Quantum‐Dot‐Functionalized Poly(styrene‐co‐acrylic acid) Microbeads: Step‐Wise Self‐Assembly,Characterization, and Applications for Sub‐femtomolar Electrochemical Detection of DNA Hybridization

A novel nanoparticle label capable of amplifying the electrochemical signal of DNA hybridization is fabricated by functionalizing poly(styrene‐co‐acrylic acid) microbeads with CdTe quantum dots. CdTe‐tagged polybeads are prepared by a layer‐by‐layer self‐assembly of the CdTe quantum dots (diameter = 3.07 nm) and polyelectrolyte on the polybeads (diameter = 323 nm). The self‐assembly procedure is characterized using scanning and transmission electron microscopy, and X‐ray photoelectron, infrared and photoluminescence spectroscopy. The mean quantum‐dot coverage is (9.54 ± 1.2) × 10³ per polybead. The enormous coverage and the unique properties of the quantum dots make the polybeads an effective candidate as a functionalized amplification platform for labelling of DNA or protein. Herein, as an example, the CdTe‐tagged polybeads are attached to DNA probes specific to breast cancer by streptavidin–biotin binding to construct a DNA biosensor. The detection of the DNA hybridization process is achieved by the square‐wave voltammetry of Cd²⁺ after the dissolution of the CdTe tags with HNO₃. The efficient carrier‐bead amplification platform, coupled with the highly sensitive stripping voltammetric measurement, gives rise to a detection limit of 0.52 fmol L^?1 and a dynamic range spanning 5 orders of magnitude. This proposed nanoparticle label is promising, exhibits an efficient amplification performance, and opens new opportunities for ultrasensitive detection of other biorecognition events.     

Biosensor Array of Interpenetrating Polymer Network with Photonic Film Templated from Reactive Cholesteric Liquid Crystal and Enzyme‐Immobilized Hydrogel Polymer

A biosensor array is fabricated using an interpenetrating polymer network consisting of photonic film templated from reactive cholesteric liquid crystal (CLC) and enzyme‐immobilized polyacrylic acid (PAA). The solid‐state photonic film on the glass substrate is successfully templated by ultraviolet (UV) curing of the reactive CLC mixture of a reactive mesogen mixture of RMM 727 (from Merck) and a nonreactive chiral dopant of (S)‐4‐cyano‐4′‐(2‐methylbutyl)biphenyl following the extraction of the chiral dopant. The acrylic acid monomer mixed with a cross‐linker of tri(propylene glycol) diacrylate is infiltrated into the extracted space of the photonic film, and UV‐cured with a photomask to obtain a patterned array‐dot film. The interpenetrated cholesteric liquid crystal/hydrogel polymer network (CLC‐hydrogel‐IPN) array is further functionalized in the individual dots with urease, for a model study of biosensor array applications. The dots of the CLC‐hydrogel‐IPN array respond independently to the urea by a color change with high sensitivity and stability. Thus, the patterned CLC‐hydrogel‐IPN can be used as a new biosensor array for cost‐effective and easy visual detection without any sophisticated instruments.     

Ultrasensitive Detection of Mitochondrial DNA Mutation by Graphene Oxide/DNA Hydrogel Electrode

Ultrasensitive detection of nucleic acid has attracted considerable attention recently in academic research and clinic diagnostics. Current approaches for DNA analysis involve complicated or expensive processes for labeling and often yield a high detection limit. In this study, a hydrogel electrode prepared from graphene oxide and fish sperm DNA is used for label?free mitochondrial DNA detection by impedimetric approach. The hydrogel has a bionic structure containing rich water and natural biomolecule fish sperm DNA that would benefit the adsorption and hybridization of DNA. Graphene oxide is a semiconductor and its conductivity can be improved by doping negatively charged DNA molecules. The result shows that the conductivity and impedance change of hydrogel electrode could be tuned by its length and component. The linear range for DNA detection by the optimized hydrogel is from 1.0 × 10^?9 to 1.0 × 10^?20 M with a detection limit of 1.0 × 10^?20 M. The result is ascribed to the bionic structure and tunable conductivity of hydrogel electrode. The hydrogel electrode has been used to detect the real DNA samples from patients of ovarian cancer with satisfactory results.     

