ZnS/C/MoS2 Nanocomposite Derived from Metal–Organic Framework for High‐Performance Photo‐Electrochemical Immunosensing of Carcinoembryonic Antigen

A hexafluorophosphate ionic liquid is used as a functional monomer to prepare a metal–organic framework (Zn‐MOF). Zn‐MOF is used as a template for MoS₂ nanosheets synthesis and further carbonized to yield light‐responsive ZnS/C/MoS₂ nanocomposites. Zn‐MOF, carbonized‐Zn‐MOF, and ZnS/C/MoS₂ nanocomposites are characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, X‐ray diffraction pattern, scanning electron microscopy (SEM), element mapping, Raman spectroscopy, X‐ray photoelectron spectroscopy, fluorescence, and nitrogen‐adsorption analysis. Carcinoembryonic antigen (CEA) is selected as a model to construct an immunosensing platform to evaluate the photo‐electrochemical (PEC) performances of ZnS/C/MoS₂ nanocomposites. A sandwich‐type PEC immunosensor is fabricated by immobilizing CEA antibody (Ab₁) onto the ZnS/C/MoS₂/GCE surface, subsequently binding CEA and the alkaline phosphatase‐gold nanoparticle labeled CEA antibody (ALP‐Au‐Ab₂). The catalytic conversion of vitamin C magnesium phosphate produces ascorbic acid (AA). Upon being illuminated, AA can react with photogenerated holes from ZnS/C/MoS₂ nanocomposites to generate a photocurrent for quantitative assay. Under optimized experimental conditions, the PEC immunosensor exhibits excellent analytical characteristics with a linear range from 2.0 pg mL^?1 to 10.0 ng mL^?1 and a detection limit of 1.30 pg mL^?1 (S/N = 3). The outstanding practicability of this PEC immunosensor is demonstrated by accurate assaying of CEA in clinical serum samples.     

Aminolated and Thiolated PEG‐Covered Gold Nanoparticles with High Stability and Antiaggregation for Lateral Flow Detection of Bisphenol A

The few lateral flow assays (LFAs) established for detecting the endocrine disrupting chemical bisphenol A (BPA) have employed citrate‐stabilized gold nanoparticles (GNPs), which have inevitable limitations and instability issues. To address these limitations, a more stable and more sensitive biosensor is developed by designing strategies for modifying the surfaces of GNPs with polyethylene glycol and then testing their effectiveness and sensitivity toward BPA in an LFA. Without the application of any enhancement strategy, this modified BPA LFA can achieve a naked‐eye limit of detection (LOD) of 0.8 ng mL^?1, which is 12.5 times better than the LOD of regular BPA LFAs, and a quantitative LOD of 0.472 ng mL^?1. This modified LFA has the potential to be applied to the detection of various antigens.     

A Chiral‐Nanoassemblies‐Enabled Strategy for Simultaneously Profiling Surface Glycoprotein and MicroRNA in Living Cells

Assemblies of nanomaterials for biological applications in living cells have attracted much attention. Herein, graphene oxide (GO)–gold nanoparticle (Au NP) assemblies are driven by a splint DNA strand, which is designed with two regions at both ends that are complementary with the DNA sequence anchored on the surface of the GO and the Au NPs. In the presence of microRNA (miR)‐21 and epithelial cell‐adhesion molecule (EpCAM), the hybridization of miR‐21 with a molecular probe leads to the separation of 6‐fluorescein‐phosphoramidite‐modified Au NPs from GO, resulting in a decrease in the Raman signal, while EpCAM recognition reduces circular dichroism (CD) signals. The CD signals reverse from negative in original assemblies into positive when reacted with cells, which correlates with two enantiomer geometries. The EpCAM detection has a good linear range of 8.47–74.78 pg mL^?1 and a limit of detection (LOD) of 3.63 pg mL^?1, whereas miR‐21 detection displays an outstanding linear range of 0.07–13.68 amol ng^?1_RNA and LOD of 0.03 amol ng^?1_RNA. All the results are in good agreement with those of the Raman and confocal bioimaging. The strategy opens up an avenue to allow the highly accurate and reliable diagnosis (dual targets) of clinic diseases.     

