Uniformity is a key parameter to assure the accuracy of biosensor devices. In this work, highly uniform carbon nanotube thin-film transistors (CNT-TFTs) with a standard deviation of threshold voltage (Vth) as small as 0.04 were achieved by accurately controlling the fabrication process, which is so far the most stable distribution to our knowledge. On-state current (Ion), off-state current and on/off current ratio also exhibit high uniformity with low standard deviation of 0.50, 0.72 and 0.54, respectively. Given the high uniformity, high stability and high sensitivity, the CNT-TFTs are used as ultra-sensitive 5-hydroxymethyl cytosine (5-hmC) detecting devices for the first time, which is one of the important modified bases in DNA and plays an important role in epigenetics. After attachment of 5-hmC DNA, a reproducible and stable shift of 18.7–59% in Vth as well as a 31–54% change in Ion were observed in the transfer characteristics curves of CNT-TFTs. Thus, a detecting device of 5-hmC in DNA segments could be designed based on the highly uniform CNT-TFTs.
A novel nanomaterial composed of copper and carbon nanofibers (CuCNFs) decorated with Ag-doped TiO2 (Ag–TiO2) nanoparticles was prepared through electrospinning, carbonization and solvothermal treatment. The composites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and electrochemical impedance spectroscopy (EIS). The obtained composites were mixed with laccase and Nafion to construct novel hydroquinone biosensor. The electrochemical behavior of the novel biosensor was studied using cyclic voltammetry (CV) and chronoamperometry. The results demonstrated that the biosensor possessed a wide detection linear range (1.20–176.50μM), a good selectivity, repeatability, reproducibility and storage stability. This work provides a new material to design more efficient laccase (Lac) based biosensor for hydroquinone detection.
This study compared the susceptibility of different triangular silver nanoprisms (TSNPRs) towards the etching of hydrogen peroxide (H2O2), a catalytical product of glucose oxidase (GOx). The influence of capping agents and structural size have been explored towards the oxidation of silver nanoprisms. Results indicated that the etching of the TSNPRs was extremely effected by surface capping agents, in which citrate contributed a highest H2O2-sensitive effect in the absence of secondary capping ligands (e.g., glycerol and ethanol). Meanwhile, compared to bigger TSNPRs, smaller nanoprisms exhibited a different signal output of plasma resonance peak through intensity decrease rather than wavelength shift, making them more H2O2-etching susceptibile. In virtue of GOx etching-based system, TSNPRs with a small size and citrate capping were served as a substitute for big nanoprisms to sense glucose, offering a number of advantages such as high sensitivity, improved calibration, time-saving and extended detection ranges. Moreover, the small sized TSNPRs capping with citrate alone have been expected to be of great interest in the trace of GOx, providing an ultrahigh sensitive GOx etching-based analytical platform for point-of-care diagnostics towards other analytes (e.g., DNA, protein).
The biaxial and planar characteristics of surface stress produce a parabolic differential stress distribution inside the sensing zone of microcantilever biosensors, which can be used to design novel biosensors. The present work studies and compares the effect of parabolic and conventional rectangular-shaped piezoresistor placed inside this sensing zone on sensitivity of the biosensors. Two different cantilevers made of silicon and silicon dioxide with doped silicon as piezoresistor are used in five design variations. The cantilevers are characterized for their deflections, von Mises stresses, resonant frequencies and self-heating temperatures produced using ANSYS. Analytical models for predicting deflections in the cantilevers is presented and compared with numerical results obtained. Results show good compatibility between analytical and numerical values for deflection with a 4–5% average deviation and that parabolic designs have higher sensitivity.
Selectivity is significant to the practical applications of electrochemical biosensors in clinical and diagnostic field. In this paper, porous CeO2−x/C nanorods (NRs) derived from Ce-based metal organic framework (MOF) were synthesized and employed as substrate to construct uric acid biosensors with high sensitivity and selectivity at low working potential. The morphology, microstructures and elemental states of as-prepared samples were investigated by SEM, XRD, TEM and XPS systematically. It was found that a great amount of oxygen vacancies was introduced into the interstitial of CeO2 and nonstoichiometric CeO2/C (CeO2−x/C) nanorods based on Ce-MOF were formed under calcination in Ar atmosphere. The increased oxygen vacancies enabled the negatively shifting of the working potential towards H2O2 detection for CeO2−x/C nanorods, favoring the construction of biosensors based on the detection of H2O2. Uric biosensors based on CeO2−x/C NRs exhibited a high sensitivity of 220.0μA⋅cm−2⋅mM−1 and a linear range from 50μM to 1000μM at working potential of −0.4V versus SCE. It also exhibited superior selectivity toward interferents coexisting with uric acid in urine due to the low working potential.
