Label‐Free Attomolar Detection of Proteins Using Integrated Nanoelectronic and Electrokinetic Devices

High‐sensitivity screening of biomarkers is critical to areas ranging from early disease detection and diagnosis to bioterrorism surveillance. Here the development of integrated nanoelectronic and electrokinetic devices for label‐free attomolar detection of proteins is reported. Electrically addressable silicon nanowire field‐effect transistors and electrodes for electrokinetic transport are integrated onto a common sensor chip platform, and the nanowire devices are subsequently functionalized with receptors for selective biomarker detection. Nanowire devices modified with monoclonal antibody for prostate specific antigen exhibit close to a 10⁴ increase in sensitivity due to streaming dielectrophoresis and corresponding electrostatic contribution to the binding affinity after application of an AC electric field. The devices are also modified with receptors for cholera toxin subunit B and achieve a similar enhancement. These results show general applicability of this method, and could open up opportunities in early stage disease detection and the analysis of proteins from single cells.     

Electrical Graphene Aptasensor for Ultra‐Sensitive Detection of Anthrax Toxin with Amplified Signal Transduction

Detection of the anthrax toxin, the protective antigen (PA), at the attomolar (aM) level is demonstrated by an electrical aptamer sensor based on a chemically derived graphene field‐effect transistor (FET) platform. Higher affinity of the aptamer probes to PA in the aptamer‐immobilized FET enables significant improvements in the limit of detection (LOD), dynamic range, and sensitivity compared to the antibody‐immobilized FET. Transduction signal enhancement in the aptamer FET due to an increase in captured PA molecules results in a larger 30 mV/decade shift in the charge neutrality point (V_g,min) as a sensitivity parameter, with the dynamic range of the PA concentration between 12 aM (LOD) and 120 fM. An additional signal enhancement is obtained by the secondary aptamer‐conjugated gold nanoparticles (AuNPs‐aptamer), which have a sandwich structure of aptamer/PA/aptamer‐AuNPs, induce an increase in charge‐doping in the graphene channel, resulting in a reduction of the LOD to 1.2 aM with a three‐fold increase in the V_g,min shift.     

Reduced Graphene Oxide‐Functionalized High Electron Mobility Transistors for Novel Recognition Pattern Label‐Free DNA Sensors

We designed and constructed reduced graphene oxide (rGO) functionalized high electron mobility transistor (HEMT) for rapid and ultra‐sensitive detection of label‐free DNA in real time. The micrometer sized rGO sheets with structural defects helped absorb DNA molecules providing a facile and robust approach to functionalization. DNA was immobilized onto the surface of HEMT gate through rGO functionalization, and changed the conductivity of HEMT. The real time monitor and detection of DNA hybridization by rGO functionalized HEMT presented interesting current responses: a “two steps” signal enhancement in the presence of target DNA; and a “one step” signaling with random DNA. These two different recognition patterns made the HEMT capable of specifically detecting target DNA sequence. The working principle of the rGO functionalized HEMT can be demonstrated as the variation of the ambience charge distribution. Furthermore, the as constructed DNA sensors showed excellent sensitivity of detect limit at 0.07 fM with linear detect range from 0.1 fM to 0.1 pM. The results indicated that the HEMT functionalized with rGO paves a new avenue to design novel electronic devices for high sensitive and specific genetic material assays in biomedical applications.     

Highly Efficient (>10%) Flexible Organic Solar Cells on PEDOT‐Free and ITO‐Free Transparent Electrodes

A novel approach to fabricate flexible organic solar cells is proposed without indium tin oxide (ITO) and poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) using junction‐free metal nanonetworks (NNs) as transparent electrodes. The metal NNs are monolithically etched using nanoscale shadow masks, and they exhibit excellent optoelectronic performance. Furthermore, the optoelectrical properties of the NNs can be controlled by both the initial metal layer thickness and NN density. Hence, with an extremely thin silver layer, the appropriate density control of the networks can lead to high transmittance and low sheet resistance. Such NNs can be utilized for thin‐film devices without planarization by conductive materials such as PEDOT:PSS. A highly efficient flexible organic solar cell with a power conversion efficiency (PCE) of 10.6% and high device yield (93.8%) is fabricated on PEDOT‐free and ITO‐free transparent electrodes. Furthermore, the flexible solar cell retains 94.3% of the initial PCE even after 3000 bending stress tests (strain: 3.13%).     