Chiral Shell Core–Satellite Nanostructures for Ultrasensitive Detection of Mycotoxin

Herein, the design of a DNA‐based chiral biosensor is described utilizing the self‐assembly of shell core–gold (Au) satellite nanostructures for the detection of mycotoxin, ochratoxin A (OTA). The assembly of core–satellite nanostructures based on OTA‐aptamer binding exhibits a strong chiral signal with an intense circular dichroism (CD) peak. The integrity of the assembly of core–satellite nanostructures is limited to some extent in the presence of different levels of OTA. Correspondingly, the chiral intensity of assembly is weakened with increasing OTA concentrations, allowing quantitative determination of the target. The developed chiral sensor shows an excellent linear relationship between the CD signal and concentrations of OTA in the range of 0.1–5 pg mL^?1 with a limit of detection as low as 0.037 pg mL^?1. The effectiveness of the biosensor in a sample of red wine is verified and a good recovery rate is obtained. These results suggest that the strategy has great potential for practical application.     

High‐Throughput,Protein‐Targeted Biomolecular Detection Using Frequency‐Domain Faraday Rotation Spectroscopy

A clinically relevant magneto‐optical technique (fd‐FRS, frequency‐domain Faraday rotation spectroscopy) for characterizing proteins using antibody‐functionalized magnetic nanoparticles (MNPs) is demonstrated. This technique distinguishes between the Faraday rotation of the solvent, iron oxide core, and functionalization layers of polyethylene glycol polymers (spacer) and model antibody–antigen complexes (anti‐BSA/BSA, bovine serum albumin). A detection sensitivity of ≈10 pg mL^?1 and broad detection range of 10 pg mL^?1 ? c_BSA ? 100 µ g mL^?1 are observed. Combining this technique with predictive analyte binding models quantifies (within an order of magnitude) the number of active binding sites on functionalized MNPs. Comparative enzyme‐linked immunosorbent assay (ELISA) studies are conducted, reproducing the manufacturer advertised BSA ELISA detection limits from 1 ng mL^?1 ? c_BSA ? 500 ng mL^?1. In addition to the increased sensitivity, broader detection range, and similar specificity, fd‐FRS can be conducted in less than ≈30 min, compared to ≈4 h with ELISA. Thus, fd‐FRS is shown to be a sensitive optical technique with potential to become an efficient diagnostic in the chemical and biomolecular sciences.     

Sandwiched Electrochemiluminescent Peptide Biosensor for the Detection of Prognostic Indicator in Early‐Stage Cancer Based on Hollow,Magnetic, and Self‐Enhanced Nanosheets

Currently, peptide‐based protein‐recognition has been recognized as an effective and promising approach for protein assays. However, sandwiched peptide‐based biosensor with high sensitivity and low background has not been proposed before. Herein, a sandwiched electrochemiluminescence (ECL) peptide‐based biosensor is constructed for Cyclin A₂ (CA2), a prognostic indicator in early stage of multiple cancers, based on nanosheets with hollow, magnetic, and ECL self‐enhanced properties. First, hollow and magnetic manganese oxide nanocrystals (H‐Mn₃O₄) are synthesized using triblock copolymeric micelles with core–shell–corona architecture as templates. Then, polyethyleneimine (PEI) and the composite of platinum nanoparticles and tris (4,4′‐dicarboxylicacid‐2,2′‐bipyridyl) ruthenium (II) (PtNPs–Ru) are immobilized on H‐Mn₃O₄ to form H‐Mn₃O₄–PEI–PtNPs–Ru nanocomposite, in which PEI as coreactant can effectively enhance the luminous efficiency and PtNPs as nanochannels can greatly accelerate the electron transfer. Finally, due to the coordination between Eu³⁺ and carboxyl, the obtained H‐Mn₃O₄–PEI–PtNPs–Ru aggregates locally to form sheet‐like nanostructures ((H‐Mn₃O₄–PEI–PtNPs–Ru)_n–Eu³⁺), by which the luminous efficiency is further increased. Based on the nanosheets and two designed peptides, a sandwiched ECL biosensor, using palladium nanocages synthesized through galvanic replacement reaction as substrate, is proposed for CA2 with a linear range from 0.001 to 100 ng mL^?1 and a detection limit of 0.3 pg mL^?1.     