Recent advances in miniaturized nano-based devices are rapidly extending the boundaries of biomedical technologies, particularly biosensors. Highly selective biosensors with the ability to simultaneously detect multiple targets were developed in recent years. The most eye-catching classifications of such biosensors coupled with the emergence of stimuli-responsive and CRISPR/Cas-sensitive systems. Furthermore, attractive features of wearable and implantable biosensors have led to the design of portable, remote controllable diagnostic systems for tackling healthcare challenges in every part of the world, especially in places with limited access to clinical resources. Nevertheless, there are still some barriers to widespread applications of biosensors due mainly to their high costs and the lack of a single biosensing device for highly selective targeting of multiple analytes. Herein, we review the latest developments in biomedical technologies with a focus on biosensors including smart stimuli-responsive, CRISPR/Cas-sensitive, wearable, and implantable biosensors to spark innovations in this field.
In the semiconductor industry, nanoscale devices have better ability to provide for biomolecules detection, but they face various problems during fabrication process, such as high doping concentration, random dopant fluctuation (RDF), higher production cost, low electrostatic control. To overcome these problems, charge plasma (CP) technique has been introduced by the formation of hafnium material at drain side and platinum material at source side with appropriate work-function. The proposed work charge plasma-based vertical-nanowire tunnel FET (CP-VNWTFET) has been designed and analyzed for biosensor application using different dielectric constant and gate underlap method by creating a cavity area under the gate metal. The sensitivity (S) of biosensor is calculated in terms of change in drain-current (Id) and transconductance (gm) by immobilizing the biomolecules such as Urease, Keratin, Streptavidin, ChOX, Zein, Gluten using gate underlap and dielectric modulation technique. The performance parameters like subthreshold slope (SS), off-current (Ioff), on-current (Ion), on/off current ratio (Ion∕Ioff) of the CP-VNWTFET have also been observed while varying the neutral and charged biomolecules at various biased conditions. The device is simulated by using Silvaco ATLAS simulator. The proposed device has been found to be suitable for low power sensor design application.
Radiotherapy is a simple and effective method for the treatment of rhinitis cancer, but some patients are resistant to radiotherapy and affect the curative effect. Previous studies have confirmed that miR-205 can be used as a biomarker for the feasibility of radiotherapy in nasopharyngeal carcinoma (NPC). In this study, a biosensor for the detection of miR-205 was constructed by using graphene oxide (GO) and fluorescent DNA probes, and using DNase I to generate fluorescent signals for cyclic amplification. The results showed that the lowest detection limit of this sensor for detecting miR-205 was 475 pM, which was 4.86 times lower or 4.86 times better than that of conventional methods without amplification, and showed better detection specificity. It is expected to provide a convenient and effective tool for studying the radio resistance mechanism of NPC and for personalized therapy for NPC patients.
Receptor-functionalized membranes provide a new paradigm for developing mechanical biosensors. However, the lower sensitivity of these biosensors is still a challenge. In this research, a sensitive and thin (1.5 μm) gold nanoparticles-polydimethylsiloxane (AuNPs-PDMS) membrane is fabricated by reducing HAuCl4. Experimental results reveal that surface stress deforms the AuNPs-PDMS membrane, further increasing the resistance due to the tunneling mechanism and conductive percolation. During the functional process, the resistance change is consistent with theoretical prediction. The relative resistance change demonstrates a linear relationship with the glucose concentration. The biosensors exhibit a wider linear range for glucose from 0 to 30mM with a lower detection limit of 0.035mM. AuNPs-PDMS thin membrane-based surface stress biosensor shows promising application prospects to detect biomolecules.
In this paper for the first time, we have studied various structures of nanosheet field-effect transistors (NSFET) and the effect of various devices and process parameters such as nanosheet width, length, interspacing, S/D doping, channel doping, random dopant fluctuations studied on these device structures. Comparative analysis has been done between JL-NSFET, GS-JL-NSFET, JL-SiGeNSFET and JL-GS-SiGeNSFET in terms of analog parameters. Nanosheet-based FETs are likely to be the successor of FinFET beyond the 5-nm node. NSFETs have better control over gate, variable sheet width and more current per device footprint which gives them the advantage of circuit design versatility. NSFET offers better gate control, better current and switching per device footprint. NSFETs are preferred over NWFETs due to better electrostatics, greater channel widths, decreased SCEs and increased device reliability.
