GABA) and their sub-second signaling dynamics occur in several brain disorders including traumatic brain injury, epilepsy, and Alzheimer’s disease. The present work reports on the optimization and in vivo testing of a silicon (Si) multifunctional biosensor probe for sub-second simultaneous real-time detection of GLU and GABA. The Si probe features four surface-functionalized platinum ultramicroelectrodes (UMEs) for detection of GLU and GABA, a sentinel site, and integrated microfluidics for in-situ calibration. Optimal enzyme concentrations, size-exclusion phenylenediamine layer and micro spotting conditions were systematically investigated. The measured GLU sensitivity for the GLU and GABA sites were as high as 219 ± 8 nA μM−1 cm−2 (n = 3). The measured GABA sensitivity was as high as 10 ± 1 nA μM−1 cm−2 (n = 3). Baseline recordings (n = 18) in live rats demonstrated a useful probe life of at least 11 days with GLU and GABA concentrations changing at the levels of 100′s and 1000′s of μM and with expected periodic bursts or fluctuations during walking, teeth grinding and other activities and with a clear difference in the peak amplitude of the sensor fluctuations between rest (low) and activity (higher), or when the rat was surprised (a reaction with no movement). Importantly, the probe could improve methods for large-scale monitoring of neurochemical activity and network function in disease and injury, in live rodent brain.

Numerical Analysis of Multifunctional Biosensor with Dual-Channel Photonic Crystal Fibers Based on Localized Surface Plasmon Resonance

A multifunctional biosensor composed of a dual-channel photonic crystal fiber (PCF) based on localized surface plasmon resonance (LSPR) is presented to measure dynamic changes in the magnetic field, temperature, and analyte refractive index at mid-infrared wavelengths. The finite-element method (FEM) is used to model and determine the sensing properties of the sensor. The flat dual-channel surface is coated with a gold film, and two nanowires are put on the fan-shaped openings to create directional resonance coupling to detect the analyte refractive index and temperature. By utilizing that the refractive index (RI) of the filled magnetic fluid (MF) is sensitive to the external magnetic field and temperature, a sensor with multi-physical detection functions is obtained. For refractive indexes ranging from 1.47 to 1.52, the maximum sensitivity is as high as 31,000 nm/RIU, with a resolution of 3.22 × 10−6 RIU. The maximum sensitivities for the magnetic field and temperature are 1970 pm/Oe and −5500 pm/°C, respectively.

Multifunctional biosensor constructed by Ag-coating magnetic-assisted unique urchin core porous shell structure for dual SERS enhancement, enrichment, and quantitative detection of multi-components inflammatory markers

The simultaneous, precise, and quantitative detection of multi-components inflammatory markers (IMs) in sepsis serum by surface-enhanced Raman scattering (SERS) remains a challenging problem. A novel, multifunctional biosensor with dual enrichment and enhancement was designed for the ultrasensitive and quantitative analysis of multi-components IMs. The biosensor contains SERS tags-unique urchin core/porous shell (CPS) structure modified with Raman reporters (RaRs), magnetic assist-Ag coated Fe3O4 magnetic nanoparticles (Ag MNPs) modified with internal standard (IS), and then aptamer (Apt) modification to form the sandwich structure (Ag MNPs/IMs/CPS). This multifunctional sensor used for IMS detection has the following innovations: The intensity ratio IRaRs/IIS with Lg CIMs present a good and wide linear relationship to achieve the simultaneous, precise, and quantitative detection of IMS in serum; The detection results display ultrasensitivity, and the limit of detection (LOD) for CRP, IL-6, and PCT is 100 fg/mL, 0.1 fg/mL, and 1.0 fg/mL, which is lower than other detection techniques; The calculated data of clinical blood samples of sepsis by this SERS method is consistent with the hospital results, and can provide more compositional data of IMs. Thus, this combined approach developed a sensing platform for rapid screening, accurate evaluation, early warning, and diagnosis of sepsis.