DNA Sensors and Aptasensors Based on the Hemin/G‐quadruplex‐Controlled Aggregation of Au NPs in the Presence of L‐Cysteine

L‐cysteine induces the aggregation of Au nanoparticles (NPs), resulting in a color transition from red to blue due to interparticle plasmonic coupling in the aggregated structure. The hemin/G‐quadruplex horseradish peroxidase‐mimicking DNAzyme catalyzes the aerobic oxidation of L‐cysteine to cystine, a process that inhibits the aggregation of the NPs. The degree of inhibition of the aggregation process is controlled by the concentration of the DNAzyme in the system. These functions are implemented to develop sensing platforms for the detection of a target DNA, for the analysis of aptamer‐substrate complexes, and for the analysis of L‐cysteine in human urine samples. A hairpin DNA structure that includes a recognition site for the DNA analyte and a caged G‐quadruplex sequence, is opened in the presence of the target DNA. The resulting self‐assembled hemin/G‐quadruplex acts as catalyst that controls the aggregation of the Au NPs. Also, the thrombin‐binding aptamer folds into a G‐quadruplex nanostructure upon binding to thrombin. The association of hemin to the resulting G‐quadruplex aptamer‐thrombin complex leads to a catalytic label that controls the L‐cysteine‐mediated aggregation of the Au NPs. The hemin/G‐qaudruplex‐controlled aggregation of Au NPs process is further implemented for visual and spectroscopic detection of L‐cysteine concentration in urine samples.     

All‐Solution‐Processed Metal‐Oxide‐Free Flexible Organic Solar Cells with Over 10% Efficiency

All‐solution‐processing at low temperatures is important and desirable for making printed photovoltaic devices and also offers the possibility of a safe and cost‐effective fabrication environment for the devices. Herein, an all‐solution‐processed flexible organic solar cell (OSC) using poly(3,4‐ethylenedioxythiophene):poly‐(styrenesulfonate) electrodes is reported. The all‐solution‐processed flexible devices yield the highest power conversion efficiency of 10.12% with high fill factor of over 70%, which is the highest value for metal‐oxide‐free flexible OSCs reported so far. The enhanced performance is attributed to the newly developed gentle acid treatment at room temperature that enables a high‐performance PEDOT:PSS/plastic underlying substrate with a matched work function (≈4.91 eV), and the interface engineering that endows the devices with better interface contacts and improved hole mobility. Furthermore, the flexible devices exhibit an excellent mechanical flexibility, as indicated by a high retention (≈94%) of the initial efficiency after 1000 bending cycles. This work provides a simple route to fabricate high‐performance all‐solution‐processed flexible OSCs, which is important for the development of printing, blading, and roll‐to‐roll technologies.     

A Nanoelectronic Enzyme‐Linked Immunosorbent Assay for Detection of Proteins in Physiological Solutions

Semiconducting nanowires are promising ultrasensitive, label‐free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field‐effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening. A general solution to this limitation with the development of a hybrid nanoelectronic enzyme‐linked immunosorbent assay (ne‐ELISA) that combines the power of enzymatic conversion of a bound substrate with electronic detection is demonstrated. This novel configuration produces a local enzyme‐mediated pH change proportional to the bound ligand concentration. It is shown that nanowire FETs configured as pH sensors can be used for the quantitative detection of interleukin‐2 in physiologically buffered solution at concentrations as low as 1.6 pg mL^?1. By successfully bypassing the Debye screening inherent in physiological fluids, the ne‐ELISA promises wide applicability for ligand detection in a range of relevant solutions.     

Apta-biosensors for nonlabeled real time detection of human IgE based on carbon nanotube field effect transistors

In this study, we demonstrated the aptamer-based biosensor (apta-biosensor) using CNT-FET devices for label free detection of allergy diagnosis by IgE detection. In order to detect the IgE, two kinds of receptor (monoclonal IgE antibody and anti-IgE aptamer)-modified CNT-FET devices were fabricated. The binding event of the target IgE onto receptors was detected by monitoring the gating effect caused by the charges of the target proteins. Since the CNT-FET biosensors were used in buffer solution, it was crucial to use small-size receptors like aptamers than whole antibodies so that the charged target IgE could approach the CNT surface within the Debye length distance to give a large gating effect. The results show that CNT-FET biosensors using monoclonal IgE antibody had very low sensitivity (minimum detectable level 1000 ng/mL), while those based on anti-IgE aptamer could detect 50 ng/mL. Moreover, the aptamer-modified CNT-FET herein could successfully block non-target proteins and could selectively detect the target protein in an environment similar to human serum electrolyte. Therefore, aptamer-based CNT-FET devices enable the production of label-free ultrasensitive electronic biosensors to detect clinically important biomarkers for disease diagnosis.     