A Universal,Label‐Free,and Sensitive Optical Enzyme‐Sensing System for Nuclease and Methyltransferase Activity Based on Light Scattering of Carbon Nanotubes

A label‐free, enzyme‐responsive nanosystem that uses a DNA/single‐walled carbon nanotube (SWNT) assembly as the substrate is demonstrated for the sensitive, universal detection of restriction and nonrestriction endonucleases as well as methyltransferases in a homogeneous solution on the basis of light scattering (LS) of carbon nanotubes. This protocol is based on the different binding affinities of SWNTs to single‐ and double‐stranded DNA. This difference can lead to different LS signals that can be used for the detection of nuclease cleavage activity. The assay only requires a label‐free oligonucleotide probe, significantly reducing the typical cost. The LS technique and the use of a nuclease‐specific oligonucleotide probe impart extraordinarily high sensitivity and selectivity. This light scattering assay is universal and label‐free with a detection limit of 5 × 10^?6 U μL^?1 for S1 nuclease, 1 × 10^?4 U μL^?1 for EcoRI endonuclease, and 1 × 10^?2 U μL^?1 for EcoRI methylase. In principle, this assay can be used to detect any kind of nuclease by simply changing the DNA sequences of the specific probe.     

DNA‐Templated Magnetic Nanoparticle‐Quantum Dot Polymers for Ultrasensitive Capture and Detection of Circulating Tumor Cells

Circulating tumor cell (CTC) enumeration and analysis has emerged as an important platform for cancer diagnosis and prognosis. A great challenge, however, is to efficiently capture low abundant CTCs with high purity from blood samples in a rapid and high‐throughput manner for accurate and sensitive CTC detection. Herein, a new class of DNA‐templated magnetic nanoparticle‐quantum dot (QD)‐aptamer copolymers (MQAPs) is developed for rapid magnetic isolation of CTCs from human blood with high capture efficiency and purity approaching 80%. The phenotype of CTCs is simultaneously profiled with QD photoluminescence (PL) at single cell level. These MQAPs are constructed through hybridization chain reaction to achieve amplified magnetic response, extraordinary binding selectivity for target cells over background cells, and ultra bright ensemble QD PL for single cell detection. MQAPs are free from nonspecific binding that would otherwise compromise the capture purity of target cells. As a result, facile isolation and enumeration of rare CTCs in blood samples could be achieved in 20 min with high sensitivity and accuracy.     

Cationic Polyelectrolyte Amplified Bead Array for DNA Detection with Zeptomole Sensitivity and Single Nucleotide Polymorphism Selectivity

A highly sensitive strand specific DNA assay, which consists of a peptide nucleic acid (PNA) probe, a cationic conjugated polymer ( PFVP ), and self‐assembled polystyrene beads in microwell arrays on silicon chip, is reported. PFVP , as an efficient signal amplifier and signal reporter, has been specially designed and synthesized to be compatible with commercial confocal microscopes for sensing on solid substrates. The assay operates on the net increase in negative charge at the PNA surface that occurs upon single‐stranded DNA hybridization, which subsequently allows complex formation with the positively charged PFVP to favor energy transfer between the polymer and Cy5‐labeled target. With maximized surface contact provided by bead arrays and signal amplification provided by PFVP , this assay allows detection of ～300 copies of Cy5‐labeled DNA using a commercial confocal microscope. In addition, the same strategy is also extended for label‐free DNA detection with a detection sensitivity of 150 attomole. Excellent discrimination against single nucleotide polymorphism (SNP) is also demonstrated for both Cy5‐labeled and label‐free target detection. This study indicates that cationic conjugated polymers have great potential to be incorporated into the widely used microarray technology for simplified process with improved detection sensitivity.     

