Integrated Sandwich-Paper 3D Cell Sensing Device to In Situ Wirelessly Monitor H2O2 Released from Living Cells.

Point-of-care testing (POCT) has attracted great interest because of its prominent advantages of rapidness, precision, portability, and real-time monitoring, thus becoming a powerful biomedical device in early clinical diagnosis and convenient medical treatments. However, its complicated manufacturing process and high expense severely impede mass production and broad applications. Herein, an innovative but inexpensive integrated sandwich-paper three-dimensional (3D) cell sensing device is fabricated to in situ wirelessly detect H2O2 released from living cells. The paper-based electrochemical sensing device was constructed by a sealed sandwiched bottom plastic film/fiber paper/top hole-centered plastic film that was printed with patterned electrodes. A new (Fe, Mn)3(PO4)2/N-doped carbon nanorod was developed and immobilized on the sensing carbon electrode while cell culture solution filled the exposed fiber paper, allowing living cells to grow on the fiber paper surrounding the electrode. Due to the significantly shortening diffusion distance to access the sensing sites by such a unique device and a rationally tuned ratio of Fe2+/Mn2+, the device exhibits a fast response time (0.2 s), a low detection limit (0.4 µM), and a wide detection range (2-3200 µM). This work offers great promise for a low-cost and highly sensitive POCT device for practical clinic diagnosis and broad POCT biomedical applications.

Graphdiyne marries PEDOT:PSS to form high-stable heterostructure from 2-unstable components toward ultra-low detection limit of uric acid detection in sweat.

PEDOT: PSS has been used as a biomimetic uric acid (UA) sensor but suffers from unfortunate low detection limit (LOD), narrow detection range and poor stability. Herein, we get graphdiyne (GDY) marry PEDOT:PSS to create a very stable GDY@PEDOT:PSS heterostructure for a biomimetic UA sensor, which accomplishes the lowest LOD (6 nM), the widest detection range (0.03 µM-7 mM) and the longest stability (98.1% for 35 days) among the related UA sensors. The sensor was successfully used to in situ real-time detection of  UA in sweat. The enhancement mechanisms of the sensor were investigated, and results discover that C≡C of GDY and C = C of PEDOT:PSS can cross-link each other by π-π interactions, making not only the former strongly resistant against oxidation deterioration, but also causes the latter to efficiently prevent water swelling of polymer for poor conductivity, thereby leading to high stability from both components. While the stabilized heterostructure can also offer more active sites by enhanced absorption of UA via π-π interactions for highly sensitive detection of UA. This work holds great promise for a practical sweat UA sensor while providing scientific insight to design a stable and electrocatalytically active structure from two unstable components.

Single-Atom Iron Anchored on 2-D Graphene Carbon to Realize Bridge-Adsorption of O-O as Biomimetic Enzyme for Remarkably Sensitive Electrochemical Detection of H2O2.

Single-atom catalysis is mainly focused on its dispersed high-density catalytic sites, but delicate designs to realize a unique catalysis mechanism in terms of target reactions have been much less investigated. Herein an iron single atomic site catalyst anchored on 2-D N-doping graphene (Fe-SASC/G) was synthesized and further employed as a biomimetic sensor to electrochemically detect hydrogen peroxide, showing an extremely high sensitivity of 3214.28 µA mM-1 cm-2, which is much higher than that (6.5 µA mM-1 cm-2) of its dispersed on 1-D carbon nanowires (Fe-SASC/NW), ranking the best sensitivity among all reported Fe based catalyst at present. The sensor was also used to successfully in situ monitor H2O2 released from A549 living cells. The mechanism was further systematically investigated. Results interestingly indicate that the distance between adjacent single Fe atomic catalytic sites on 2-D graphene of Fe-SASC/G matches statistically well with the outer length of bioxygen of H2O2 to promote a bridge adsorption of -O-O- for simultaneous 2-electron transfer, while the single Fe atoms anchored on distant 1-D nanowires in Fe-SASC/NW only allow an end-adsorption of oxygen atoms for 1-electron transfer. These results demonstrate that Fe-SASC/G holds great promise as an advanced electrode material in selective and sensitive biomimetic sensor and other electrocatalytic applications, while offering scientific insights in deeper single atomic catalysis mechanisms, especially the effects of substrate dimensions on the mechanism.