Ultrahigh‐Conductivity Polymer Hydrogels with Arbitrary Structures

A poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) hydrogel is prepared by thermal treatment of a commercial PEDOT:PSS (PH1000) suspension in 0.1 mol L^?1 sulfuric acid followed by partially removing its PSS component with concentrated sulfuric acid. This hydrogel has a low solid content of 4% (by weight) and an extremely high conductivity of 880 S m^?1. It can be fabricated into different shapes such as films, fibers, and columns with arbitrary sizes for practical applications. A highly conductive and mechanically strong porous fiber is prepared by drying PEDOT:PSS hydrogel fiber to fabricate a current‐collector‐free solid‐state flexible supercapacitor. This fiber supercapacitor delivers a volumetric capacitance as high as 202 F cm^?3 at 0.54 A cm^?3 with an extraordinary high‐rate performance. It also shows excellent electrochemical stability and high flexibility, promising for the application as wearable energy‐storage devices.     

An All‐Plastic Field‐Effect Nanofluidic Diode Gated by a Conducting Polymer Layer

The design of an all‐plastic field‐effect nanofluidic diode is proposed, which allows precise nanofluidic operations to be performed. The fabrication process involves the chemical synthesis of a conductive poly(3,4‐ethylenedioxythiophene) (PEDOT) layer over a previously fabricated solid‐state nanopore. The conducting layer acts as gate electrode by changing its electrochemical state upon the application of different voltages, ultimately changing the surface charge of the nanopore. A PEDOT‐based nanopore is able to discriminate the ionic species passing through it in a quantitative and qualitative manner, as PEDOT nanopores display three well‐defined voltage‐controlled transport regimes: cation‐rectifying, non‐rectifying, and anion rectifying regimes. This work illustrates the potential and versatility of PEDOT as a key enabler to achieve electrochemically addressable solid‐state nanopores. The synergism arising from the combination of highly functional conducting polymers and the remarkable physical characteristics of asymmetric nanopores is believed to offer a promising framework to explore new design concepts in nanofluidic devices.     

Electrostatic Limit of Detection of Nanowire‐Based Sensors

Scanning gate microscopy is used to determine the electrostatic limit of detection (LOD) of a nanowire (NW) based chemical sensor with a precision of sub‐elementary charge. The presented method is validated with an electrostatically formed NW whose active area and shape are tunable by biasing a multiple gate field‐effect transistor (FET). By using the tip of an atomic force microscope (AFM) as a local top gate, the field effect of adsorbed molecules is emulated. The tip induced charge is quantified with an analytical electrostatic model and it is shown that the NW sensor is sensitive to about an elementary charge and that the measurements with the AFM tip are in agreement with sensing of ethanol vapor. This method is applicable to any FET‐based chemical and biological sensor, provides a means to predict the absolute sensor performance limit, and suggests a standardized way to compare LODs and sensitivities of various sensors.     

An Individual Nanocube‐Based Plasmonic Biosensor for Real‐Time Monitoring the Structural Switch of the Telomeric G‐Quadruplex

Promoted by the localized surface plasmon resonance nanotechnology, a simple and sensitive plasmonic aptamer nanosensor (nanoaptasensor) on an individual Au@Ag core‐shell nanocube (Au@Ag NC) has been proposed for real‐time monitoring of the formation process of G‐quadruplex structures and label‐free analysis of potassium ions (K⁺). In particular, the analysis of the thermodynamic parameters indicates that there are two types of binding states accompanied with a remarkable change of free energy (ΔG) in the sequential folding process of telomere DNA sequence. This nanoaptasensor has raised promising applications in monitoring the dynamic process of the structural switch of the G‐quadruplex.     

