One Step Quick Detection of Cancer Cell Surface Marker by Integrated NiFe-based Magnetic Biosensing Cell Cultural Chip

RGD peptides has been used to detect cell surface integrin and direct clinical effective therapeutic drug selection. Herein we report that a quick one step detection of cell surface marker that was realized by a specially designed NiF e-based magnetic biosensing cell chip combined with functionalized magnetic nanoparticles. Magnetic nanoparticles with 20-30 nm in diameter were prepared by coprecipitation and modified with RGD-4C, and the resultant RGD-functionalized magnetic nanoparticles were used for targeting cancer cells cultured on the NiF e-based magnetic biosensing chip and distinguish the amount of cell surface receptor-integrin.Cell lines such as Calu3, Hela, A549, CaF br, HEK293 and HUVEC exhibiting different integrin expression were chosen as test samples. Calu3, Hela, HEK293 and HUVEC cells were successfully identified. This approach has advantages in the qualitative screening test. Compared with traditional method, it is fast, sensitive, low cost,easy-operative, and needs very little human intervention. The novel method has great potential in applications such as fast clinical cell surface marker detection, and diagnosis of early cancer, and can be easily extended to other biomedical applications based on molecular recognition.

A short review on cell-based biosensing:challenges and breakthroughs in biomedical analysis

Current cell-based biosensors have progressed substantially from mere alternatives to molecular bioreceptors into enabling tools for interfacing molecular machineries and gene circuits with microelectronics and for developing groundbreaking sensing and theragnostic platforms.The recent literature concerning whole-cell biosensors is reviewed with an emphasis on mammalian cells,and the challenges and breakthroughs brought along in biomedical analyses through novel biosensing concepts and the synthetic biology toolbox.These recent innovations allow development of cell-based biosensing platforms having tailored performances and capable to reach the levels of sensitivity,dynamic range,and stability suitable for high analytic/medical relevance.They also pave the way for the construction of flexible biosensing platforms with utility across biological research and clinical applications.The work is intended to stimulate interest in generation of cell-based biosensors and improve their acceptance and exploitation.

Nanozymes in Point-of-Care Diagnosis:An Emerging Futuristic Approach for Biosensing

Nanomaterial-based artificial enzymes(or nanozymes) have attracted great attention in the past few years owing to their capability not only to mimic functionality but also to overcome the inherent drawbacks of the natural enzymes.Numerous advantages of nanozymes such as diverse enzyme-mimicking activities,low cost,high stability,robustness,unique surface chemistry,and ease of surface tunability and biocompatibility have allowed their integration in a wide range of biosensing applications. Several metal,metal oxide,metal–organic framework-based nanozymes have been exploited for the development of biosensing systems,which present the potential for point-of-care analysis. To highlight recent progress in the field,in this review,more than 260 research articles are discussed systematically with suitable recent examples,elucidating the role of nanozymes to reinforce,miniaturize,and improve the performance of point-of-care diagnostics addressing the ASSURED(a ordable,sensitive,specific,user-friendly,rapid and robust,equipment-free and deliverable to the end user) criteria formulated by World Health Organization. The review reveals that many biosensing strategies such as electrochemical,colorimetric,fluorescent,and immunological sensors required to achieve the ASSURED standards can be implemented by using enzyme-mimicking activities of nanomaterials as signal producing components. However,basic system functionality is still lacking. Since the enzyme-mimicking properties of the nanomaterials are dictated by their size,shape,composition,surface charge,surface chemistry as well as external parameters such as pH or temperature,these factors play a crucial role in the design and function of nanozyme-based point-of-care diagnostics. Therefore,it requires a deliberate exertion to integrate various parameters for truly ASSURED solutions to be realized. This review also discusses possible limitations and research gaps to provide readers a brief scenario of the emerging role of nanozymes in state-of-the-art POC diagnosis system development for futuristic biosensing applications.

Advances in Application of Biosensing Technology in Detection of Animal Epidemic Diseases

The development of rapid and sensitive detection technologies for animal epidemic diseases is very important to early diagnosis and disease control. Biosensing technology is a novel biological detection technology developed in recent years and has been listed as one of the five medical inspection technologies in the 21＂ century, which is considered as a rapid and effective technology for detection and diagnosis of animal epidemic diseases. In this paper, the latest research progresses on the application of biosensing technology in detection of bacterial infectious diseases, viral infectious diseases and parasitic diseases were summarized.

