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Gold (Au) nano-island arrays were deposited on the glass substrate to fabricate surface-enhanced Raman scattering (SERS) substrates by in-situ thermal evaporation (deposited and annealed samples at the same time). The optimal SERS intensity deposited by various thicknesses and in-situ annealing temperatures of Au nano-island arrays would be investigated. The biomolecules (adenine) were dropped on the well-designed SERS substrate for precise and quantitative SERS detection. The characterization of Au nano-island arrays SERS substrate would be evaluated by scanning electron microscope (SEM) and Raman spectroscopy. The results showed that the optimal deposition thickness and annealing temperature of Au nano-island arrays SERS substrate is about 14 nm and 200 °C respectively, which can construct the smallest interparticle spacing (W)/ particle diameter (D) ratio and the lowest reflection (%) and transmittance (%) to form the strongest SERS intensity. Moreover, finite-difference time-domain (FDTD) simulation of the electromagnetic field distributions on Au nano-island arrays displays the similar trend with the experimental results. The 14 nm deposition with 200 °C in-situ annealing temperature would display the highest density of hot-spots by FDTD simulation. The reproducible Au nano-island arrays SERS substrates with tunable surface roughness, W/D ratio, and lower reflection and transmittance show promising potential for SERS detection of biomolecules, bacteria, and viruses.
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Digital bio-detection has become one of the most appealing methods in recent years due to its excellent performance with ultra-sensitivity in detection of low-abundance targets. Traditional digital bio-detection needs the utilization of micro-chambers for physical isolation of targets, while the recently developed beads-based micro-chamber free one is attracting extensive attention, although there exist the disadvantages of overlaps between positive ("1") and negative ("0") signals as well as the decreased detection sensitivity in multiplexed mode. Here we propose a feasible and robust micro-chamber free digital bio-detection for multiplexed and ultrasensitive immunoassay based on encoded magnetic microbeads (EMMs) and tyramide signal amplification (TSA) strategy. An EMMs-based multiplexed platform is constructed by using a fluorescent encoding method, then a puissant signal amplification of positive events in TSA procedure is achieved via systematical revelation of key factors influences. For proof of concept, a three-plexed tumor markers detection is performed to evaluate our established platform. The detection sensitivity is comparable to the corresponding single-plexed assays and is also approximately 30-15,000 times improvement compared to the conventional suspension chip. Therefore, this multiplexed micro-chamber free digital bio-detection paves a promising way to be an ultrasensitive and powerful tool for clinical diagnosis.
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Biomarcadores de Tumor , Puntos Cuánticos , Microesferas , Inmunoensayo/métodos , Fenómenos MagnéticosRESUMEN
COVID-19 is one of the deadliest epidemics. This pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the role of dogs in spreading the disease in human society is poorly understood. This review sheds light on the limited susceptibility of dogs to COVID-19 infections which is likely attributed to the relatively low levels of angiotensin-converting enzyme 2 (ACE2) in the respiratory tract and the phylogenetic distance of ACE2 in dogs from the human ACE2 receptor. The low levels of ACE2 affect the binding affinity between spike and ACE2 proteins resulting in it being uncommon for dogs to spread the disease. To demonstrate the role of dogs in spreading COVID-19, we reviewed the epidemiological studies and prevalence of SARS-CoV-2 in dogs. Additionally, we discussed the use of detection dogs as a rapid and reliable method for effectively discriminating between SARS-CoV-2 infected and non-infected individuals using different types of samples (secretions, saliva, and sweat). We considered the available information on COVID-19 in the human-dog interfaces involving the possibility of transmission of COVID-19 to dogs by infected individuals and vice versa, the human-dog behavior changes, and the importance of preventive measures because the risk of transmission by domestic dogs remains a concern.
