DNA liquid crystals with AIE effect toward humidity-indicating biomaterials.

In this study, by fabricating DNA doped with tetraphenylethene-containing ammonium surfactant, the resulting solvent-free DNA ionic complex could undergo a humidity-induced phase change that could be well tracked by the fluorescence signal of the surfactant. Taking advantage of the humidity-induced change in fluorescence, the reported ionic DNA complex could accurately indicate the humidity in real time.

Plasmonic Gold Nanostar-Based Probes with Distance-Dependent Plasmon-Enhanced Fluorescence for Ultrasensitive DNA Methyltransferase Assay.

The ultrasensitive DNA methyltransferase (Dam MTase) assay is of high significance for biomedical research and clinical diagnosis because of its profound effect on gene regulation. However, detection sensitivity is still limited by shortcomings, including photobleaching and weak signal intensities of conventional fluorophores at low concentrations. Plasmonic nanostructures with ultrastrong electromagnetic fields and fluorescence enhancement capability that can overcome these intrinsic defects hold great potential for ultrasensitive bioanalysis. Herein, a silica-coated gold nanostars (Au NSTs@SiO2)-based plasmon-enhanced fluorescence (PEF) probe with 20 "hot spots" was developed for ultrasensitive detection of Dam MTase. Here, the Dam Mtase assay was achieved by detecting the byproduct PPi of the rolling circle amplification reaction. It is worth noting that, benefiting from the excellent fluorescence enhancement capability of Au NSTs originating from their 20 "hot spots", the detection limit of Dam Mtase was reduced by nearly 105 times. Moreover, the proposed Au NST-based PEF probe enabled versatile evaluation of Dam MTase inhibitors as well as endogenous Dam MTase detection in GW5100 and JM110 Escherichia coli cell lysates, demonstrating its potential in biomedical analysis.

Enhanced split-type photoelectrochemical aptasensor incorporating a robust antifouling coating derived from four-armed polyethylene glycol.

Antifouling biosensors capable of preventing protein nonspecific adhesion in real human bodily fluids are highly sought-after for precise disease diagnosis and treatment. In this context, an enhanced split-type photoelectrochemical (PEC) aptasensor was developed incorporating a four-armed polyethylene glycol (4A-PEG) to construct a robust antifouling coating, enabling accurate and sensitive bioanalysis. The split-type PEC system involved the photoelectrode and the biocathode, effectively separating signal converter with biorecogniton events. Specifically, the TiO2 electrode underwent sequential modification with ZnIn2S4 (ZIS) and polydopamine (PDA) to form the PDA/ZIS/TiO2 photoelectrode. The cathode substrate was synthesized as a hybrid of N-doped graphene loaded with Pt nanoparticles (NG-Pt), and subsequently modified with 4A-PEG to establish a robust antifouling coating. Following the anchoring of probe DNA (pDNA) on the 4A-PEG-grafted antifouling coating, the biocathode for model target of cancer antigen 125 (CA125) was obtained. Leveraging pronounced photocurrent output of the photoelectrode and commendable antifouling characteristics of the biocathode, the split-type PEC aptasensor showcased exceptional detection performances with high sensitivity, good selectivity, antifouling ability, and potential feasibility.

Renin imprinted Poly(methyldopa) for biomarker detection and disease therapy.

Conventional molecularly imprinted polymers (MIPs) perform their functions principally depended on their three dimensional (3D) imprinted cavities (recognition sites) of templates. Here, retaining the function of recognition sites resulted from the imprinting of template molecules, the role of functional monomers is explored and expanded. Briefly, a class of dual-functional renin imprinted poly(methyldopa) (RMIP) is prepared, consisting of a drug-type function monomer (methyldopa, clinical high blood pressure drug) and a corresponding disease biomarker (renin, biomarker for high blood pressure disease). To boost target-to-receptor binding ratio and sensitivity, the microstructure of recognition sites is beforehand calculated and designed by Density Functional Theory calculations, and the whole interfacial structure, property and thickness of RMIP film is regulated by adjusting the polymerization techniques. The dual-functional applications of RMIP for biomarker detection and disease therapy in vivo is explored. Such RMIP-based biosensors achieves highly sensitive biomarker detection, where the LODs reaches down to 1.31 × 10-6 and 1.26 × 10-6 ng mL-1 for electrochemical and chemical polymers, respectively, and the application for disease therapy in vivo has been verified where displays the obviously decreased blood pressure values of mice. No acute and long-term toxicity is found from the pathological slices, declaring the promising clinical application potential of such engineered RMIP nanostructure.