Combining complement fixation and luminol chemiluminescence for ultrasensitive detection of avian influenza A rH7N9.

The complement fixation test (CFT) is a serological test that can be used to detect the presence of either a specific antibody or antigen to diagnose infections. In a conventional CFT, the assay result is determined by observing the clarity of the reaction solution or the sediment of red cells by the naked eye. Although the assay conditions are thereafter simplified, the sensitivity of the assay would be sacrificed due to the limitation of bulk observation. Inspired by the forensic scientists to examine blood at the scene of the crime, we rationally argued that the luminol chemiluminescence (CL) reaction could be applied in the CFT to sense physiological complement-mediated haemolytic phenomena for sensitive protein detection. The combination of the CFT and the luminol CL system was demonstrated in detection of rH7N9, a recombinant avian influenza virus protein. The testing can be accomplished within 2.5 h and the linear detection range covers 0.25 fg mL(-1) to 25 ng mL(-1). The feasibility of the CL based CFT in assaying a real biopsy was successfully demonstrated by specifically detecting rH7N9 and the carcinoembryonic antigen (CEA) in human serum. This new type of protein detection approach inherits the beauty of complement-mediated assay, such as being fast, and no protein immobilization, blocking and washing. In addition, the participation of luminol CL enables us to quantitatively analyse the intensity of a haemeolysis process, ameliorating the limitation of bulk observation in traditional CFT. It is anticipated that the luminol CL-CFT assay would be particularly suitable for investigation of small molecules, toxins, and short peptides.

Dual signal amplification of surface plasmon resonance imaging for sensitive immunoassay of tumor marker.

Surface plasmon resonance imaging (SPRi) is an intriguing technique for immunoassay with the inherent advantages of being high throughput, real time, and label free, but its sensitivity needs essential improvement for practical applications. Here, we report a dual signal amplification strategy using functional gold nanoparticles (AuNPs) followed by on-chip atom transfer radical polymerization (ATRP) for sensitive SPRi immunoassay of tumor biomarker in human serum. The AuNPs are grafted with an initiator of ATRP as well as a recognition antibody, where the antibody directs the specific binding of functional AuNPs onto the SPRi sensing surface to form immunocomplexes for first signal amplification and the initiator allows for on-chip ATRP of 2-hydroxyethyl methacrylate (HEMA) from the AuNPs to further enhance the SPRi signal. High sensitivity and broad dynamic range are achieved with this dual signal amplification strategy for detection of a model tumor marker, α-fetoprotein (AFP), in 10% human serum.

Electromagnetic Field Drives the Bioelectrocatalysis of γ-Fe2O3-Coated Shewanella putrefaciens CN32 to Boost Extracellular Electron Transfer.

The microbial hybrid system modified by magnetic nanomaterials can enhance the interfacial electron transfer and energy conversion under the stimulation of a magnetic field. However, the bioelectrocatalytic performance of a hybrid system still needs to be improved, and the mechanism of magnetic field-induced bioelectrocatalytic enhancements is still unclear. In this work, γ-Fe2O3 magnetic nanoparticles were coated on a Shewanella putrefaciens CN32 cell surface and followed by placing in an electromagnetic field. The results showed that the electromagnetic field can greatly boost the extracellular electron transfer, and the oxidation peak current of CN32@γ-Fe2O3 increased to 2.24 times under an electromagnetic field. The enhancement mechanism is mainly due to the fact that the surface modified microorganism provides an elevated contact area for the high microbial catalytic activity of the outer cell membrane's cytochrome, while the magnetic nanoparticles provide a networked interface between the cytoplasm and the outer membrane for boosting the fast multidimensional electron transport path in the magnetic field. This work sheds fresh scientific light on the rational design of magnetic-field-coupled electroactive microorganisms and the fundamentals of an optimal interfacial structure for a fast electron transfer process toward an efficient bioenergy conversion.