Highly Sensitive Multi-Functional Plasmonic Biosensor Based on Dual Core Photonic Crystal Fiber

In this paper, highly efficient multi-functional biosensor based on surface plasmon resonance (SPR) is proposed and analyzed. The suggested sensor has a dual core PCF infiltrated with temperature dependent alcohol mixture. In addition, two gold nanorods are mounted vertically at the inner surface of the central PCF hole that is infiltrated with the studied analyte. Through the proposed biosensor, both analyte refractive index (RI) and temperature can be detected. The geometrical parameters of the reported structure are studied to maximize the sensitivity. Full vectorial finite element method (FVFEM) is utilized throughout the numerical analysis of the reported structures. The reported multi-functional biosensor achieves high temperature sensitivity of 21.05 nm/°c and very high refractive index sensitivity of 34600 nm/RIU. The achieved RI and temperature sensitivities are higher than the recent reported sensors in the same wavelength and temperature ranges.

Multifunctional Biosensor with Dual-Channel Photonic Crystal Fibers Based on Localized Surface Plasmon Resonance

Multifunctional Biosensor with Dual-Channel Photonic Crystal Fibers Based on Localized Surface Plasmon Resonance

One-pot synthesis to prepare lignin/photoacid nanohybrids for multifunctional biosensors and photo-triggered singlet oxygen generation

This study presents a one-pot synthesis approach for a sustainable lignin/photoacid nanohybrid multifunctional biosensor (AL-Por-PP) for fluorescent live cell imaging, bisulfite detection and photo-trigger singlet oxygen generation.

Brain-implantable multifunctional probe for simultaneous detection of glutamate and GABA neurotransmitters

Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA μM -1 cm -2 and maximum sensitivities of 204±15 nA μM -1 cm -2 and 37±7 nA μM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2, GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

A facile SERS strategy to detect glucose utilizing tandem enzyme activities of Au@Ag nanoparticles

Surface-Enhanced Raman Scattering (SERS) is a powerful analysis technology, attracting more and more attention due to its high sensitivity and selectivity. Herein, we report a simple seed-mediated method to synthesize Au@Ag nanoparticles (NPs) as a multifunctional biosensor for the label-free detection of hydrogen peroxide (H2O2) and glucose by SERS. Au@Ag NPs, as an ultrasensitive SERS substrate, show the dual activities (peroxidase-like and GOx-like activities). Under the condition of pH 4.0 NaAc buffer solution, the glucose and H2O can be catalyzed by Au@Ag NPs to produce glucose acid and H2O2, and then H2O2 can oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to form a blue oxidation product oxidic TMB (oxTMB) which exhibits strong SERS signals at 1188, 1330, 1605 cm−1. Thus, we have developed a new SERS strategy for analysis of glucose with a detection limit of 5 × 10−10molL−1, suggesting that Au@Ag NPs have the potential for biosensor, immunoassay and medical treatment.

Enhancing plasmonic effect in periodic nanometal square prisms with fences and cavities for refractive index and temperature sensing applications

This paper investigates the enhancing plasmonic effect of periodic arrays of silver-shell square prisms employing a three-dimensional finite element method for refractive index and temperature sensing applications in the near-infrared region. We found that the connected metal-shell square prisms could simultaneously generate surface, gap, and cavity plasmon resonances modes in a single structure and remarkably enhance the sensing performance. The proposed design, constructed using silver-shell square prisms with linked fences, as a plasmon resonance source in the center of the unit cell, can sense refractive index and temperature with outstanding sensitivity as 940 nm/RIU and 0.5 nm/°C, respectively. Simulation results reveal that the proposed structure’s absorptance is approximately perfect, significantly larger than its concrete counterpart without the center cavity and linked fences. The proposed system has a strong dipolar effect generated from the mutual inductance on metal and coupled fences, and the capacitive coupling in cavity regions of nanostructures. These distinctive advantages enable the linkage-based plasmonic sensor, a multi-functional biosensor, and a potential label-free photonic device.

Bacterial flagellar motor as a multimodal biosensor.

Bacterial Flagellar Motor is one of nature's rare rotary molecular machines. It enables bacterial swimming and it is the key part of the bacterial chemotactic network, one of the best studied chemical signalling networks in biology, which enables bacteria to direct its movement in accordance with the chemical environment. The network can sense down to nanomolar concentrations of specific chemicals on the time scale of seconds. Motor's rotational speed is linearly proportional to the electrochemical gradients of either proton or sodium driving ions, while its direction is regulated by the chemotactic network. Recently, it has been discovered that motor is also a mechanosensor. Given these properties, we discuss the motor's potential to serve as a multifunctional biosensor and a tool for characterising and studying the external environment, the bacterial physiology itself and single molecular motor biophysics.