Robust Electrochemical Biosensors Based on Antifouling Peptide Nanoparticles for Protein Quantification in Complex Biofluids.

Peptides with distinct physiochemical properties and biocompatibility hold significant promise across diverse domains including antifouling biosensors. However, the stability of natural antifouling peptides in physiological conditions poses significant challenges to their viability for sustained practical applications. Herein, a unique antifouling peptide FFFGGGEKEKEKEK was designed and self-assembled to form peptide nanoparticles (PNPs), which possessed enhanced stability against enzymatic hydrolysis in biological fluids. The PNP-coated interfaces exhibited superior stability and antifouling properties in preventing adsorption of nonspecific materials, such as proteins and cells in biological samples. Moreover, a highly sensitive and ultralow fouling electrochemical biosensor was developed through the immobilization of the PNPs and specific aptamers onto the polyaniline nanowire-modified electrode, achieving the biomarker carcinoembryonic antigen detection in complex biofluids with reliable accuracy. This research not only addresses the challenge of the poor proteolytic resistance observed in natural peptides but also introduces a universal strategy for constructing ultralow fouling sensing devices.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Antifouling strategies for electrochemical sensing in complex biological media.

Surface fouling poses a significant challenge that restricts the analytical performance of electrochemical sensors in both in vitro and in vivo applications. Biofouling resistance is paramount to guarantee the reliable operation of electrochemical sensors in complex biofluids (e.g., blood, serum, and urine). Seeking efficient strategies for surface fouling and establishing highly sensitive sensing platforms for applications in complex media have received increasing attention in the past. In this review, we provide a comprehensive overview of recent research efforts focused on antifouling electrochemical sensors. Initially, we present a detailed illustration of the concept about biofouling along with an exploration of four key antifouling mechanisms. Subsequently, we delve into the commonly employed antifouling strategies in the fabrication of electrochemical sensors. These encompass physical surface topography (micro/nanostructure coatings and filtration membranes) and chemical surface modifications (PEG and its derivatives, zwitterionic polymers, peptides, proteins, and various other antifouling materials). The progress in antifouling electrochemical sensors is proposed concerning the antifouling mechanisms as well as sensing capability assessments (e.g., sensitivity, stability, and practical application ability). Finally, we summarize the evolving trends in the field and highlight some key remaining limitations.

A stretchable wearable sensor with dual working electrodes for reliable detection of uric acid in sweat.

Wearable sweat sensors with stretch capabilities and robust performances are desired for continuous monitoring of human health, and it remains a challenge for sweat sensors to detect targets reliably in both static and dynamic states. Herein, a flexible sweat sensor was created using a cost-effective approach involving the utilization of three-dimensional graphene foam and polydimethylsiloxane (PDMS). The flexible electrochemical sensor was fabricated based on PDMS and Pt/Pd nanoparticles modified 3D graphene foam for the detection of uric acid in sweat. Pt/Pd nanoparticles were electrodeposited on the graphene foam to markedly enhance the electrocatalytic activity for uric acid detection. The graphene foam with excellent electrical property and high porosity, and PDMS with an ideal mechanical property endow the sensing device with high stretchability (tolerable strain up to 110 %), high sensitivity (0.87 µA µM-1 cm-2), and stability (remaining unchanged for more than 5000 cycles) for daily wear. To eliminate possible interferences, the wearable sensor was designed with dual working electrodes, and their response difference ensured reliable and accurate detection of targets. This strategy of constructing sweat sensors with dual working electrodes based on the flexible composite material represents a promising way for the development of robust wearable sensing devices.