Tuning metal atom doped interface of electrospinning nanowires to toward fast bioelectrocatalysis.

Metal doping plays a key role in overcoming inefficient extracellular electron transfer between electrode interface and electricity-producing microorganisms. However, it is unknown whether different metals play distinctive roles in the doping process. Herein, three different metal ions (Fe, Ni and Cu) are added to the spinning precursor to obtain the corresponding electrospinning metal doped carbon nanofibers. It is found that the maximum output power of iron doped carbon nanofiber anode is 641.96 mW m-2, which is better than that of nickel doped carbon nanofiber (411.26 mW m-2) and copper doped carbon nanofiber (336.01 mW m-2), as well as 7.62 times higher than that of CNF. The results proved that due to the various number and types of active sites formed, as well as the distinction in surface morphology and structure, the electronegativity of each material is different. The different bio-abiotic interface could affect the direct contact between the anode interface and the extracellular protein of electricity producing microorganisms, which leading to a significant gap in the improvement of bioelectrocatalytic performance of different metal anode materials. This work provides a synthetic idea for designing highly efficient anode materials with directional metal modification and interface regulation.

Implementation of π-π interaction in AuNPs@GDY to boost the bioelectrocatalysis in enzymatic biofuel cells.

The main challenges (sluggish electron transfer, low energy density) hinder the future application of enzymatic biofuel cells (EBFCs), which urgent to take effective measures to solve these issues. In this work, a composite of Au nanoparticles decorated graphdiyne (AuNPs@GDY) is fabricated and employed as the carrier of enzyme (G6PDH), and a mechanism based on π-π interaction of electron transfer is proposed to understand bioelectrocatalysis processes. The results show that the AuNPs@GDY composite exhibits the highest current density among the three materials (GDY, AuNPs, and AuNPs@GDY), which is 3.4 times higher than that of GDY and 2.5 times higher than that of AuNPs. Furthermore, the results reveal that the AuNPs could increase the loading of enzymes and provide more active site for reaction, while GDY provides highly π-conjugated structure and unique sp/sp2-hybridized linkages interface. This work provides new insights to explore a theoretical basis for the development of more efficient bioelectrocatalytic systems.

Screen printed electrodes on interfacial Pt-CuO/carbon nanofiber functional ink for real-time qualification of cell released hydrogen peroxide.

Screen printed electrode (SPE) on carbon-based inks exhibits promising applications in biosensing, environment protection and food safety. We report here a unique carbon-based material comprising Pt-CuO nanocrystal interfacially anchored on functionalized carbon nanofiber (Pt-CuO@FCNF) and its functional ink to build SPE for ultrasensitive detection of cell released H2O2. Pt-CuO@FCNF is fabricated using a one-pot and mass production method through direct pyrolysis of Pt and CuO precursors together with FCNF. FCNF with 1-D structure and high electrical conductivity can interfically anchor Pt-CuO nanocrystal, which synergically promotes rich active site and catalytic activity towards H2O2. Pt-CuO@FCNF exhibits a wide linear response of 0.4 µM-11 mM, a low detection limit of 17 nM, a fast response time of 1.0 s, and good selectivity. Eventually, Pt-CuO@FCNF SPE realizes real-time and ultrasensitive qualification of H2O2 released from both normal and cancer cells.

Electrospinning Mo-Doped Carbon Nanofibers as an Anode to Simultaneously Boost Bioelectrocatalysis and Extracellular Electron Transfer in Microbial Fuel Cells.