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Black phosphorus, as a novel two-dimensional nanomaterial, has received a lot of attention from researchers for its unique structure and properties. In recent years, with the increasing cross-sectional research related to black phosphorus 2D nanomaterials in various fields such as materials science, physics, chemistry, biology, and medicine, it has shown great potential for development and application in biomedicine. The excellent photoacoustic properties and good biocompatibility of black phosphorus 2D nanomaterials make them outstanding in tumor diagnosis and treatment. In this paper, the structure and properties, preparation, and functional modification of black phosphorus two-dimensional nanomaterials and their potential applications in the bio-detection and treatment of tumors, as well as the application progress of antibacterial were reviewed.
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With an ideal comfort level, sensitivity, reliability, and user-friendliness, wearable sensors are making great contributions to daily health care, nursing care, early disease discovery, and body monitoring. Some wearable sensors are imparted with hierarchical and uneven microstructures, such as microneedle structures, which not only facilitate the access to multiple bio-analysts in the human body but also improve the abilities to detect feeble body signals. In this paper, we present the promising applications and latest progress of functional microneedles in wearable sensors. We begin by discussing the roles of microneedles as sensing units, including how the signals are captured, converted, and transmitted. We also introduce the microneedle-like structures as power units, which depend on triboelectric or piezoelectric effects, etc. Finally, we summarize the cutting-edge applications of microneedle-based wearable sensors in biophysical signal monitoring and biochemical analyte detection, and provide critical thinking on their future perspectives.
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Thermo-responsive Raman-enhanced nanocapsules were successfully fabricated by Pluronic® F127 (F127) decorated with gold nanoparticles (AuNPs) for surface-enhanced Raman scattering (SERS) detection of biomolecules. F127 nanocapsules changes from hydrophilicity (swelling) to hydrophobicity (de-swelling) when the temperature increases from 15 °C to 37 °C, owing to the lower critical solution temperature (LCST) of F127 is about 26.5 °C. The size of nanocapsules would be enormous shrinking from 160 nm to 20 nm, resulting in a significant decrease in the distance between AuNPs to enhance hot spot effect, which increases the sensitivity of SERS detection. Based on the thermo-sensitive behavior, the ratio of AuNPs and F127 would be manipulated to find the optimal SERS enhancement effect. SERS nanocapsules can rapidly detect biomolecules (adenine and R6G) with limit of detection (LOD) lower than 10-6 M. In addition, the relatively difficult to detect clinical samples, carboxyl-terminal parathyroid hormone fragments (C-PTH), can also be measured by the thermo-responsive SERS nanocapsules developed in this work. It is expected the biomolecules can be adsorbed at low temperature (15 °C), as well as collected and concentrated at high temperature (37 °C) for SERS detection, to increase the sensitivity and stability of SERS detection.
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Nanopartículas del Metal , Nanocápsulas , Oro , Poloxámero , Polietilenos , Polipropilenos , Espectrometría Raman/métodosRESUMEN
The interdiction of restricted and hazardous biological agents presents challenges for any detection method due to the inherent complexity of sample type and accessibility. Detection capabilities for this category of agents are limited and restricted in their mobility, adaptability and efficiency. The potential for identifying biological agents through a volatile organic compound (VOC) signature presents an opportunity to use detection dogs in a real-time mobile capacity for surveillance and screening strategies. However, the safe handling and access to the materials needed for training detection dogs on restricted or hazardous biological agents prevents its broader application in this field. This study evaluated the use of a polymer-based training aid in a viral detection model using bovine viral diarrhea virus mimicking biosafety level 3+ agent conditions. After the biological agent-based odor was absorbed into the polymer, the aid was rendered safe for handling through a rigorous sterilization process. The viral culture-based training aid was then used to train a cohort of detection dogs (n = 6) to discriminate agent-based target odor in culture from relevant distractor odors including non-target biological agent-based odors. Following culture-based training, dogs were tested for generalization to aids with infected animal sample-based odors across five sample types (fecal, blood, nasal, saliva, and urine). Within the context of the polymer-based training aid system, dogs were successfully trained to detect and discriminate a representative biological viral agent-based odor from distractor odors with a 97.22% (±2.78) sensitivity and 97.11% (±1.94) specificity. Generalization from the agent-based odor to sample-based odors ranged from 65.40% (±8.98) to 91.90 % (±6.15) sensitivity and 88.61% (±1.46) to 96.00% (±0.89) specificity across the sample types. The restrictive nature for mimicking the access and handling of a BSL 3+ agent presented challenges that required a strict study design uncommon to standard detection dog training and odor presentation. This study demonstrates the need to further evaluate the utility and challenges of training detection dogs to alert to biological samples using safe and manageable training aids.