Light and endogenous enzyme triggered plasmonic antennas for accurate subcellular molecular imaging with enhanced spatial resolution.

Developing accurate tumor-specific molecular imaging approaches holds great potential for evaluating cancer progression. However, traditional molecular imaging approaches still suffer from restricted tumor specificity due to the "off-tumor" signal leakage. In this work, we proposed light and endogenous APE1-triggered plasmonic antennas for accurate tumor-specific subcellular molecular imaging with enhanced spatial resolution. Light activation ensures subcellular molecular imaging and endogenous enzyme activation ensures tumor-specific molecular imaging. In addition, combined with the introduction of plasmon enhanced fluorescence (PEF), off-tumor signal leakage at the subcellular level was effectively reduced, resulting in the significantly enhanced discrimination ratio of tumor/normal cells (∼11.57-fold) which is better than in previous reports, demonstrating great prospects of these plasmonic antennas triggered by light and endogenous enzymes for tumor-specific molecular imaging at the subcellular level.

Enhanced Hydroxyl Adsorption in Ultrathin NiO/Cr2 O3 In-Plane Heterostructures for Efficient Alkaline Methanol Oxidation Reaction.

The exploration of advanced nickel-based electrocatalysts for alkaline methanol oxidation reaction (MOR) holds immense promise for value-added organic products coupled with hydrogen production, but still remain challenging. Herein, we construct ultrathin NiO/Cr2 O3 in-plane heterostructures to promote the alkaline MOR process. Experimental and theoretical studies reveal that NiO/Cr2 O3 in-plane heterostructures enable a favorable upshift of the d-band center and enhanced adsorption of hydroxyl species, leading to accelerated generation of active NiO(OH)ads species. Furthermore, ultrathin in-plane heterostructures endow the catalyst with good charge transfer ability and adsorption behavior of methanol molecules onto catalytic sites, contributing to the improvement of alkaline MOR kinetics. As a result, ultrathin NiO/Cr2 O3 in-plane heterostructures exhibit a remarkable MOR activity with a high current density of 221 mA cm-2 at 0.6 V vs Ag/AgCl, which is 7.1-fold larger than that of pure NiO nanosheets and comparable with other highly active catalysts reported so far. This work provides an effectual strategy to optimize the activity of nickel-based catalysts and highlights the dominate efficacy of ultrathin in-plane heterostructures in alkaline MOR.

Phospholipid Bilayer Integrated with Multifunctional Peptide for Ultralow-Fouling Electrochemical Detection of HER2 in Human Serum.

Electrochemical biosensing devices face challenges of severe nonspecific adsorption in complex biological matrices for the detection of biomarkers, and thus, there is a significant need for sensitive and antifouling biosensors. Herein, a sensitive electrochemical biosensor with antifouling and antiprotease hydrolysis ability was constructed for the detection of human epidermal growth factor receptor 2 (HER2) by integrating multifunctional branched peptides with distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) self-assembled bilayer. The peptide was designed to possess antifouling, antiprotease hydrolysis, and HER2 recognizing capabilities. Molecular dynamics simulations demonstrated that the DSPE was able to effectively self-assemble into a bilayer, and the water contact angle and electrochemical experiments verified that the combination of peptide with the DSPE-PEG bilayer was conducive to enhancing the hydrophilicity and antifouling performance of the modified surface. The constructed HER2 biosensor exhibited excellent antifouling and antiprotease hydrolysis capabilities, and it possessed a linear range of 1.0 pg mL-1 to 1.0 µg mL-1, and a limit of detection of 0.24 pg mL-1. In addition, the biosensor was able to detect HER2 in real human serum samples without significant biofouling, and the assaying results were highly consistent with those measured by the enzyme-linked immunosorbent assay (ELISA), indicating the promising potential of the antifouling biosensor for clinical diagnosis.