Detection of Glioma‐Derived Exosomes with the Biotinylated Antibody‐Functionalized Titanium Nitride Plasmonic Biosensor

Titanium nitride (TiN), as an excellent alternative plasmonic supporting material compared to gold and silver, exhibits tunable plasmonic properties in the visible and near‐infrared spectra. However, label‐free surface plasmon resonance biosensing with TiN is seldom reported due to lack of proper surface functionalization protocols. Herein, this study reports biotinylated antibody‐functionalized TiN (BAF‐TiN) for high‐performance label‐free biosensing applications. The BAF‐TiN biosensor can quantitatively detect exosomes of 30–200 nm extracellular vesicles, isolated from a human glioma cell line. The limit of detection for an exosomal membrane protein with the BAF‐TiN biosensor is found to be 4.29 × 10^?3µg mL^?1 for CD63, an exosome marker, and 2.75 × 10^?3µg mL^?1 for epidermal growth factor receptor variant‐III, a glioma specific mutant protein, respectively. In conclusion, combining the biocompatibility, high stability, and excellent label‐free sensing performance of TiN, the BAF‐TiN biosensor could have great potential for the detection of cancer biomarkers, including exosomal surface proteins.     

A One‐Kilobit PQR‐CMOS Smart Pixel Array

The photonic quantum ring (PQR) laser is a three dimensional whispering gallery (WG) mode laser and has anomalous quantum wire properties, such as microampere to nanoampere range threshold currents and √T‐dependent thermal red shifts. We observed uniform bottom emissions from a 1‐kb smart pixel chip of a 32×32 InGaAs PQR laser array flip‐chip bonded to a 0.35 µm CMOS‐based PQR laser driver. The PQR‐CMOS smart pixel array, now operating at 30 MHz, will be improved to the GHz frequency range through device and circuit optimization.     

Soft‐Lithographed Up‐Converted Distributed Feedback Visible Lasers Based on CdSe–CdZnS–ZnS Quantum Dots

The development of a solution‐deposited up‐converted distributed feedback laser prototype is presented. It employs a sol–gel silica/germania soft‐lithographed microcavity and CdSe–CdZnS–ZnS quantum dot/sol–gel zirconia composites as optical gain material. Characterization of the linear and nonlinear optical properties of quantum dots establishes their high absorption cross‐sections in the one‐ and two‐ photon absorption regimes to be 1 × 10^?14 cm² and 5 × 10⁴ GM, respectively. In addition, ultrafast transient absorption dynamics measurements of the graded seal quantum dots reveal that the Auger recombination lifetime is 220 ps, a value two times higher than that of the corresponding CdSe core. These factors enable the use of such quantum dots as optically pumped gain media, operating in the one‐ and two‐photon absorption regime. The incorporation of CdSe–CdZnS–ZnS quantum dots within a zirconia host matrix affords a quantum‐dot ink that can be directly deposited on our soft‐lithographed distributed feedback grating to form an all‐solution‐processed microcavity laser.     

User‐Friendly Universal and Durable Subcellular‐Scaled Template for Protein Binding: Application to Single‐Cell Patterning

A new method for subcellular‐sized protein patterning on a SiOx substrate is demonstrated by dip‐pen nanolithography printed aldehyde‐terminated alkylsilane template. The aldehyde‐silane template is stable and durable; for example, subcellular scaled IgG protein array can be obtained using one‐year old aldehyde‐silane template. Moreover, single cell patterning is successfully carried out by extracellular material (ECM) protein microarray and nanoarray fabricated on an aldehyde‐silane template. With more than half of chance, single‐ or double‐cells are successfully attached on fibronectin protein nanoarrays in 21 × 21 μm ² (7 × 7 dot array) and 42 × 42 μm² (14 × 14 dot array). The fibronectin nanoarray with small area (21 × 21 μm²) shows the more rate of single cell attachment. Therefore, it is also demonstrated that cell patterning can be controlled by adjusting the nanostructure of ECM materials.     