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Context: Molecular tests are useful in detecting COVID-19, but they are expensive in developing countries. COVID-19-sniffing dogs are an alternative due to their reported sensitivity (>80%) and specificity (>90%). However, most of the published evidence is experimental, and there is a need to determine the performance of the dogs in field conditions. Hence, we aimed to test the sensitivity and specificity of COVID-19-sniffing dogs in the field. Methods: We trained four dogs with sweat and three dogs with saliva of COVID-19-positive patients, respectively, for 4.5 months. The samples were obtained from a health center in Hermosillo, Sonora, with the restriction to spend 5 min per patient. We calculated sensitivity, specificity, and their 95% confidence intervals (CI). Results: Two sweat-sniffing dogs reached 76 and 80% sensitivity, with the 95% CI not overlapping the random value of 50%, and 75 and 88% specificity, with the 95% CI not overlapping the 50% value. The 95% CI of the sensitivity and specificity of the other two sweat dogs overlapped the 50% value. Two saliva-sniffing dogs had 70 and 78% sensitivity, and the 95% CI of their sensitivity and specificity did not overlap the 50% value. The 95% CI of the third dog's sensitivity and specificity overlapped the 50% value. Conclusion: Four of the six dogs were able to detect positive samples of patients with COVID-19, with sensitivity and specificity values significantly different from random in the field. We considered the performance of the dogs promising because it is reasonable to expect that with gauze exposed for a longer time to sweat and saliva of people with COVID-19, their detection capacity would improve. The target is to reach the sensitivity range requested by the World Health Organization for the performance of an antigen test (≥80% sensitivity, ≥97% specificity). If so, dogs could become important allies for the control of the COVID-19 pandemic, especially in developing countries.
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Achieving superhigh sensitivity is the ultimate goal for bio-detection in modern analytical science and life science. Among variable signal amplification strategies, nucleic acid amplification technologies are revolutionizing the field of bio-detection, providing greater possibilities in novel diagnosis achieving high efficiency, specificity, and cost-effectiveness. Nucleic acid amplification techniques (NAATs), such as Polymerase Chain Reaction (PCR), Rolling Circle Amplification (RCA), Loop-Mediated Isothermal Amplification (LAMP), Recombinase Polymerase Amplification (RPA), CRISPR-related amplification, and others are dominating methods employed in research and clinical settings. They each provide distinctively unique features that can offer desirable performance in terms of sensitivity, specificity, simplicity, stability, and cost. NAATs are in unmet demand in molecular diagnosis, especially in point-of-care scenario. This review will discuss the principles and recent advancements of each NAAT, respectively, revealing their strengths and challenges in achieving rapid and accurate bio-detection with a focus on point-of-care diagnosis. Furthermore, this review will explore the application of each of the technologies through the contemporary COVID-19 pandemic, analyzing their ability in point-of-care diagnosis of the COVID-19 with high sensitivity to emphasize significance of developing NAATs based methods in battling COVID-19. Finally, advantages and potentials of each NAAT in enhancements of sensitivity and specificity in bio-detection from bench side to the bedside will be discussed, aiming for full exploitation of capability of each NAAT. This review will provide novel aspects in the selection and combination of usages of various NAATs based on their distinctive characteristics and limitations. A possible advancing direction of future accurate POCT is also proposed.