The sluggish electron transfer at the interface of microorganisms and an electrode is a bottleneck of increasing the output power density of microbial fuel cells (MFCs). Mo-doped carbon nanofibers (Mo-CNFs) prepared with electrostatic spinning and high-temperature carbonization are used as an anode in MFCs here. Results clearly indicate that Mo2C nanoparticles uniformly anchored on carbon nanowire, and Mo-doped anodes could accelerate the electron transfer rate. The Mo-CNF ΙΙ anode delivered a maximal power density of 1287.38 mW m-2, which was twice that of the unmodified CNFs anode. This fantastic improvement mechanism is attributed to the fact that Mo doped on a unique nanofiber surface could enhance microbial colonization, electrocatalytic activity, and large reaction surface areas, which not only enable direct electron transfer, but also promote flavin-like mediated indirect electron transfer. This work provides new insights into the application of electrospinning technology in MFCs and the preparation of anode materials on a large scale.

Graphdiyne chelated AuNPs for ultrasensitive electrochemical detection of tyrosine.

Tyrosine (Tyr) is a kind of amino acid that can regulate emotions and stimulate the nervous system, and it is of great importance to realize its ultrasensitive detection. A unique material of graphdiyne chelated AuNPs (GDY@AuNPs) is designed and developed to realize high-performance electrochemical sensing of Tyr. GDY promotes the absorption of Tyr via π-π interaction, and its CC strongly chelates with AuNPs for greatly improved sensitivity. GDY@AuNPs delivers a sensitivity of up to 181.2 µA mM-1 cm-2 and a wide range of 0.1-600 µM, among the best for carbon or AuNPs-based materials for the detection of Tyr. It demonstrates the accurate detection of Tyr in human sweat for potential practical applications.

Interfacial Regulation of ZIF-67 on Bacteria to Generate Bifunctional Sensing Material on Chip for Qualifying Cell-Released Reactive Oxygen Species.

Cell's activities are highly dependent on signal molecules, of which reactive oxygen species of the superoxide anion (O2•-) and hydrogen peroxide (H2O2) are important ones that always work together to regulate biological processes such as apoptosis and oxidative stress. It is of significance to realize simultaneous qualification of O2•- and H2O2 but it still faces challenges particularly in live-cell assay with a complex environment. We report the design of a bifunctional sensing material by interfacially regulating ZIF-67 on bacteria Shewanella putrefaciens to generate cobalt nanoparticles/nitrogen-doped porous carbon nanorods (Co/N-doped CNRs) and its sensing chip for qualifying cell-released O2•- and H2O2. Co/N-doped CNRs exhibit unique properties including porous structure for significantly increased reaction surface area and coordinating Co nanoparticles for rich active sites. The bifunctional Co/N-doped CNRs is used to fabricate the electrochemical sensing chip, which achieves a fast response time (0.5 s for O2•-, 1.9 s for H2O2), a low detection limit (0.69 nM for O2•-, 2.25 µM for H2O2), and a remarkably high sensitivity (792.30 µA·µM-1·cm-2 for O2•-, 153.91 µA·mM-1·cm-2 for H2O2), among the best of reported bifunctional nanozymes.

Doping molybdenum oxides with different non-metal atoms to promote bioelectrocatalysis in microbial fuel cells.

The sluggish extracellular electron transfer has been known as one of the bottlenecks to limit the power density of microbial fuel cells (MFCs). Herein, molybdenum oxides (MoOx) are doped with various types of non-metal atoms (N, P, and S) by electrostatic adsorption, followed by high-temperature carbonization. The as-prepared material is further used as MFC anode. Results indicate that all different elements-doped anodes can accelerate the electron transfer rate, and the great enhancement mechanism is attributed to synergistic effect of dopped non-metal atoms and the unique MoOx nanostructure, which offers high proximity and a large reaction surface area to promote microbe colonization. This not only enables efficient direct electron transfer but also enriches the flavin-like mediators for fast extracellular electron transfer. This work renders new insights into doping non-metal atoms onto metal oxides toward the enhancement of electrode kinetics at the anode of MFC.