Designed Polyhydroxyproline Helical Peptide with Ultrarobust Antifouling Capability for Electrochemical Sensing in Diverse Complex Biological Fluids.

Developing a generalized strategy for the nonfouling detection of biomarkers in diverse biological fluids presents a significant challenge. Herein, a polyhydroxyproline helical peptide (PHHP) was designed and adopted to fabricate electrochemical microsensors capable of detecting targets in various biological media. The PHHP possessed unique properties such as strong hydrophilicity, rigid structure, and lack of ionizable side-chain groups. Compared with common zwitterionic peptides (ZIPs), the PHHP exhibited similar antifouling capability but exceptional stability, allowing its antifouling performance to be unaffected by environmental alteration. The PHHP can prevent biofouling even in fluctuating pH conditions, high ionic strength environments, and the presence of high-valence ions and resist the protease hydrolysis. The PHHP-modified carbon fiber microelectrode was further immobilized with an aptamer to construct an antifouling microsensor for cortisol detection across diverse biofluids, and the microsensor exhibited acceptable accuracy and higher sensitivity than the ELISA method. In addition, different biological samples of mice were collected in situ using a microsensing device, and cortisol levels were analyzed in each specifically tailored region. This nonfouling sensing strategy based on PHHP allows a comprehensive assessment of biomarkers in both spatial and temporal dimensions in diverse biological environments, holding promising potential for early disease diagnosis and real-time health monitoring.

The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair.

Elastin-like polypeptides (ELPs) are thermally responsive biopolymers derived from natural elastin. These peptides have a low critical solution temperature phase behavior and can be used to prepare stimuli-responsive biomaterials. Through genetic engineering, biomaterials prepared from ELPs can have unique and customizable properties. By adjusting the amino acid sequence and length of ELPs, nanostructures, such as micelles and nanofibers, can be formed. Correspondingly, ELPs have been used for improving the stability and prolonging drug-release time. Furthermore, ELPs have widespread use in tissue repair due to their biocompatibility and biodegradability. Here, this review summarizes the basic property composition of ELPs and the methods for modulating their phase transition properties, discusses the application of drug delivery system and tissue repair and clarifies the current challenges and future directions of ELPs in applications.

An anti-fouling wearable molecular imprinting sensor based on semi-interpenetrating network hydrogel for the detection of tryptophan in sweat.

The challenge of heavy biofouling in complex sweat environments limits the potential of electrochemical sweat sensors for noninvasive physiological assessment. In this study, a novel semi-interpenetrating hydrogel of PSBMA/PEDOT:PSS was engineered by interlacing PEDOT:PSS conductive polymer with zwitterionic PSBMA network. This versatile hydrogel served as the foundation for developing an anti-fouling wearable molecular imprinting sensor capable of sensitive and robust detection of tryptophan (Trp) in complex sweat. The incorporation of PEDOT:PSS conductive polymer into the semi-interpenetrating hydrogel introduced diverse physical crosslinks, including hydrogen bonding, electrostatic interactions, and chain entanglement. This incorporation considerably boosted the hydrogel's mechanical robustness and imparted commendable self-healing property. At the same time, the synergistic coupling between the well-balanced charge of the zwitterionic network and the high conductivity of the PEDOT:PSS polymer facilitated efficient charge transfer. The formation of the desired molecular imprinting membrane of semi-interpenetrating hydrogel was triggered by self-polymerization of dopamine (DA) in the presence of Trp. The designed biosensor demonstrated good sensitivity, selectivity and stability in detecting the target Trp. Notably, it also exhibited exceptional anti-fouling abilities, allowing for accurate Trp detection in complex real sweat samples, yielding results comparable to commercial enzyme-linked immunoassay (ELISA).

Target-triggered cascade signal amplification in nanochannels: An ingenious strategy for ultrasensitive photoelectrochemical DNA bioanalysis.