Hyperboloid‐Drum Microdisk Laser Biosensors for Ultrasensitive Detection of Human IgG

Whispering gallery mode (WGM) microresonators have been used as optical sensors in fundamental research and practical applications. The majority of WGM sensors are passive resonators that require complex systems, thereby limiting their practicality. Active resonators enable the remote excitation and collection of WGM‐modulated fluorescence spectra, without requiring complex systems, and can be used as alternatives to passive microresonators. This paper demonstrates an active microresonator, which is a microdisk laser in a hyperboloid‐drum (HD) shape. The HD microdisk lasers are a combination of a rhodamine B‐doped photoresist and a silica microdisk. These HD microdisk lasers can be utilized for the detection of label‐free biomolecules. The biomolecule concentration can be as low as 1 ag mL^?1, whereas the theoretical detection limit of the biosensor for human IgG in phosphate buffer saline is 9 ag mL^?1 (0.06 a_M). Additionally, the biosensors are able to detect biomolecules in an artificial serum, with a theoretical detection limit of 9 ag mL^?1 (0.06 a_M). These results are approximately four orders of magnitude more sensitive than those for the typical active WGM biosensors. The proposed HD microdisk laser biosensors show enormous detection potential for biomarkers in protein secretions or body fluids.     

Metal‐Ion‐Modified Black Phosphorus with Enhanced Stability and Transistor Performance

Black phosphorus (BP), a burgeoning elemental 2D semiconductor, has aroused increasing scientific and technological interest, especially as a channel material in field‐effect transistors (FETs). However, the intrinsic instability of BP causes practical concern and the transistor performance must also be improved. Here, the use of metal‐ion modification to enhance both the stability and transistor performance of BP sheets is described. Ag⁺ spontaneously adsorbed on the BP surface via cation–π interactions passivates the lone‐pair electrons of P thereby rendering BP more stable in air. Consequently, the Ag⁺‐modified BP FET shows greatly enhanced hole mobility from 796 to 1666 cm² V^?1 s^?1 and ON/OFF ratio from 5.9 × 10⁴ to 2.6 × 10⁶. The mechanisms pertaining to the enhanced stability and transistor performance are discussed and the strategy can be extended to other metal ions such as Fe³⁺, Mg²⁺, and Hg²⁺. Such stable and high‐performance BP transistors are crucial to electronic and optoelectronic devices. The stability and semiconducting properties of BP sheets can be enhanced tremendously by this novel strategy.     

Oxidase‐Like Fe‐N‐C Single‐Atom Nanozymes for the Detection of Acetylcholinesterase Activity

Single‐atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe‐N‐C SACs can mimic oxidase by activating O₂ into reactive oxygen species, O₂^?? radicals. Taking advantages of this property, single‐atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe‐N‐C SACs as oxidase‐like nanozymes is explored. Besides, the Fe‐N‐C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes‐based biosensor is further used for monitoring the amounts of organophosphorus compounds.     

Sortase A‐Generated Highly Potent Anti‐CD20‐MMAE Conjugates for Efficient Elimination of B‐Lineage Lymphomas

Antibody–drug conjugate (ADC) targeting antigens expressed on the surface of tumor cells are an effective approach for delivering drugs into the cells via antigen‐mediated endocytosis. One of the well‐known tumor antigens, the CD20 of B‐lymphocyte, has long been suggested to be noninternalizing epitope, and is thus not considered a desirable target for ADCs. Here, sortase A (srtA)‐mediated transpeptidation is used to specifically conjugate triple glycine‐modified monomethyl auristatin E (MMAE), a highly toxic antimitotic agent, to anti‐CD20 ofatumumab (OFA) equipped with a short C‐terminal LPETG (5 amino acids) tag at heavy chain (HL), which generates ADCs that show extremely strong potency in killing CD20 positive cancer cells. One of the srtA‐generated ADCs with a cleavable dipeptide linker (valine‐citrulline, vc), OFA‐HL‐vcMMAE, shows IC50 values ranging from 5 pg mL^?1 to 4.1 ng mL^?1 against CD20+ lymphoma cells. Confocal laser scanning microscopy confirms that OFA‐HL‐vcMMAE internalization by Ramos cells is significantly improved compared to OFA alone, consistent with the high antitumor activity of the new ADC. OFA‐HL‐vcMMAE, at 5 mg kg^?1 dose, is able to eliminate tumors with mean volume ≈400 mm³ while no obvious drug‐related toxicity is observed. The results show that srtA‐generated OFA‐MMAE conjugate system provides a viable strategy for targeting CD20+ B lineage lymphomas.     