Synthesis of NiO/Nitrogen-Doped Carbon Nanowire Composite with Multi-Layered Network Structure and Its Enhanced Electrochemical Performance for Supercapacitor Application.

Multi-layered NiO nanowires linked with a nitrogen-doped carbon backbone grown directly on flexible carbon cloth (NiO/NCBN/CC) was successfully fabricated with a facile synthetic strategy. The NiO/NCBN/CC was further used as a binding-free electrode for flexible energy storage devices, showing a boosted performance including a high capacitance of 1039.4 F g-1 at 1 A g-1 and an 83.4% capacitance retention ratio. More importantly, after 1500 cycles, the capacitance retention can achieve 72.5% at a current density of 20 A g-1. The excellent electrochemical properties of the as-prepared NiO/NCBN/CC are not only attributed to the multi-layered structure that can help to tender unimpeded channels and accommodate the electrolyte ions around the electrode interface during the charge-discharge process, but is also due to the link between the NiO and N-doped carbon backbone and the nitrogen doping on the carbon substrate, which results in extra defects on the surface that could boost the interfacial electron transfer rate of the electrode.

Vanadium pentoxide flat-nanofiber networked thin layer-structure to initiate intercalated polymerization for rapidly producing superior conductive hydrogel and its biomimetic hydrogen peroxide sensing application.

Poly(3,4-ethylenedioxythiophene) (PEDOT)-based hydrogel has been studied extensively due to its low cost, good chemical/mechanical stability, printability and high biocompatibility, but still suffers from its relatively low conductivity and complex synthesis method. In this work, we use vanadium pentoxide (V2O5) flat-nanofiber networked thin layer-structure to boost EDOT-intercalation reaction for rapidly producing fiber-reinforced conductive gel (FCG), achieving superior conductivity of 10 S cm-1 and extremely fast production time (10 s). The superior FCG formation mechanism is ascribed to the V2O5 flat-nanofiber networked thin layer-structure allowing EDOT rapidly penetrating to inter-layers and replacing inside water molecules for polymerization to high-conductive FCG. The FCG can be used to print various patterns and are further used to fabricate a flexible biomimetic hydrogen peroxide (H2O2) sensor, delivering a high sensitivity of 2100 µA mM-1 cm-2, ranking the best among all flexible enzyme-free H2O2 sensors. More importantly, this flexible biomimetic H2O2 sensor is successfully applied to real-time detect living cells-secreted H2O2, demonstrating its application for in situ monitoring of small biomolecules released from living cells. This work offers a universal approach to synthesize high-conductive printable hydrogels by designing precursors meriting from both physics and chemistry, while holding great promise for mass-manufacturing inexpensive hydrogels in applications of sensing or wearable devices.

Highly stable branched cationic polymer-functionalized black phosphorus electrochemical sensor for fast and direct ultratrace detection of copper ion.

Copper ions (Cu2+) is an indispensable trace element in the process of metabolism and intake of excessive Cu2+ may lead to fatal diseases such as Alzheimer's disease. It is highly demanding to develop a sensitive, selective and convenient method for Cu2+ detection. In this work, thin-layer structured polyethyleneimine (PEI) decorated black phosphorus (BP) nanocomposite is one-step synthesized for an electrochemical sensor toward direct detection of Cu2+. This sensor achieves a wide detection range of 0.25-177 µM, a low detection limit of 0.02 µM much below the Environmental Protection Agency (EPA) maximum contaminant levels for drinking water (20 µM for Cu2+), and much faster response (1.5 s response time) and simpler operation than the conventional tedious anodic stripping voltammetry, ranking one of the best among all reported Cu2+ sensor. The great sensing enhancement is mainly due to a synergistic effect of BP and PEI of the composite, of which the former offers the reactivity while the latter splits the thick BP to thin-layer structured PEI-BP composite for larger reaction area. Meanwhile, a flexible sensor has been successfully fabricated and applied in detecting of Cu2+ in real samples of river, confirming the application feasibility of PEI-BP sensor in water environment control.