Recent progress in MOFs-based nanozymes for biosensing

Nanozymes are nanomaterials with enzyme-mimicking catalytic activity.Compared to natural enzymes,nanozymes show various properties such as easy to manufacture,stable,adjustable,and inexpensive.Nanozymes play key roles in biosensing,biocatalysis,and disease treatment.As an important kind of nanozymes,metal-organic framework(MOF)-based nanozymes are receiving a lot of attention due to their structural properties and composition.Rationally developing MOF with enzymes-like catalytic properties has opened new perspectives in biosensing.This review summarizes the up-to-date developments in synthesizing two-dimensional and three-dimensional MOF-based nanozymes and their applications in biosensing.Firstly,classification of nanozymes obtained by MOFs is categorized,and different properties of MOF-based nanozymes are described.Then,the distinctive applications of MOF-based nanozymes in identifying various analytes are thoroughly summarized.Finally,the recent challenges and progressive directions in this area are highlighted.

Hybridization chain reaction-based DNA nanomaterials for biosensing,bioimaging and therapeutics

DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient isothermal enzyme-free amplification strategy of DNA,generating nicked double helices with repeated units.Through the design of HCR hairpins,multiple nanomaterials with desired functions are assembled by DNA,exhibiting great potential in biomedical applications.Herein,the recent progress of HCR-based DNA nanomaterials for biosensing,bioimaging and therapeutics are summarized.Representative works are exemplified to demonstrate how HCR-based DNA nanomaterials are designed and constructed.The challenges and prospects of the development of HCR-based DNA nanomaterials are discussed.We envision that rationally designing HCR-based DNA nanomaterials will facilitate the development of biomedical applications.

High-gain signal-on PEDOT:PSS organic photoelectrochemical transistor biosensing modulated by a MXene/MOFs/NiO Schottky heterojunction

Herein we report a high-gain signal-on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(PEDOT:PSS)organic electrochemical transistor(OECT)biosensing using an accumulation-mode PEDOT:PSS OECT modulated by a light-fueled MXene/MOFs/Ni O Schottky heterojunction.In such a system,the MXene/MOFs/Ni O Schottky heterojunction exhibited superior gating effect,as it not only enabled the fast-directional charge transfer but also guaranteed the maximal accessibility of the electrolyte to topped 2D MXene with large surface area.In linkage with a bi-enzyme cascade system,the quinone derivatives produced by the cascade reaction of alkaline phosphatase(ALP)and tyrosinase(TYR)could serve as effective electron acceptors for the representative Ti_(3)C_(2)/PCN-224/Ni O heterojunction,underpinning an innovative method for sensitive detection of ALP activity with a low detection limit of 0.001 U L^(-1).Remarkably,the as-developed system demonstrated a remarkable current gain as high as near 10^(4),which to our knowledge is the highest one among existing OECT biosensory devices.This work represents a generic protocol to develop the novel signal-on PEDOT:PSS OECT platform towards biochemical detection and beyond.

Recent Advances in Triplet-Triplet Annihilation Upconversion for Bioimaging and Biosensing

Photon upconversion is an anti-Stokes process that converts low-energy photons into high-energy photons.The use of upconversion luminescence can avoid the autofluorescence of biological tissue and realize background-free bioimaging with a high signal-to-noise ratio at a low power density.In addition,the excitation of red or near-infrared light facilitates the reduction of photodamage in biological tissues and subsequent bioimaging of deep tissue features in vivo.Meanwhile,upconversion emission-mediated bio sensing offers both high sensitivity and low detection limits for quantitative analysis of the target substances in complicated biological samples.Due to its high upconversion quantum yield,low excitation power density,and tunable absorption and emission wavelengths,triplet-triplet annihilation upconversion(TTA-UC)has garnered considerable interest for bioimaging and biosensing.This review will introduce the fundamental concepts of TTA-UC,the factors that influence TTA-UC materials,and the methodologies for preparing TTA-UC materials.The important progress of TTA-UC in bioimaging and bio sensing in recent years will also be discussed in detail in vitro and in vivo.Furthermore,the current challenges of TTA-UC in bioimaging and biosensing will be discussed,along with potential solutions.