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Técnicas Biosensibles , COVID-19 , COVID-19/diagnóstico , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Pandemias , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , SARS-CoV-2/genética , Sensibilidad y EspecificidadRESUMEN
Foodborne diseases have become a significant threat to public health worldwide. Development of analytical techniques that enable fast and accurate detection of foodborne pathogens is significant for food science and safety research. Assays based on lanthanide (Ln) ion-doped upconversion nanoparticles (UCNPs) show up as a cutting edge platform in biomedical fields because of the superior physicochemical features of UCNPs, including negligible autofluorescence, large signal-to-noise ratio, minimum photodamage to biological samples, high penetration depth, and attractive optical and chemical features. In recent decades, this novel and promising technology has been gradually introduced to food safety research. Herein, we have reviewed the recent progress of Ln3+-doped UCNPs in food safety research with emphasis on the following aspects: 1) the upconversion mechanism and detection principles; 2) the history of UCNPs development in analytical chemistry; 3) the in-depth state-of-the-art synthesis strategies, including synthesis protocols for UCNPs, luminescence, structure, morphology, and surface engineering; 4) applications of UCNPs in foodborne pathogens detection, including mycotoxins, heavy metal ions, pesticide residue, antibiotics, estrogen residue, and pathogenic bacteria; and 5) the challenging and future perspectives of using UCNPs in food safety research. Considering the diversity and complexity of the foodborne harmful substances, developing novel detections and quantification techniques and the rigorous investigations about the effect of the harmful substances on human health should be accelerated.
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Elementos de la Serie de los Lantanoides , Nanopartículas , Humanos , Luminiscencia , Análisis de Peligros y Puntos de Control Críticos , Elementos de la Serie de los Lantanoides/química , Nanopartículas/químicaRESUMEN
Rare Earth Upconversion nanoparticles (UCNPs) are a type of material that emits high-energy photons by absorbing two or more low-energy photons caused by the anti-stokes process. It can emit ultraviolet (UV) visible light or near-infrared (NIR) luminescence upon NIR light excitation. Due to its excellent physical and chemical properties, including exceptional optical stability, narrow emission band, enormous Anti-Stokes spectral shift, high light penetration in biological tissues, long luminescent lifetime, and a high signal-to-noise ratio, it shows a prodigious application potential for bio-imaging and photodynamic therapy. This paper will briefly introduce the physical mechanism of upconversion luminescence (UCL) and focus on their research progress and achievements in bio-imaging, bio-detection, and photodynamic therapy.
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In recent years, bimetallic nanocrystals have attracted great interest from many researchers. Bimetallic nanocrystals are expected to exhibit improved physical and chemical properties due to the synergistic effect between the two metals, not just a combination of two monometallic properties. More importantly, the properties of bimetallic nanocrystals are significantly affected by their morphology, structure, and atomic arrangement. Reasonable regulation of these parameters of nanocrystals can effectively control their properties and enhance their practicality in a given application. This review summarizes some recent research progress in the controlled synthesis of shape, composition and structure, as well as some important applications of bimetallic nanocrystals. We first give a brief introduction to the development of bimetals, followed by the architectural diversity of bimetallic nanocrystals. The most commonly used and typical synthesis methods are also summarized, and the possible morphologies under different conditions are also discussed. Finally, we discuss the composition-dependent and shape-dependent properties of bimetals in terms of highlighting applications such as catalysis, energy conversion, gas sensing and bio-detection applications.
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Nanoparticle synthesis using microorganisms and plants by green synthesis technology is biologically safe, cost-effective, and environment-friendly. Plants and microorganisms have established the power to devour and accumulate inorganic metal ions from their neighboring niche. The biological entities are known to synthesize nanoparticles both extra and intracellularly. The capability of a living system to utilize its intrinsic organic chemistry processes in remodeling inorganic metal ions into nanoparticles has opened up an undiscovered area of biochemical analysis. Nanotechnology in conjunction with biology gives rise to an advanced area of nanobiotechnology that involves living entities of both prokaryotic and eukaryotic origin, such as algae, cyanobacteria, actinomycetes, bacteria, viruses, yeasts, fungi, and plants. Every biological system varies in its capabilities to supply metallic nanoparticles. However, not all biological organisms can produce nanoparticles due to their enzymatic activities and intrinsic metabolic processes. Therefore, biological entities or their extracts are used for the green synthesis of metallic nanoparticles through bio-reduction of metallic particles leading to the synthesis of nanoparticles. These biosynthesized metallic nanoparticles have a range of unlimited pharmaceutical applications including delivery of drugs or genes, detection of pathogens or proteins, and tissue engineering. The effective delivery of drugs and tissue engineering through the use of nanotechnology exhibited vital contributions in translational research related to the pharmaceutical products and their applications. Collectively, this review covers the green synthesis of nanoparticles by using various biological systems as well as their applications.