Ultra‐Adaptable and Wearable Photonic Skin Based on a Shape‐Memory,Responsive Cellulose Derivative

Photonic skins enable a direct and intuitive visualization of various physical and mechanical stimuli with eye‐readable colorations by intimately laminating to target substrates. Their development is still at infancy compared to that of electronic skins. Here, an ultra‐adaptable, large‐area (10 × 10 cm²), multipixel (14 × 14) photonic skin based on a naturally abundant and sustainable biopolymer of a shape‐memory, responsive multiphase cellulose derivative is presented. The wearable, multipixel photonic skin mainly consists of a photonic sensor made of mesophase cholesteric hydroxypropyl cellulose and an ultra‐adaptable adhesive layer made of amorphous hydroxypropyl cellulose. It is demonstrated that with multilayered flexible architectures, the multiphase cellulose derivative–based integrated photonic skin can not only strongly couple to a wide range of biological and engineered surfaces, with a maximum of ≈180 times higher adhesion strengths compared to those of the polydimethylsiloxane adhesive, but also directly convert spatiotemporal stimuli into visible color alterations in the large‐area, multipixel array. These colorations can be simply converted into 3D strain mapping data with digital camera imaging.     

Ultrasensitive Specific Stimulant Assay Based on Molecularly Imprinted Photonic Hydrogels

Taking theophylline and (1R,2S)‐(−)‐ephedrine as template molecules, two imprinted photonic‐hydrogel films are prepared by a combination of colloidal‐crystal and molecular‐imprinting techniques. This paper shows a new approach for rapid and handy stimulant detection with high sensitivity and specificity. One film is proposed for analogous molecule assay, another one for chiral recognition. The key point of this approach is that the imprinted photonic polymer (IPP) consists of a three‐dimensional (3D), highly‐ordered and interconnected macroporous array with a thin hydrogel wall, where nanocavities complementary to analytes in shape and binding sites are distributed. This special, bicontinuous, hierarchical structure enables this polymer to report quickly, easily, sensitively and directly a molecular recognition event without any transducers and treatments for analytes (label‐free). The inherent affinity of the nanocavities, deriving from molecular imprinting, makes these sensors highly specific to analytes, even if in a competitive environment. Their sensitive and specific responses to stimulants in buffer are determined by Bragg diffractive shifts due to the lattice change of their 3D ordered macroporous arrays resulting from their preferential rebinding to the target molecules. The measurements show that the prepared hydrogel films exhibit high sensitivity in such a 0.1 fM concentration of analytes and specificity even in a competitive urinous buffer. The reported method provides a rapid and handy approach for stimulant assay and drug analysis in athletic sports.     

Integration of a Chemical‐Responsive Hydrogel into a Porous Silicon Photonic Sensor for Visual Colorimetric Readout

The incorporation of a chemo‐responsive hydrogel into a 1D photonic porous silicon (PSi) transducer is demonstrated. A versatile hydrogel backbone is designed via the synthesis of an amine‐functionalized polyacrylamide copolymer where further amine‐specific biochemical reactions can enable control of cross‐links between copolymer chains based on complementary target–probe systems. As an initial demonstration, the incorporation of disulfide chemistry to control cross‐linking of this hydrogel system within a PSi Bragg mirror sensor is reported. Direct optical monitoring of a characteristic peak in the white light reflectivity spectrum of the incorporated PSi Bragg mirror facilitates real‐time detection of the hydrogel dissolution in response to the target analyte (reducing agent) over a timescale of minutes. The hybrid sensor response characteristics are shown to systematically depend on hydrogel cross‐linking density and applied target analyte concentration. Additionally, effects due to responsive hydrogel confinement in a porous template are shown to depend on pore size and architecture of the PSi transducer substrate. Sufficient copolymer and water is removed from the PSi transducer upon dissolution and drying of the hydrogel to induce color changes that can be detected by the unaided eye. This highlights the potential for future development for point‐of‐care diagnostic biosensing.     