Plasmonic Metasurfaces Based on Nanopin‐Cavity Resonator for Quantitative Colorimetric Ricin Sensing

In view of the toxic potential of a bioweapon threat, rapid visual recognition and sensing of ricin has been of considerable interest while remaining a challenging task up to date. In this study, a gold nanopin‐based colorimetric sensor is developed realizing a multicolor variation for ricin qualitative recognition and analysis. It is revealed that such plasmonic metasurfaces based on nanopin‐cavity resonator exhibit reflective color appearance, due to the excitation of standing‐wave resonances of narrow bandwidth in visible region. This clear color variation is a consequence of the reflective color mixing defined by different resonant wavelengths. In addition, the colored metasurfaces appear sharp color difference in a narrow refractive index range, which makes them especially well‐suited for sensing applications. Therefore, this antibody‐functionalized nanopin‐cavity biosensor features high sensitivity and fast response, allowing for visual quantitative ricin detection within the range of 10–120 ng mL^?1 (0.15 × 10^?9–1.8 × 10^?9 m ), a limit of detection of 10 ng mL^?1, and the typical measurement time of less than 10 min. The on‐chip integration of such nanopin metasurfaces to portable colorimetric microfluidic device may be envisaged for the quantitative studies of a variety of biochemical molecules.     

Therapeutic Window of Ligand‐Free Silver Nanoparticles in Agar‐Embedded and Colloidal State: In Vitro Bactericidal Effects and Cytotoxicity

The inhibition of bacterial growth through effective non‐toxic antimicrobial substances is of great importance for the prevention and therapy of implant infections in various medical disciplines. For the evaluation of a therapeutic window of silver nanoparticles (AgNPs), their bactericidal properties were tested in agar composites and colloids on four medical relevant bacteria. Therefore, we produced AgNPs using high‐power nanosecond laser ablation in water showing a log‐normal particle diameter distribution centered at 17 nm. Bacteria were incubated with AgNP concentrations ranging from 5 to 70 µg · mL^?1 and the growth rate was recorded. Additionally, cytotoxic effects of AgNPs on human gingival fibroblasts were examined. The experiments demonstrated that laser‐synthesized AgNPs resulted in a significant bacterial growth inhibition of more than 80% at the indicated concentrations in a solid agar model (Pseudomonas aeruginosa 10 µg · mL^?1, Streptococcus salivarius 10 µg · mL^?1, Escherichia coli 20 µg · mL^?1, Staphylococcus aureus 70 µg · mL^?1). In a planktonic bacteria model, the growth of the tested bacteria was significantly delayed by the addition of AgNPs at a concentration of 35 µg · mL^?1. The cytotoxic assays showed limited adverse effects on human fibroblasts at concentrations of less than 20 µg · mL^?1. The present study illustrates the strong antibacterial effects of ligand‐free, laser‐generated AgNPs that exhibit moderate cytotoxic effects, resulting in a therapeutically applicable concentration of AgNPs for medical purposes between 10 and 20 µg · mL^?1.     