There is a growing realization that cell-to-cell variations in gene expression have important biological consequences underlying phenotype diversity and cell fate. Although analytical tools for measuring gene expression, such as DNA microarrays, reverse-transcriptase PCR and in situ hybridization have been widely utilized to discover the role of genetic variations in governing cellular behavior, these methods are performed in cell lysates and/or on fixed cells, and therefore lack the ability to provide comprehensive spatial-dynamic information on gene expression. This has invoked the recent development of molecular imaging strategies capable of illuminating the distribution and dynamics of RNA molecules in living cells. In this review, we describe a class of molecular imaging probes known as molecular beacons (MBs), which have increasingly become the probe of choice for imaging RNA in living cells. In addition, we present the major challenges that can limit the ability of MBs to provide accurate measurements of RNA, and discuss efforts that have been made to overcome these challenges. It is envisioned that with continued refinement of the MB design, MBs will eventually become an indispensable tool for analyzing gene expression in biology and medicine.
This paper presents a novel biosensor for bitter substance detection on the basis of light addressable potentiometric sensor (LAPS). Taste receptor cells (TRCs) were used as sensitive elements, which can respond to different bitter stimuli with extreme high sensitivity and specificity. TRCs were isolated from the taste buds of rats and cultured on the surface of LAPS chip. Due to the unique advantages such as single-cell recording, light addressable capability, and noninvasiveness, LAPS chip was used as secondary transducer to monitor the responses of TRCs by recording extracelluar potential changes. The results indicate LAPS chip can effectively record the responses of TRCs to different bitter substances used in this study in a real-time manner for a long-term. In addition, by performing principal component analysis on the LAPS recording data, different bitter substances tested can be successfully discriminated. It is suggested this TRCs–LAPS hybrid biosensor could be a valuable tool for bitter substance detection. With further improvement and novel design, it has great potentials to be applied in both basic research and practical applications related to bitter taste detection.
The hollow core photonic crystal waveguide biosensor is designed and described. The biosensor was tested in experiments for artificial sweetener identification in drinks. The photonic crystal waveguide biosensor has a high sensitivity to the optical properties of liquids filling up the hollow core. The compactness, good integration ability to different optical systems and compatibility for use in industrial settings make such biosensor very promising for various biomedical applications.
Bacterial infection is an acute infection caused by pathogens or conditional pathogens, which leads to severe disease and even death. It has become a significant reason for diseases and deaths worldwide. Therefore, rapid and precise detection, diagnosis, and treatment in the early stage are the key to deal with bacterial infections. Over recent years, along with the advances in biomaterials and nanotechnology, numerous nanomaterial-based multifunctional probes have been extensively explored in the biomedical field. Because of their excellent optical properties, inorganic optical nanoprobes are used to rapidly detect bacterial infection in the early stage and show excellent antibacterial properties, which has a great application prospect in antibacterial therapy expected to reduce the risk of bacterial infection. In this mini-review, we generally overviewed and summarized recent progress on inorganic nanoparticle-based optical imaging techniques as a platform to construct functional theranostics for the efficient treatment of bacterial infections. The opportunities and challenges in the application of fluorescent optical nanoprobes are prospected.
Leukemia is one of the ten types of cancer that causes the biggest death in the world. Compared to other types of cancer, leukemia has a low life expectancy, so an early diagnosis of the cancer is necessary. A new strategy has been developed to identify various leukemia biomarkers by making blood cancer biosensors, especially by developing nanomaterial applications so that they can improve the performance of the biosensor. Although many biosensors have been developed, the detection of leukemia by using nanomaterials with electrochemical and optical methods is still less carried out compare to other types of cancer biosensors. Even the acoustic and calorimetric testing methods for the detection of leukemia by utilizing nanomaterials have not yet been carried out. Most of the reviewed works reported the use of gold nanoparticles and electrochemical characterization methods for leukemia detection with the object of study being conventional cancer cells. In order to be used clinically by the community, future research must be carried out with a lot of patient blood objects, develop non-invasive leukemia detection, and be able to detect all types of blood cancer specifically with one biosensor. This can lead to a fast and accurate diagnosis thus allowing for early treatment and easy periodic condition monitoring for various types of leukemia based on its biomarker and future design controlable via internet of things (IoT) so that why would be monitoring real times.