Deep-Red to Near-Infrared Carbon Dots in Biosensing and Bio-medical Applications

Comprehensive Summary,With the rapid development in the field of biomedical diagnosis and treatment,carbon dots(CDs)with favorable photostability,biocompatibility and high quantum yields for deep-red to near-infrared emission have attracted the attention of a majority of researchers.By enlarging the sp2 domain in the core of CDs,doping them with heteroatoms like nitrogen and sulfur,applying hydrothermal,electrochemical,or microwave-assisted techniques,CDs can be made with the aforementioned photoemission capabilities.In view of these excellent properties,CDs are flourishing in biosensing and biomedical applications,so that a thorough description and discussion of this topic is beneficial to capture the up-to-date progress of CDs in this field,providing suggestions and considerations for readers.

External stimulation-controlled dynamic DNA devices for biosensing and biomedical applications

DNA devices that can recognize molecular inputs and transform them into functional outputs in an autonomous manner have been actively pursued as versatile toolkits for controlled nanofabrication,molecular network regulation,biosensing and cellular function modulation.The introduction of external stimuli-responsive units not only ensures the programmability and functionality of DNA devices themselves,but also confers rapid,remote and reversible dynamic regulation capabilities.This facilitates on-demand activation and expands the application scope of dynamic DNA devices.Herein,an overview of recent advances in the construction of stimuli-responsive DNA devices that respond to different exogenous triggers,including physical stimuli(e.g.,light,thermal,magnetic field,and electric field),chemical stimuli(e.g.,supermolecules,pH,redox,and metal ions),and biological cues(e.g.,protein,biomolecule,and nucleic acid),and their controllable nanofabrication and biomedical application have been provided.The current challenges and potential solutions of these externally responsive DNA devices for their future advancements in this emerging field are also discussed.

Emerging advances in plasmonic nanoassemblies for biosensing and cell imaging

Integrating discrete plasmonic nanoparticles into assemblies can induce plasmonic coupling that produces collective plasmonic properties,which are not available for single nanoparticles.Theoretical analysis revealed that plasmonic coupling derived from assemblies could produce stronger electromagnetic field enhancement effects.Thus,plasmonic assemblies enable better performance in plasmon-based applications,such as enhanced fluorescence and Raman effects.This makes them hold great potential for trace analyte detection and nanomedicine.Herein,we focus on the recent advances in various plasmonic nanoassembles such as dimers,tetramers,and core-satellite structures,and discuss their applications in biosensing and cell imaging.The fabrication strategies for self-assembled plasmonic nanostructures are described,including top-down strategies,self-assembly methods linked by DNA,ligand,polymer,amino acid,or proteins,and chemical overgrowth methods.Thereafter,their applications in biosensor and cell imaging based on dark-field imaging,surface-enhanced Raman scattering,plasmonic circular dichroism,and fluorescence imaging are discussed.Finally,the remaining challenges and prospects are elucidated.

Real-time and label-free biosensing using moiré pattern generated by bioresponsive hydrogel

Bioresponsive hydrogels are smart materials that respond to various external stimuli and exhibit great potential as biosensors owing to their capability of real-time and label-free detection.Here,we propose a sensing platform based on bioresponsive hydrogels,employing the concept of moiré patterns.Two sets of line patterns with different pitch sizes are prepared;a hydrogel grating whose pitch size changes according to external stimuli and a reference grating with constant pitch size.The volume changes of the hydrogel caused by external stimuli changes the pitch size of the hydrogel grating,and subsequently,the pitch sizes of the moiré patterns(moiré signal),whose values can be obtained in a real-time and label-free manner through customized moiré microscopy and signal processing.After confirming that the pH-induced swelling of hydrogel could be monitored using moiré patterns,we performed moiré pattern-based detection of specific proteins using protein-responsive hydrogel that underwent shrinking via interaction with target proteins.Brain-derived neurotrophic factor and platelet-derived growth factor were selected as the model proteins,and our proposed system successfully detected both proteins at nanomolar levels.In both cases,the pitch size change of hydrogel grating was monitored much more sensitively using moiré patterns than through direct measurements.The changes in the moiré signals caused by target proteins were detected in ex-vivo environments using a custom-made intraocular lens incorporating the hydrogel grating,demonstrating the capability of the proposed system to detect various markers in intraocular aqueous humor,when implanted in the eye.