Highly Efficient Photocatalytic Hydrogen Evolution by ReS2 via a Two‐Electron Catalytic Reaction

Highly efficient photocatalytic hydrogen evolution (PHE) is highly desirable for addressing the global energy crisis and environmental problems. Although much attention has been given to electron–hole separation, ridding photocatalysts of poor efficiency remains challenging. Here, a two‐electron catalytic reaction is developed by utilizing the distinct trion behavior of ReS₂ and the efficient reduction of two H⁺ (2H⁺ + 2e^? → H₂) is realized. Due to the monolayer‐like structure of the catalyst, the free electrons in ReS₂ can be captured by the tightly bound excitons to form trions consisting of two electrons and one hole. These trions can migrate to the surface and participate in the two‐electron reaction at the abundant active sites. As expected, such a two‐electron catalytic reaction endows ReS₂ with a PHE rate of 13 mmol g^?1 h^?1 under visible light irradiation. Meanwhile, this reaction allows the typically poor PHE efficiency of pure transition metal dichalcogenides to be overcome. The proposed two‐electron catalytic reaction provides a new approach to the design of photocatalysts for PHE.     

Rapid and Digital Detection of Inflammatory Biomarkers Enabled by a Novel Portable Nanoplasmonic Imager

New point‐of‐care diagnostic devices are urgently needed for rapid and accurate diagnosis, particularly in the management of life‐threatening infections and sepsis, where immediate treatment is key. Sepsis is a critical condition caused by systemic response to infection, with chances of survival drastically decreasing every hour. A novel portable biosensor based on nanoparticle‐enhanced digital plasmonic imaging is reported for rapid and sensitive detection of two sepsis‐related inflammatory biomarkers, procalcitonin (PCT) and C‐reactive protein (CRP) directly from blood serum. The device achieves outstanding limit of detection of 21.3 pg mL^?1 for PCT and 36 pg mL^?1 for CRP, and dynamic range of at least three orders of magnitude. The portable device is deployed at Vall d'Hebron University Hospital in Spain and tested with a wide range of patient samples with sepsis, noninfectious systemic inflammatory response syndrome (SIRS), and healthy subjects. The results are validated against ultimate clinical diagnosis and currently used immunoassays, and show that the device provides accurate and robust performance equivalent to gold‐standard laboratory tests. Importantly, the plasmonic imager can enable identification of PCT levels typical of sepsis and SIRS patients in less than 15 min. The compact and low‐cost device is a promising solution for assisting rapid and accurate on‐site sepsis diagnosis.     

Electrochemical Biosensor Composed of Silver Ion‐Mediated dsDNA on Au‐Encapsulated Bi2Se3 Nanoparticles for the Detection of H2O2 Released from Breast Cancer Cells

A newly developed electrochemical biosensor composed of a topological insulator (TI) and metallic DNA (mDNA) is fabricated. The bismuth selenide nanoparticle (Bi₂Se₃ NP) is synthesized and sandwiched between the gold electrode and another Au‐deposited thin layer (Bi₂Se₃@Au). Then, eight‐silver‐ion mediated double‐stranded DNA (mDNA) is immobilized onto the substrate (Bi₂Se₃@Au‐mDNA) for the further detection of hydrogen peroxide. The Bi₂Se₃ NP acts as the electrochemical‐signal booster, while unprecedentedly its encapsulation by the Au thin layer keeps the TI surface states protected, improves its electrochemical‐signal stability and provides an excellent platform for the subsequent covalent immobilization of the mDNA through Au–thiol interaction. Electrochemical results show that the fabricated biosensor represents much higher Ag⁺ redox current (≈10 times) than those electrodes prepared without Bi₂Se₃@Au. The characterization of the Bi₂Se₃@Au‐mDNA film is confirmed by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetry. The proposed biosensor shows a dynamic range of 00.10 × 10^?6m to 27.30 × 10^?6m , very low detection limit (10 × 10^?9m ), unique current response (1.6 s), sound H₂O₂ recovery in serum, and substantial capability to classify two breast cancer subtypes (MCF‐7 and MDA‐MB‐231) based on their difference in the H₂O₂ generation, offering potential applications in the biomedicine and pharmacology fields.     