We demonstrated a biomimetic green synthesis of bimetallic Au–Ag nanoparticles (NPs) on graphene nanosheets (GNs). The spherical protein, ferritin (Fr), was bound onto GNs and served as the template for the synthesis of GN/Au–Ag nanohybrids. The created GN/Au–Ag nanohybrids were further utilized to fabricate a non-enzymatic amperometric biosensor for the sensitive detection of hydrogen peroxide (H2O2), and this biosensor displayed high performances to determine H2O2 with a detection limit of 20.0 × 10-6 M and a linear detection range from 2.0 μM to 7.0 mM.
Novel feather-like CeO2 microstructures were achieved by a thermal decomposition approach of Ce(OH)CO3 precursor. The Ce(OH)CO3 was obtained from a solvothermal method employing Ce(NO3)3.6H2O with C6H12N4 and C16H33(CH3)3NBr (CTAB) at 190∘C in a water–PEG-200 mixed solution. The feather-like CeO2 dendrite was obtained by thermal conversion of the feather-like Ce(OH)CO3 at 650∘C in air. A reasonable growth mechanism was proposed with the soft-template effect of PEG-200. The electrochemical behavior and enzyme activity of myoglobin (Mb) immobilized on CeO2–Nafion modified glassy carbon electrode (GCE) are demonstrated by cyclic voltammetric measurements. The results indicate that CeO2 can obviously promote the direct electron transfer between the Mb redox centers and the electrode. The Mb on CeO2–Nafion behaves as an elegant performance on the electrochemical reduction of trichloroacetic acid (TCA) from 0.32μM to 2.28μM. The detection limit is estimated to be 0.08μM.
Gold nanoparticles are the most extensively studied nanomaterials for biomedical application due to their unique properties, such as rapid and simple synthesis, large surface area, strong adsorption ability and facile conjugation to various biomolecules. The remarkable photophysical properties of gold nanoparticles have provided plenty of opportunities for the preparation of gold nanoparticles-based optical biosensors, while the excellent biocompatibility, conductivity, catalytic properties and large surface-to-volume ratio have facilitated the application of gold nanoparticles in the construction of electrochemical biosensors. In this review, we mainly detail the gold nanoparticles-based optical and electrochemical biosensors for biomedical application in the recent two years, which have exhibited greatly enhanced analytical performances in the detection of DNA, proteins and some important small molecules.
Tyrosyl-DNA Phosphodiesterase 1 (TDP1) was initially discovered by its ability to remove topoisomerase I (TOPI) covalently trapped to DNA. However, it has since been found to be involved in the repair of a number of DNA lesions other than TOPI–DNA complexes e.g., damages caused by ionizing radiation and free radical-based genotoxins. TDP1 has been reported to be posttranslational regulated, and in nonsmall cell lung cancer (NSCLC) it has been reported that the enzyme activity of TDP1 can be upregulated without detectable upregulation in protein amount. Activity and protein analyses are normally performed sequentially using radioactively labeled DNA substrates analyzed using gel-electrophoresis for the activity measurement and western blot or ELISA for protein measurement. We demonstrate here that our previously developed TDP1 nanosensor due to the optical real-time readout can be combined with ELISA measurement into one assay facilitating measurement of both the enzymatic activity and the protein amount of TDP1. We show that the combined assay can be used for measurements both in cell line-based studies and for measurement in clinical tissue samples. Due to all measurements being performed in the exact same aliquot of cell or tissue extract, the combined assay allows the use of minimal amount of cells or tissue and without additional incubation steps compared to the normal ELISA procedure. Measuring protein amount and activity within the same portion of extract also minimizes the risk of variation being introduced when comparing amount to activity. Since the assay only uses small amounts of extract, it requires no advanced equipment besides a plate reader, and can work in whole-cell or tissue extract. We expect that it could be useful for analysis of posttranslational modifications influencing enzymatic activities both in basic research and in clinical studies.
The aim of this paper is to outline and discuss novel and promising findings focusing on (i) the synthesis of fluorescent silver nanoclusters (NCs) using DNA as the stabilizing scaffolds, (ii) the origins of fluorescence and (iii) recent applications in biosensing and imaging. By reviewing the recent synthesis methods and applications of DNA-based silver NCs, we hope to demonstrate that these novel nanolights have the potential to be successful in biomedicine beyond their typically envisioned purposes.
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