Advances in micro-nano biosensing platforms for intracellular electrophysiology

The establishment of a dependable electrophysiological detection platform is paramount for cardiology and neuroscience research.In the past decade,devices based on micro and nanoscale sensing and control technologies have been developed to construct electrophysiological platforms.Their unique morphological advantages and novel processing methods offer the potential for high-throughput,high-fidelity electrical signal recording.In this review,we analyze the structure,transmembrane strategies,and electrophysiological detection methods of active/passive micro and nano sensing platforms.We also provide an outlook on their vast potential for development in light of the opportunities and challenges facing micro and nano sensing technology,with the aim of pushing for higher-level electrophysiological platform construction to meet the needs of experimental research and clinical applications.

Recent progress in engineering near-infrared persistent luminescence nanoprobes for time-resolved biosensing/bioimaging

Persistent luminescence nanoprobes (PLNPs) can remain luminescent after ceasing excitation.Due to the ultra-long decay time of persistent luminescence (PersL),autofluorescence interference can be efficiently eliminated by collecting PersL signal after autofluorescence decays completely,thus the imaging contrast and sensing sensitivity can be significantly improved.Since near-infrared (NIR) light shows reduced scattering and absorption coefficient in penetrating biological organs or tissues,near-infrared persistent luminescence nanoprobes (NIR PLNPs) possess deep tissue penetration and offer a bright prospect in the areas of in vivo biosensing/bioimaging.In this review,we firstly summarize the design of different types of NIR PLNPs for biosensing/bioimaging,such as transition metal ions-doped NIR PLNPs,lanthanide ions-doped NIR PLNPs,organic molecules-based NIR PLNPs,and semiconducting polymer self-assembled NIR PLNPs.Notably,organic molecules-based NIR PLNPs and semiconductor self-assembled NIR PLNPs,for the first time,were introduced to the review of PLNPs.Secondly,the effects of different types of charge carriers on NIR PersL and luminescence decay of NIR PLNPs are significantly emphasized so as to build up an in-depth understanding of their luminescence mechanism.It includes the regulation of valence band and conduction band of different host materials,alteration of defect types,depth and concentration changes caused by ion doping,effective radiation transitions and energy transfer generated by different luminescence centers.Given the design and potential of NIR PLNPs as long-lived luminescent materials,the current challenges and future perspective in this rapidly growing field are also discussed.

Recent advances in autofluorescence-free biosensing and bioimaging based on persistent luminescence nanoparticles

Persistent luminescence nanoparticles (PLNPs) are a series of emerging luminescent nanomaterials which can emit persistently after ceasing the external excitation. Due to the long decay time of persistent luminescence, the background autofluorescence in complex sample and tissues can be effectively eliminated, thus significantly improving the sensitivity of bioanalysis. Besides, such a long decay time of luminescence also makes PLNPs valuable for long-term bioimaging. Benefiting from these merits, PLNPs have been widely used for biomedical applications, especially biosensing and bioimaging. In this review,we conclude the progress in the application of PLNPs at biosensing and bioimaging in recent years, and also provide our understanding of the prospects.

Superior LSPR substrates based on electromagnetic decoupling for on-a-chip high-throughput label-free biosensing

Localized surface plasmon resonance(LSPR)biosensing based on supported metal nanoparticles offers unparalleled possibilities for high-end miniaturization,multiplexing and high-throughput label-free molecular interaction analysis in real time when integrated within an opto-fluidic environment.However,such LSPR-sensing devices typically contain extremely large regions of dielectric materials that are open to molecular adsorption,which must be carefully blocked to avoid compromising the device readings.To address this issue,we made the support essentially invisible to the LSPR by carefully removing the dielectric material overlapping with the localized plasmonic fields through optimized wet-etching.The resulting LSPR substrate,which consists of gold nanodisks centered on narrow SiO2 pillars,exhibits markedly reduced vulnerability to nonspecific substrate adsorption,thus allowing,in an ideal case,the implementation of thicker and more efficient passivation layers.We demonstrate that this approach is effective and fully compatible with state-of-the-art multiplexed real-time biosensing technology and thus represents the ideal substrate design for high-throughput label-free biosensing systems with minimal sample consumption.