Photochemically Controlled Photonic Crystals

We have developed photochemically controlled photonic crystals that may be useful in novel recordable and erasable memories and/or display devices. These materials can operate in the UV, visible, or near‐IR spectral regions. Information is recorded and erased by exciting the photonic crystal with ～ 360 nm UV light or ～ 480 nm visible light. The information recorded is read out by measuring the photonic crystal diffraction wavelength. The active element of the device is an azobenzene‐functionalized hydrogel, which contains an embedded crystalline colloidal array. UV excitation forms cis‐azobenzene while visible excitation forms trans‐azobenzene. The more favorable free energy of mixing of cis‐azobenzene causes the hydrogel to swell and to red‐shift the photonic crystal diffraction. We also observe fast nanosecond, microsecond, and millisecond transient dynamics associated with fast heating lattice constant changes, refractive index changes, and thermal relaxations.     

Conjugated Polymers Combined with a Molecular Beacon for Label‐Free and Self‐Signal‐Amplifying DNA Microarrays

A conjugated polymer (CP) and molecular‐beacon‐based solid‐state DNA sensing system is developed to achieve sensitive, label‐free detection. A novel conjugated poly(oxadiazole) derivative exhibiting amine and thiol functional groups ( POX‐SH ) is developed for unique chemical and photochemical stability and convenient solid‐state on‐chip DNA synthesis. POX‐SH is soluble in most nonpolar organic solvents and exhibits intense blue fluorescence. POX‐SH is covalently immobilized onto a maleimido‐functionalized glass slide by means of its thiol group. Molecular beacons having a fluorescent dye or quencher molecule as the fluorescence resonance energy transfer (FRET) acceptor are synthesized on the immobilized POX‐SH layer through direct on‐chip oligonucleotide synthesis using the amine side chain of POX‐SH . Selective hybridization of the molecular beacon probes with the target DNA sequence opens up the molecular beacon probes and affects the FRET between POX‐SH and the dye or quencher, producing a sensitive and label‐free fluorescence sensory signal. Various molecular design parameters, such as the size of the stem and loop of the molecular beacon, the choice of dye, and the number of quencher molecules are systematically controlled, and their effects on the sensitivity and selectivity are investigated.     

Bioinspired Micropatterned Superhydrophilic Au‐Areoles for Surface‐Enhanced Raman Scattering (SERS) Trace Detection

Surface‐enhanced Raman scattering (SERS) provides an approach for the label‐free and miniaturized detection of the trace amount of analyte molecules. A SERS microchip of Au‐areoles array, mimicking the areole on the cactus, is facilely and controllably prepared through selectively electrochemical deposition on patterned superhydrophilic–superhydrophobic substrates. The Au‐areoles are full of SERS hot spots thanks to the large amounts of sharp edges, tips, and coupled branches. Meanwhile, the superhydrophilic sites on the superhydrophobic substrate can collect the target molecules into those hot spots. The combination of the SERS enhancement of the nanostructured‐Au and the collective effect of the superhydrophilic–superhydrophobic pattern endows the microchip with sample‐effective, ultrasensitive, and efficient Raman detection capabilities, which are demonstrated by integrated detection of femtomol Rhodamine 6G and diverse bioanalytes. The chip can also be used for mutually independent multisample detection without interference.     

Light‐Induced Swelling‐Responsive Conductive,Adhesive, and Stretchable Wireless Film Hydrogel as Electronic Artificial Skin

Light‐induced wireless soft electronic skin hydrogels with excellent mechanical and electronic properties are important for several applications, such as soft robotics and intelligent wearable devices. Precise control of reversible stretchability and capacitive properties depending on intermolecular interaction and surface characteristics remains a challenge. Here, a thin‐film hydrogel is designed based on titanium oxide (TiO₂) polydopamine–perfluorosilica carbon dot‐conjugated chitosan–polyvinyl alcohol‐loaded tannic acid with controllable hydrophobic–hydrophilic transition in the presence of UV–vis light irradiation. The shifting of surface wettability from hydrophobic to hydrophilic by irradiation affects thin‐film water permeability and swelling ratio. This allows the penetration of water into the matrix to change its mechanical strength, electronic properties, and adhesive behavior. Specifically, the hydrogel displays mechanical strain as high as 278% in response to light stimuli and demonstrates the ability to regain its initial state determining the elasticity of the fabricated material. Moreover, the thin‐film hydrogel shows an increase in conductivity to 1.096 × 10^?3 and 1.026 × 10^?3 S cm^?1 when irradiated with UV and visible light, respectively. The hydrogel exhibits capacitive reversibility that follows finger motion which can be identified directly or remotely using wireless connection, indicative of its possible applications as an artificial electronic skin.     