Screen-printed analytical strip constructed with bacteria-templated porous N-doped carbon nanorods/Au nanoparticles for sensitive electrochemical detection of dopamine molecules.

Dopamine (DA) as an important neurotransmitter plays an important role in physiological activities, and its abnormal level can cause diseases such as Parkinson's disease. However, the clinical analysis of DA mainly relies on time-consuming and expensive liquid chromatography and molecular spectrometer. We present here a design and fabrication of inexpensive strip sensor constructed from screen printed electrodes for sensitive and selective detection of DA. The ink used for printing the strips contains Shewanella putrefaciens-templated porous N-doped carbon nanorods (N-doped CN) and Au nanoparticles (Au NPs), in which the N-doping enhances CN's negative charge to electrostatically attract the positively charged DA with strong adsorption for achieving fast electron transfer. Moreover, results indicate that the Au NPs impregnation in N-doped CN renders much more catalytic reaction sites toward DA oxidation current. The strip sensor exhibits high sensitivity for DA detection with a broad linear range of 0.02-700 µM and a low detection limit of 0.007 µM as well as good selectivity and superior flexibility for great potential in wearable applications. The strip sensor further performs an accurate detection of DA in human serum, providing a powerful analytical tool for diagnosis of DA related diseases in clinical analysis.

Nitrogen doping to atomically match reaction sites in microbial fuel cells.

Direct electron transfer at microbial anodes offers high energy conversion efficiency but relies on low concentrations of redox centers on bacterium membranes resulting in low power density. Here a heat-treatment is used to delicately tune nitrogen-doping for atomic matching with Flavin (a diffusive mediator) reaction sites resulting in strong adsorption and conversion of diffusive mediators to anchored redox centers. This impregnates highly concentrated fixed redox centers in the microbes-loaded biofilm electrode. This atomic matching enables short electron transfer pathways resulting in fast, direct electrochemistry as shown in Shewanella putrefaciens (S. putrefaciens) based microbial fuel cells (MFCs), showing a maximum power output higher than the conventional non-matched nitrogen-doped anode based MFCs by 21 times. This work sheds a light on diffusion mediation for fast direct electrochemistry, while holding promise for efficient and high power MFCs.

A high-energy-state biomimetic enzyme of oxygen-deficient MnTiO3 nanodiscs for sensitive electrochemical sensing of the superoxide anion.

It is of great importance to determine the superoxide anion (O2˙-), a kind of active free radical that plays important roles in catalytic and biological processes. We present here a high-energy-state biomimetic enzyme with extraordinary activity for O2˙- by inducing surface oxygen defects in MnTiO3 nanodiscs. Oxygen defects enable surface rich active Mn sites with high oxidation ability, which significantly promote the adsorption and electro-oxidation of O2˙-. The oxygen deficient MnTiO3 towards O2˙- exhibits a sensitivity of 126.48 µA µM-1 cm-2 and a detection limit of 1.54 nM, among the best performance of O2˙- sensing platforms.

Flexible electronic skin with nanostructured interfaces via flipping over electroless deposited metal electrodes.

A novel and simple method was developed to quickly pattern and transfer electrodes with nanostructures for fabricating flexible electronic skin (E-skin). A nano/micro-structure embedded Cu electrode can be fabricated from a solution process-based electroless deposition (ELD) on a frosted plastic substrate and subsequently flipped over with an adhesive tape. The fine nano/microstructures on the Cu layer benefit the pressure-electric response of the pressure sensor, demonstrated a high sensitivity: 2.22 kPa-1. This fabricated flexible E-skin can be used for monitoring human physiological signals, such as wrist pulse and thumb bending. This fabrication method is an economical tool for fast prototyping cost-effective wearable electronics for the detection and prediction of diseases. It offers opportunity for researchers from resource-limited laboratories to work on miniaturized wearable devices.