Artificial solid-state nanochannels have aroused intense interests in biosensors and bioelectronics because of their special architectures. Herein, we pioneered an ingenious approach of target-triggered cascade signal amplification in porous anodic aluminum oxide (AAO) nanochannels for ultrasensitive photoelectrochemical (PEC) DNA bioanalysis. In the design, AAO nanochannels were modified initially with capture DNA (cDNA) and then incorporated with a photoelectrode, yielding the desired architecture of highly ordered nanoarrays on top of the signal transducer. For target DNA (tDNA) probing, exonuclease III (Exo-III) mediated target recycling (ETR) was first activated to generate plenty of output DNA (oDNA) fragments. After oDNA and the conjugate of Au-labeled probe DNA (Au-pDNA) were anchored within the nanochannels via DNA hybridization, in-situ synthesis of Ag shells on tethered Au nanoparticles was conducted. The resulting large-sized Au@Ag core-shell nanostructure within the nanochannels would cause conspicuous blocking effect to hinder the transportation of electrons accessing the photoelectrode. Since the signal inhibition was directly related to tDNA concentration, an innovative nanochannels PEC DNA assay was exploited and qualified for ultrasensitive detection. The anti-interference ability of this platform was also emphasized by the split AAO membrane for biological incubation without participation of the photoelectrode. This featured nanochannels PEC strategy with cascade amplification launched a novel detecting platform for trace levels of DNA, and it could spark more inspiration for a follow-up exploration of other smart nanochannels PEC bioassays.

Engineered Branching Peptide as Dual-Functional Antifouling and Recognition Probe: Toward a Dual-Photoelectrode Protein Biosensor with High Accuracy.

The building of practical biosensors that have anti-interference abilities against biofouling of nonspecific proteins and biooxidation of reducing agents in actual biological matrixes remains a great challenge. Herein, a robust photoelectrochemical (PEC) biosensor capable of accurate detection in human serum was pioneered through the integration of a new engineered branching peptide (EBP) into a synergetic dual-photoelectrode system. The synergetic dual-photoelectrode system involved the tandem connection of a C3N4/TiO2 photoanode and a AuPt/PANI photocathode, while the EBP as a dual-functional antifouling and recognition probe featured an inverted Y-shaped configuration with one recognition backbone and two antifouling branches. Such an EBP enables a simple procedure for electrode modification and an enhanced antifouling nature compared to a regular linear peptide (LP), as theoretically supported by the results from molecular dynamics simulations. The as-developed PEC biosensor had a higher photocurrent response and a good antioxidation property inherited from the photoanode and photocathode, respectively. Targeting the model protein biomarker of cardiac troponin I (cTnI), this biosensor achieved good performances in terms of high sensitivity, specificity, and anti-interference.

Automatically showing microbial growth kinetics with a high-performance microbial growth analyzer.

It is difficult to show microbial growth kinetics online when they grow in complex matrices. We presented a novel strategy to address this challenge by developing a high-performance microbial growth analyzer (HPMGA), which employed a unique 32-channel capacitively coupled contactless conductivity detector as a sensing element and fixed with a CellStatz software. It was capable of online showing accurate and repeatable growth curves of well-dispersed and bad-dispersed microbes, whether they grew in homogeneous simple culture broth or heterogeneous complex matrices. Moreover, it could automatically report key growth kinetics parameters. In comparison to optical density (OD), plate counting and broth microdilution (BMD) methods, we demonstrated its practicability in five scenarios: 1) the illustration of the growth, growth rate, and acceleration curves of Escherichia coli (E. coli); 2) the antimicrobial susceptibility testing (AST) of Oxacillin against Staphylococcus aureus (S. aureus); 3) the determination of Ag nanoparticle toxicity on Providencia rettgeri (P. rettgeri); 4) the characterization of milk fermentation; and 5) the enumeration of viable pathogenic Vibrio in shrimp body. Results highlighted that the HPMGA method had the advantages of universality and effectivity. This technology would significantly facilitate the routine analysis of microbial growth in many fields (biology, medicine, clinic, life, food, environment, and ecology), paving an avenue for microbiologists to achieve research goals that have been inhibited for years due to a lack of practical analytical methods.

Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva.

The construction of low-fouling biosensors for assaying biomarkers in complex biological samples remains a challenge, and the key limitation is the lack of effective anti-fouling materials. Inspired by the biomimetic process of protein phosphorylation, we herein designed a new phosphorylated peptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicity and anti-fouling capability of the peptide when compared with natural and normal peptides. Molecular simulation (MS) illustrated that, compared with the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bonds and stronger hydrogen bonds with water molecules. As a result, the PO4H2-oligopeptide was proved by MS to be able to attract the greatest number of water molecules, so as to form a compact layer of H2O to resist further adsorption of nonspecific biomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption of neutral peptide nucleic acids (PNAs) as the sensing probes, ensured the fabrication of anti-fouling electrochemical biosensors capable of detecting nucleic acids in complex saliva. The constructed anti-fouling biosensor was able to detect the nucleic acid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva, with a wide linear response range (0.01 pM-0.01 µM) and a low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylation of oligopeptides offers an effective strategy to designing ultra-hydrophilic peptides suitable for the construction of promising anti-biofouling biosensors and bioelectronics.

A Wearable Electrochemical Sensor Based on Anti-Fouling and Self-Healing Polypeptide Complex Hydrogels for Sweat Monitoring.

Although continuous monitoring of constituents in complex sweat is crucial for noninvasive physiological evaluation, biofouling on the sweat sensor surface and inadequate flexible self-healing materials restrict its applications. Herein, a fully self-healing and strong anti-biofouling polypeptide complex hydrogel (AuNPs/MoS2/Pep hydrogel) with excellent electrochemical performances was created. The anti-fouling electrochemical sweat sensor was fabricated based on the AuNPs/MoS2/Pep hydrogel to address these issues. It was found that the polypeptide hydrogel was designed to form a network structure and carried abundant hydrophilic groups, resulting in a AuNPs/MoS2/Pep hydrogel with superior anti-biofouling properties in sweat for 30 min and even long-term stability in undiluted human sweat. In addition, SEM, TEM, UV, XPS, and infrared spectrogram demonstrated that the binding force of π-π stacking force between MoS2 and naphthalene groups in the designed peptide endowed the polypeptide complex hydrogel with an excellent self-healing property. Furthermore, the polypeptide complex hydrogel preserved wearable device function of continuously monitoring uric acid (UA) and ascorbic acid (AA) in sweat in situ. This novel fabricated sweat sensor with high anti-biofouling ability, excellent self-healing property, and sensitive and selective analytical capability describes a new opportunity for health monitoring in situ.

Enzymatically Activated Autonomous-Motion DNAzyme Signal Amplification Strategy for Tumor Cell-Specific Molecular Imaging with Improved Spatial Specificity.

Strategies for achieving tumor-specific molecular imaging based on signal amplification hold great potential for evaluating the risk of tumor metastasis and progression. However, traditional amplification strategies are still constrained with limited tumor specificity because of the off-tumor signal leakage. Herein, an endogenous enzyme-activated autonomous-motion DNAzyme signal amplification strategy (E-DNAzyme) was rationally designed for tumor-specific molecular imaging with improved spatial specificity. The sensing function of E-DNAzyme can be specifically activated by the overexpressed apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm of tumor cells instead of normal cells, ensuring the tumor cell-specific molecular imaging with improved spatial specificity. Of note, benefiting from the target analogue-triggered autonomous motion of the DNAzyme signal amplification strategy, the detection limit can be decreased by approx. ∼7.8 times. Moreover, the discrimination ratio of tumor/normal cells of the proposed E-DNAzyme was ∼3.44-fold higher than the traditional amplification strategy, indicating the prospect of this universal design for tumor-specific molecular imaging.