Investigating the Hybrid‐Structure‐Effect of CeO2‐Encapsulated Au Nanostructures on the Transfer Coupling of Nitrobenzene

Due to the obvious distinctions in structure, core–shell nanostructures (CSNs) and yolk–shell nanostructures (YSNs) exhibit different catalytic behavior for specific organic reactions. In this work, two unique autoredox routes are developed to the fabrication of CeO₂‐encapsulated Au nanocatalysts. Route A is the synthesis of well‐defined CSNs by a one‐step redox reaction. The process involves an interesting phenomenon in which Ce³⁺ can act as a weak acid to inhibit the hydrolysis of Ce⁴⁺ under the condition of OH^? shortage. Route B is the fabrication of monodispersed YSNs by a two‐step redox reaction with amorphous Co₃O₄ as an in situ template. Furthermore, the transfer coupling of nitrobenzene is chosen as a probe reaction to investigate their catalytic difference. The CSNs can gradually achieve the conversion of nitrobenzene into azoxybenzene, while the YSNs can rapidly convert nitrobenzene into azobenzene. The different catalytic results are mainly attributed to their structural distinctions.     

Well‐Balanced Ambipolar Conjugated Polymers Featuring Mild Glass Transition Temperatures Toward High‐Performance Flexible Field‐Effect Transistors

Conjugated polymers, which can be fabricated by simple processing techniques and possess excellent electrical performance, are key to the fabrication of flexible polymer field‐effect transistors (PFETs) and integrated circuits. Herein, two ambipolar conjugated polymers based on (3E,7E)‐3,7‐bis(2‐oxo‐1H‐pyrrolo[2,3‐b]pyridin‐3(2H)‐ylidene)benzo[1,2‐b:4,5‐b′]difuran‐2,6(3H,7H)‐dione and dithienylbenzothiadiazole units, namely PNBDOPV‐DTBT and PNBDOPV‐DTF2BT , are developed. Both copolymers possess almost planar conjugated backbone conformations and suitable highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels (?5.64/?4.38 eV for PNBDOPV‐DTBT and ?5.79/?4.48 eV for PNBDOPV‐DTF2BT ). Note that PNBDOPV‐DTBT has a glass transition temperature (140 °C) lower than the deformation temperature of polyethylene terephthalate (PET), meaning well‐ordered molecular packing can be obtained on PET substrate before its deformation in mild thermal annealing process. Flexible PFETs based on PNBDOPV‐DTBT fabricated on PET substrates exhibit high and well‐balanced hole/electron mobilities of 4.68/4.72 cm² V^?1 s^?1 under ambient conditions. After the further modification of Au source/drain electrodes with 1‐octanethiol self‐assembled monolayers, impressively high and well‐balanced hole/electron mobilities up to 5.97/7.07 cm² V^?1 s^?1 are achieved in the flexible PFETs. Meanwhile, flexible complementary‐like inverters based on PNBDOPV‐DTBT on PET substrate also afford a much high gain of 148. The device performances of both the PFETs and inverters are among the highest values for ambipolar conjugated polymers reported to date.     

High‐Concentration Solvent Exfoliation of Graphene

A method is demonstrated to prepare graphene dispersions at high concentrations, up to 1.2 mg mL^?1, with yields of up to 4 wt% monolayers. This process relies on low‐power sonication for long times, up to 460 h. Transmission electron microscopy shows the sonication to reduce the flake size, with flake dimensions scaling as t^?1/2. However, the mean flake length remains above 1 µm for all sonication times studied. Raman spectroscopy shows defects are introduced by the sonication process. However, detailed analysis suggests that predominately edge, rather than basal‐plane, defects are introduced. These dispersions are used to prepare high‐quality free‐standing graphene films. The dispersions can be heavily diluted by water without sedimentation or aggregation. This method facilitates graphene processing for a range of applications.     

DNA‐Driven Two‐Layer Core–Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells

It is a significant challenge to achieve controllable self‐assembly of superstructures for biological applications in living cells. Here, a two‐layer core–satellite assembly is driven by a Y‐DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two‐layer core–satellite nanostructure (C₃₀S₅S₁₀ NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface‐enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g‐factor of 0.16 × 10^?2. The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011–20.94 amol ng_RNA^?1 and a limit of detection (LOD) of 0.0051 amol ng_RNA^?1, while Raman signal with the range of 0.052–34.98 amol ng_RNA^?1 and an LOD of 2.81 × 10^?2 amol ng_RNA^?1. This innovative dual‐signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.