Surface molecular imprinting on g-C3N4 photooxidative nanozyme for improved colorimetric biosensing

Graphitic carbon nitride(g-C3 N4),as a visible-light-active organic semiconductor,has attracted growing attentions in photocatalysis and photoluminescence-based biosensing.Here,we demonstrated the intrinsic photooxidase activity of g-C3 N4 and then surface molecular imprinting on g-C3 N4 nanozymes was achieved for improved biosensing.Upon blue LED irradiation,the g-C3 N4 exhibited superior enzymatic activity for oxidation of chromogenic substrate like 3,3’,5,5’-tetramethylbenzidine(TMB)without destructive H2 O2.The oxidation was mainly ascribed to ·O2^-that was generated during light irradiation.The surface molecular imprinting on g-C3 N4 can lead to an over 1000-fold alleviation in matrix-interference from serum samples,4-fold improved enzymatic activity as well as enhanced substrate specificity comparing with bare g-C3 N4 during colorimetric sensing.Also,the MIP-g-C3 N4 possesses a high affinity to TMB with a Km value of only 22 μmol/L,much lower than other comment nanozymes like AuNPs,Fe3 O4 NPs,etc.It was successfully applied for detection of cysteine in serum sample with satisfactory recoveries.

Detection and monitoring prostate specific antigen using nanotechnology approaches to biosensing

Prostate cancer has a high incidence in men and remains the second cause of mortality due to cancer worldwide.As the development of the disease is greatly correlated to age,the identification of novel detection methods reliable,efficient,and cost effective is a matter of significant importance in the ageing population of western societies.The detection of the prostate specific antigen(PSA)in blood samples has been the preferred method for the detection and monitoring of prostate cancer over the past decades.Despite the indications against its use in massive population screening,PSA still remains the best studied biomarker for prostate cancer and the detection of its different forms and incorporation in multiplexed designs with other biomarkers still remains a highly valuable indicator in the theranostics of prostate cancer.The latest developments in the use of nanomaterials towards the construction of PSA biosensors are reviewed hereby.The incorporation of gold nanoparticles,silica nanoparticles and graphene nanostructures to biosensing devices has represented a big leap forward in terms of sensitivity,stability and miniaturization.Both electrochemical and optical detection methods for the detection of PSA will be reviewed herein.

Field-deployable rapid multiple biosensing system for detection of chemical and biological warfare agents

The threat of biological and chemical terror acts remains a growing worldwide concern.There is therefore a need to develop appropriate technology for the detection of chemical and biological warfare agents,with early identification intended for use by first responders.Here,we disclose the developed autonomous air sampling and detection system for evaluation of the presence of chemical and biological warfare agents that can be harmful to the population.The current device utilizes the designed mist generator-assisted air collection system(338 l min^(−1))and biosensing chip technologies,such as electrochemical measurement,Au nanoparticle-based localized surface plasmon resonance,and rapid microfluidic chip PCR for detection of minute concentrations lower than the mean lethal dose(LD_(50))of nerve gases(sarin and VX),toxic proteins(BTX/A/Hc and ricin),and pathogens(anthrax simulant).An operation time of only 5–15 min is needed for the collection and detection;sample preparation is already integrated into the system without the need for direct human intervention.In addition to the system’s sensitivity and ease of use,its portability makes it highly beneficial for first responders,which could aid in immediate risk assessment and mitigation of on-site events.

Synergistic in-situ growth of silver nanoparticles with nanozyme activity for dual-mode biosensing and cancer theranostics

A multifunctional nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles(AgNPs)on the complex of tannic acid(TA)and graphene quantum dots(GQDs)for the construction of dual-mode biosensing platform and cancer theranostics.The nanocomposite exhibits a hydrogen peroxide(H_(2)O_(2))-responsive degradation,in which Ag^(0)is oxidized to Ag^(+)along with the release of oxidized TA and GQDs.The degradation induces the decreased absorbance and enhanced fluorescence(FL)intensity due to the suppression of Forster resonance ene rgy transfer(FRET)in AgNPs@GQDs,which is employed for colorimetric/fluorescence dual-mode sensing of H_(2)O_(2).The intrinsic peroxidase-like activity of GQDs nanozyme can effectively catalyze the oxidation reaction,enhancing the detection sensitivity significantly.Based on the generation of H_(2)O_(2)from the oxidation of glucose with the catalysis of glucose oxidase(GOx),this nanoprobe is versatilely used for the determination of glucose in human serum.Further,through combining the H_(2)O_(2)-responsive degradation of AgNPs@GQDs with high H_(2)O_(2)level in cancer cells,the nanocomposites exhibit good performance in cancer cell recognition and therapy,in which the synergistic anticancer effect of Ag^(+)and oxidized TA contribute to effective cell death,and the liberated GQDs are used to monitor the therapeutic effect by cell imaging.