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Surface-enhanced fluorescence (SEF) is rapidly becoming one of the main spectroscopic techniques for the detection of a variety of biomolecules and biomarkers. The main reasons for this trend are the high sensitivity and selectivity, robustness, and speed of this analytical method. Each year, the number of applications that utilize this phenomenon increases and with each such work, the complexity and novelty of the used substrates, procedures, and analytes rises. To obtain a clearer view of this phenomenon and research area, we decided to combine 76 valuable research articles from a variety of different research groups into this mini-review. We present and describe these works concisely and clearly, with a particular interest in the quantitative parameters of the experiment. These sources are classified according to the nature of the analyte, on the contrary to most reviews, which sort them by substrate nature. This point of view gives us insight into the development of this research area and the consequent increase in the complexity of the analyte nature. Moreover, this type of sorting can show possible future routes for the expansion of this research area. Along with the analytes, we can also pay attention to the substrates used for each situation and how the development of substrates affects the direction of research and subsequently, the choice of an analyte. About 108 sources and several interesting trends in the SEF research area over the past 25 years are discussed in this mini-review.
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In recent years, the rapid development of nanoscience and technology has provided a new opportunity for the development and preparation of new inorganic enzymes. Nanozyme is a new generation of artificial mimetic enzyme, which like natural enzymes, can efficiently catalyze the substrate of enzyme under mild conditions, exhibiting catalytic efficiency, and enzymatic reaction kinetics similar to natural enzymes. However, nanozymes exist better stability than native enzymes, it can still maintain 85 % catalytic activity in strong acid and alkali (pH 2~10) or large temperature range (4~90°C). This provides conditions for designing complex catalytic systems. In this review, we discussed the enzymatic attributes and biomedical applications of gold nanoclusters, including peroxidase-like, catalase-like, detection of heavy metal ions, and therapy of brain and cancer etc. This review can help us understand the current research status nanozymes.
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Bio-Detection Dogs (BDDs) are used in some high-income countries as a diagnostic intervention, yet little is known about their potential in low/middle-income countries with limited diagnostic resources. This exploratory study investigated the opportunities and implications of deploying BDDs as a mobile diagnostic intervention to identify people with asymptomatic malaria, particularly at ports of entry, as an important step to malaria elimination in a population. A qualitative study design consisting of participant observation, five focus group discussions and informal conversations was employed in The Gambia in April-May 2017. A disciplined German Shepherd companion dog (not trained as a BDD) was introduced to research participants and their perceptions recorded. Field-notes and discussions were transcribed, translated and analysed thematically. Most research participants viewed positively the possibility of using BDDs to detect malaria, with the major advantage of being non-invasive. Some concerns, however, were raised regarding safety and efficacy, as well as cultural issues around the place of dogs within human society. The Gambia is a rabies-endemic country, and unfamiliar dogs are not usually approached, with implications for how research participants perceived BDDs. Understanding such concerns and working with local people to address such issues must be part of any successful strategy to deploy BDDs in new settings. Bio-Detection Dogs represent a potentially non-invasive diagnostic tool for the detection of asymptomatic or chronic malaria infections, particularly in areas with very low parasite rates. However, it is important to understand local concerns and work closely with communities to address those concerns. Wider deployment of BDDs will also require careful planning and sustained financial support.