High‐Performance Inverted Planar Perovskite Solar Cells Enhanced by Thickness Tuning of New Dopant‐Free Hole Transporting Layer

A new hole transporting material (HTM) named DMZ is synthesized and employed as a dopant‐free HTM in inverted planar perovskite solar cells (PSCs). Systematic studies demonstrate that the thickness of the hole transporting layer can effectively enhance the morphology and crystallinity of the perovskite layer, leading to low series resistance and less defects in the crystal. As a result, the champion power conversion efficiency (PCE) of 18.61% with J_SC = 22.62 mA cm^?2, V_OC = 1.02 V, and FF = 81.05% (an average one is 17.62%) is achieved with a thickness of ≈13 nm of DMZ (2 mg mL^?1) under standard global AM 1.5 illumination, which is ≈1.5 times higher than that of devices based on poly(3,4‐ethylenedioxythiophene)/poly(styrene sulfonic acid) (PEDOT:PSS). More importantly, the devices based on DMZ exhibit a much better stability (90% of maximum PCE retained after more than 556 h in air (relative humidity ≈ 45%–50%) without any encapsulation) than that of devices based on PEDOT:PSS (only 36% of initial PCE retained after 77 h in same conditions). Therefore, the cost‐effective and facile material named DMZ offers an appealing alternative to PEDOT:PSS or polytriarylamine for highly efficient and stable inverted planar PSCs.     

Design of Hierarchical Beads for Efficient Label‐Free Cell Capture

Defined hierarchical materials promise cell analysis and call for application‐driven design in practical use. The further issue is to develop advanced materials and devices for efficient label‐free cell capture with minimum instrumentation. Herein, the design of hierarchical beads is reported for efficient label‐free cell capture. Silica nanoparticles (size of ≈15 nm) are coated onto silica spheres (size of ≈200 nm) to achieve nanoscale surface roughness, and then the rough silica spheres are combined with microbeads (≈150–1000 µm in diameter) to assemble hierarchical structures. These hierarchical beads are built via electrostatic interaction, covalent bonding, and nanoparticle adherence. Further, after functionalization by hyaluronic acid (HA), the hierarchical beads display desirable surface hydrophilicity, biocompatibility, and chemical/structural stability. Due to the controlled surface topology and chemistry, HA‐functionalized hierarchical beads afford high cell capture efficiency up to 98.7% in a facile label‐free manner. This work guides the development of label‐free cell capture techniques and contributes to the construction of smart interfaces in bio‐systems.     

DNA Nanotweezers and Graphene Transistor Enable Label‐Free Genotyping

Electronic DNA‐biosensor with a single nucleotide resolution capability is highly desirable for personalized medicine. However, existing DNA‐biosensors, especially single nucleotide polymorphism (SNP) detection systems, have poor sensitivity and specificity and lack real‐time wireless data transmission. DNA‐tweezers with graphene field effect transistor (FET) are used for SNP detection and data are transmitted wirelessly for analysis. Picomolar sensitivity of quantitative SNP detection is achieved by observing changes in Dirac point shift and resistance change. The use of DNA‐tweezers probe with high‐quality graphene FET significantly improves analytical characteristics of SNP detection by enhancing the sensitivity more than 1000‐fold in comparison to previous work. The electrical signal resulting from resistance changes triggered by DNA strand‐displacement and related changes in the DNA geometry is recorded and transmitted remotely to personal electronics. Practical implementation of this enabling technology will provide cheaper, faster, and portable point‐of‐care molecular health status monitoring and diagnostic devices.     

Roll‐to‐Roll Production of Graphene Hybrid Electrodes for High‐Efficiency,Flexible Organic Photoelectronics

Despite nearly two decades of research, the absence of ideal, flexible, and transparent electrodes has been the biggest bottleneck for realizing flexible and printable electronics via roll‐to‐roll (R2R) method. A fabrication of poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate):graphene:ethyl cellulose (PEDOT:PSS:G:EC) hybrid electrodes by R2R process, which allows for the elimination of strong acid treatment. The high‐performance flexible printable electrode includes a transmittance (T) of 78% at 550 nm and a sheet resistance of 13 Ω sq⁻¹ with excellent mechanical stability. These features arise from the PSS interacting strongly with the ethyoxyl groups from EC promoting a favorable phase separation between PEDOT and PSS chains, and the highly uniform and conductive G:EC enable rearrangement of the PEDOT chains with more expanded conformation surrounded by G:EC via the π–π interaction between G:EC and PEDOT. The hybrid electrodes are fully functional as universal electrodes for outstanding flexible electronic applications. Organic solar cells based on the hybrid electrode exhibit a high power conversion efficiency of 9.4% with good universality for active layer. Moreover, the organic light‐emitting diodes and photodetector devices hold the same level to or outperform those based on indium tin oxide flexible transparent electrodes.     