High‐Density Periodically Ordered Magnetic Cobalt Ferrite Nanodot Arrays by Template‐Assisted Pulsed Laser Deposition

A novel nanopatterning method using pulsed laser deposition through an ultrathin anodic aluminium oxide (AAO) membrane mask is proposed to synthesize well‐ordered nanodot arrays of magnetic CoFe₂O₄ that feature a wide range of applications like sensors, drug delivery, and data storage. This technique allows the adjustment of the array dimension from ～35 to ～300 nm in diameter and ～65 to ～500 nm in inter‐dot distance. The dot density can be as high as 0.21 Terabit in.^?2. The microstructure of the nanodots is characterized by SEM, TEM, and XRD and their magnetic properties are confirmed by well‐defined magnetic force microscopy contrasts and by hysteresis loops recorded by a superconducting quantum interference device. Moreover, the high stability of the AAO mask enables the epitaxial growth of nanodots at a temperature as high as 550 °C. The epitaxial dots demonstrate unique complex magnetic domains such as bubble and stripe domains, which are switchable by external magnetic fields. This patterning method creates opportunities for studying novel physics in oxide nanomagnets and may find applications in spintronic devices.     

In Vivo Imaging of Composite Hydrogel Scaffold Degradation Using CEST MRI and Two‐Color NIR Imaging

Hydrogel scaffolding of stem cells is a promising strategy to overcome initial cell loss and manipulate cell function post‐transplantation. Matrix degradation is a requirement for downstream cell differentiation and functional tissue integration, which determines therapeutic outcome. Therefore, monitoring of hydrogel degradation is essential for scaffolded cell replacement therapies. It is shown here that chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) can be used as a label‐free imaging platform for monitoring the degradation of crosslinked hydrogels containing gelatin (Gel) and hyaluronic acid (HA), of which the stiffness can be fine‐tuned by varying the ratio of the Gel:HA. By labeling Gel and HA with two different near‐infrared (NIR) dyes having distinct emission frequencies, it is shown here that the HA signal remains stable for 42 days, while the Gel signal gradually decreases to <25% of its initial value at this time point. Both imaging modalities are in excellent agreement for both the time course and relative value of CEST MRI and NIR signals (R² = 0.94). These findings support the further use of CEST MRI for monitoring biodegradation and optimizing of gelatin‐containing hydrogels in a label‐free manner.     

High‐Efficiency and Stable Quantum Dot Light‐Emitting Diodes Enabled by a Solution‐Processed Metal‐Doped Nickel Oxide Hole Injection Interfacial Layer

Stabilization is one critical issue that needs to be improved for future application of colloidal quantum dot (QD)‐based light‐emitting diodes (QLEDs). This study reports highly efficient and stable QLEDs based on solution‐processsed, metal‐doped nickel oxide films as hole injection layer (HIL). Several kinds of metal dopants (Li, Mg, and Cu) are introduced to improve the hole injection capability of NiO films. The resulting device with Cu:NiO HIL exhibits superior performance compared to the state‐of‐the‐art poly(3,4‐ethylenedioxythiophene):poly(styrene‐sulfonate) (PEDOT:PSS)‐based QLEDs, with a maximum current efficiency and external quantum efficiency of 45.7 cd A^?1 and 10.5%, respectively. These are the highest values reported so far for QLEDs with PEDOT:PSS‐free normal structure. Meanwhile, the resulting QLED shows a half‐life time of 87 h at an initial luminance of 5000 cd m^?2, almost fourfold longer than that of the PEDOT:PSS‐based device.