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Países en Desarrollo , Técnicas y Procedimientos Diagnósticos , Perros , Malaria/diagnóstico , Animales , Estudios de Factibilidad , Grupos Focales , Gambia , Humanos , Masculino , Aceptación de la Atención de Salud , Pobreza , Investigación CualitativaRESUMEN
Fluorescently encoded microbeads are in demand for multiplexed applications in different fields. Compared to organic dye-based commercially available Luminex's xMAP technology, upconversion nanoparticles (UCNPs) are better alternatives due to their large anti-Stokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate (PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swelling-based encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence, we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface. Methods to functionalize the surface of PEGDA microbeads (acrylic acid incorporation, polydopamine coating) reported thus far quench the fluorescence of UCNPs. Here, PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared. Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin (HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein (hCRP) and HSA protein by immobilizing anti-hCRP antibodies on green UCNPs.
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Bacteria-related pathogenic diseases are one of the major health problems throughout the world. Salmonella is a genus of rod-shaped Gram-negative enterobacteria of which more than 2600 serotypes have been identified. Infection with Salmonella can cause salmonellosis, a serious bacterial toxi-infection syndrome associated with gastroenteritis, and paralyphoid and typhoid fevers. Its rapid and sensitive detection is a key to the prevention of problems related to health. This paper describes the development of antibody and DNA sensors for Salmonella detection using a microfluidic-based electrochemical system. Commercial Salmonella typhimurium and Salmonella typhimurium from human stool samples were investigated using standard and nanomaterial-amplified antibody sensors. S. typhimurium could be detected down to 1 cfu mL-1. The specificity of immunoassay was tested by studying with non-specific bacteria including E. coli and S. aureus that revealed only 2.01% and 2.66% binding when compared to the target bacterium. On the other hand, the quantification of Salmonella DNA was investigated in a concentration range of 0.002â»200 µM using the developed DNA biosensor that demonstrated very high specificity and sensitivity with a detection limit of 0.94 nM. Our custom-designed microfluidic sensor offers rapid, highly sensitive, and specific diagnostic assay approaches for pathogen detection.
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Here, we demonstrate how sum frequency generation (SFG), a vibrational spectroscopy based on a nonlinear three-photon mixing process, may provide a direct and unique fingerprint of bio-recognition; This latter can be detected with an intrinsically discriminating unspecific adsorption, thanks to the high sensitivity of the second-order nonlinear optical (NLO) response to preferential molecular orientation and symmetry properties. As a proof of concept, we have detected the biological event at the solid/liquid interface of a model bio-active antigen platform, based on a solid-supported hybrid lipid bilayer (ss-HLB) of a 2,4-dinitrophenyl (DNP) lipid, towards a monoclonal mouse anti-DNP complementary antibody.
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Complejo Antígeno-Anticuerpo/química , Membrana Dobles de Lípidos/química , Sondas Moleculares/química , Animales , Membrana Dobles de Lípidos/síntesis química , Ratones , Análisis Espectral , Propiedades de Superficie , VibraciónRESUMEN
We present a new diagnostic technique of fundamental monomeric biomaterials that do not rely on any enzyme or chemical reaction. Instead, it only uses radio frequency (RF) signal analysis. The detection and classification of basic biomaterials, such as glucose and albumin, were demonstrated. The device was designed to generate a strong resonance response with glucose solution and fabricated by simple photolithography with PDMS (Polydimethylsiloxane) well. It even was used to detect the level of glucose in mixtures of glucose and albumin and in human serum, and it operated properly and identified the glucose concentration precisely. It has a detection limit about 100µM (1.8mg/dl), and a sensitivity about 58MHz per 1mM of glucose and exhibited a good linearity in human blood glucose level. In addition, the intrinsic electrical properties of biomaterials can be investigated by a de-embedding technique and an equivalent circuit analysis. The capacitance of glucose containing samples exhibited bell-shaped Gaussian dispersion spectra around 2.4GHz. The Albumin solution did not represent a clear dispersion spectra compared to glucose, and the magnitude of resistance and inductance of albumin was higher than that of other samples. Other parameters also represented distinguishable patterns to classify those biomaterials. It leads us to expect future usage of our technique as a pattern-recognizing biosensor.