Effects of Water and Different Solutes on Carbon‐Nanotube Low‐Voltage Field‐Effect Transistors

Semiconducting single‐walled carbon nanotubes (swCNTs) are a promising class of materials for emerging applications. In particular, they are demonstrated to possess excellent biosensing capabilities, and are poised to address existing challenges in sensor reliability, sensitivity, and selectivity. This work focuses on swCNT field‐effect transistors (FETs) employing rubbery double‐layer capacitive dielectric poly(vinylidene fluoride‐co‐hexafluoropropylene). These devices exhibit small device‐to‐device variation as well as high current output at low voltages (<0.5 V), making them compatible with most physiological liquids. Using this platform, the swCNT devices are directly exposed to aqueous solutions containing different solutes to characterize their effects on FET current–voltage (FET I–V) characteristics. Clear deviation from ideal characteristics is observed when swCNTs are directly contacted by water. Such changes are attributed to strong interactions between water molecules and sp²‐hybridized carbon structures. Selective response to Hg²⁺ is discussed along with reversible pH effect using two distinct device geometries. Additionally, the influence of aqueous ammonium/ammonia in direct contact with the swCNTs is investigated. Understanding the FET I–V characteristics of low‐voltage swCNT FETs may provide insights for future development of stable, reliable, and selective biosensor systems.     

Sustainable Solid‐State Supercapacitors Made of 3D‐Poly(3,4‐ethylenedioxythiophene) and κ‐Carrageenan Biohydrogel

3D‐Poly(3,4‐ethylenedioxythiophene) (PEDOT) electrodes are prepared using the multi‐step template‐assisted approach. Specifically, poly(lactic acid) nano‐ and microfibers collected on a previously polymerized PEDOT film are used as templates for PEDOT nano‐ and microtubes, respectively. Morphological analysis of the samples indicates that 3D‐PEDOT electrodes obtained using a low density of templates, in which nano‐ and microtubes are clearly identified, exhibit higher porosity, and specific surface than conventional 2D‐PEDOT electrodes. However, a pronounced leveling effect is observed when the density of templates is high. Thus, electrodes with microtubes still present a 3D‐morphology but much less marked than those prepared using a low density of PLA microfibers, whereas the morphology of those with nanotubes is practically identical to that of films. Electrochemical studies prove that solid supercapacitors prepared using 3D‐PEDOT electrodes and κ‐carrageenan biohydrogel as electrolytic medium, exhibit higher ability to exchange charge reversibly and to storage charge than the analogues prepared with 2D‐electrodes. Furthermore, solid devices prepared using 3D‐electrodes and κ‐carrageenan biohydrogel exhibit very similar specific capacitances that those obtained using the same electrodes and a liquid electrolyte (i.e., acetonitrile solution with 0.1 M LiClO₄). These results prove that the success of 3D‐PEDOT electrodes is independent of the electrolytic medium.

     

In-situ detection of C-reactive protein using silicon nanowire field effect transistor

Label-free, sensitive, and real-time c-reactive protein (CRP) sensor was fabricated using p-type silicon nanowire (SiNW) based structures configured as field effect transistors (FET) using the conventional 'top-down' semiconductor processes. The width of SiNWs were distributed 80 nm to 400 nm. Among them to improve signal-to-noise ratio and sensitivity of SiNW FET, 221 nm-SiNW was chosen for biosensing of CRP. Antibody of c-reactive protein (anti-CRP) was immobilized on the SiNW surface through polydimethylsiloxane (PDMS) microfluidic channel for detection of CRP. Specific binding of CRP with anti-CRP on the SiNW surface caused a conductance change of SiNW FET and various injections from 10 and 1 microg/ml to 100 ng/ml solutions of CRP resulted in the conductance changes from 39 and 25 to 16%, respectively. Label-free, in-situ and very sensitive electrical detection of CRP was demonstrated with the prepared SiNW FET.     

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Emerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H₂O₂ and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 10² mL^?1 and a linear response range from 4.8 × 10³ to 4.8 × 10⁶ exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.