Shengyuan Deng

The tumor microenvironment (TME) is spatially and temporally heterogeneous, limiting the specificity of single-biomarker strategies for resolving complex tumor states. The sequence programmability and predictable base pairing of DNA allow multiple biological inputs to be recognized, logically processed, and translated into defined analytical outputs. Here, we review recent advances in DNA logic-gated biosensors and associated nanodevices for multicomponent TME profiling, spanning nucleic acids, proteins, extracellular vesicles, and physicochemical cues. Particular attention is directed to how molecular recognition, Boolean computation, signal amplification, and transduction collectively govern analytical specificity, signal-to-noise ratio, reaction kinetics, and operational reliability in complex biological matrices. We further compare chemical stabilization, smart delivery, and spatial confinement strategies, together with applications in tumor phenotyping, immune-response monitoring, molecular imaging, and conditional therapeutic activation. Emerging directions include continuous and wearable monitoring, spatially organized molecular circuits, and advanced DNA molecular computing. Translation, however, will require improved nuclease resistance, delivery efficiency, threshold robustness, fabrication reproducibility, clinical-matrix validation, and system-level integration. By converting multicomponent TME signals into programmable molecular decisions, DNA logic-gated biosensing may support more reliable tumor characterization, precision diagnosis, and context-dependent therapy.

Microwave-free optical readout of nitrogen-vacancy (NV–) centers based on magnetic-field-dependent photodynamics and magnetic modulation provides a route for sensing without microwave excitation, yet its use in calibrated trace paramagnetic-ion analysis remains underdeveloped. In this work, we combine DOTA-functionalized silica-coated fluorescent nanodiamond (FND@SiO2-DOTA) probes, low-frequency magnetic modulation, UNet-ConvLSTM-based signal-pixel identification, and pixelwise lock-in-amplitude analysis to detect weak paramagnetic effects without microwave excitation or frequency sweeping. Using Gd3+ as a model paramagnetic ion, the lock-in readout achieves a detection limit of 51.8 pM, which is lower than that obtained from optically detected magnetic resonance contrast measurements under the same probe system and comparable to T1 relaxometry. By distinguishing modulated FND pixels from the optical background and extracting a lock-in signal, this approach provides a streamlined workflow for Gd3+-referenced trace paramagnetic-ion sensing.

Excessive fluoride (F ⁻ ) exposure poses a threat to environmental and biological systems, necessitating rapid and reliable recognition.

Electrochemiluminescence (ECL) is intrinsically a surface‐state‐sensitive strategy, yet its seamless synergy with soft biomembranes remains sparsely explored. Herein, a biolipid‐bound, membrane‐interactive scaffold is built upon an ECL‐emissive artificial nanochannel and smoothly blended into supported phospholipid bilayers containing cholesterol and diversified natural or synthetic lipids. Such bilayer‐bridged assemblies preserve efficient emission while permitting dynamic membrane remodeling. The resulting biointerface enables label‐free profiling of cytomembrane‐active species, including divalent cations, amphiphilic pharmaceuticals, and pore‐forming peptides, through real‐time isotherm and kinetic analysis. By further integrating phospholipid‐pendant recognition motifs, femtomolar detection of Alzheimer's disease biomarkers (β‐amyloid polypeptide and tau protein) is achieved. Moreover, vesicle‐mediated membrane merging embeds ECL emitters into living‐cell plasmalemma, affording surface‐confined single‐cell visualization using endogenous oxygen as the coreactant. Collectively, this biointerface‐compatible ECL paradigm enables multiplexed monitoring of molecular, membranous, and cellular processes via membrane‐structural modulation.

Electrochemiluminescence (ECL) is traditionally realized with conformationally rigid luminophores, where suppression of intra-molecular motion is regarded as a prerequisite for efficient emission. Here, we report a fundamentally inverse ECL paradigm ena-bled by lanthanide-bridged double-decker porphyrin molecular rotors, in which electrically stimulated intramolecular rotation amplifies ECL output. Using La3+/Ce4+ bis(tetra(pyridyl)porphyrin) complexes as prototypical systems, we demonstrate that anod-ic electrooxidation induces elongation of La−N coordination bonds and softening of the sandwich framework, thereby accelerating circumrotation of the porphyrinic decks around the lanthanide stator and concomitantly strengthening ECL emission ("spin-enhanced ECL"). A combination of electrochemical spectroscopy, electrochemical circular dichroism, viscosity- and diffusion-resolved measurements, and density functional theory calculations establishes a quantitative correlation among rotational dynam-ics, electronic structure reorganization, and ECL intensity. Furthermore, four classes of rotation regulators: protic acids, penetrat-ing cations, supramolecular hosts, and bivalent binders, are identified as rotary accelerators or decelerators, enabling bidirectional and competitive modulation of ECL through a unified rotational coordinate. This work introduces intramolecular rotation as an electrodynamically addressable variable in ECL and provides a mechanistic foundation for rotationally responsive ECL lumino-phores, offering a new strategy for motion-coupled light-emitting systems and analytical signal transduction.

Early diagnosis of acute myocardial infarction (AMI) urgently demands point-of-care testing (POCT) technology for cardiac troponin I (cTnI) that integrates hypersensitivity and cost-effectiveness. Conventional POCT methods either fail to detect the signal of low-abundance cTnI (1.5~2.0 pg/mL) in the early stage due to insufficient sensitivity, or are difficult to popularize at the grassroots level owing to the high cost of high-sensitivity detection schemes; while quantum sensing technology, despite its potential for single-molecule signal capture, confronts the core bottleneck of poor adaptability to biological scenarios. To tackle the challenge above, this study constructed a multi-sensitivity quantum sensing detection system (MQSenS) integrated with the quantum-classical hybrid (QCH) algorithm for early, precise cTnI detection. It constructs a stable bio-quantum interface by conjugating carboxylated fluorescent nanodiamonds (FND−COOH) with cTnI-specific antibodies. Through a customized near-field resonant antenna (NFRA) hardware platform, it achieves stable manipulation of negative-charged nitrogen-vacancy (NV−) center spin states at 2.87 GHz. To address the efficiency and fidelity challenges in quantum frame data processing, a quantum frame-selection sieve (QFSS) framework was proposed, which integrated Grover’s algorithm with generalized Bell entangled state measurement to efficiently screen bright/dark frames and determine quantum state attribution, thereby generating high-fidelity stack masks for model training. Furthermore, an artificial intelligence (AI)-enhanced quantum signal lock-in purifier (Q-LIP-AI) based on the Feature Fusion Unet-ConvLSTM-Attention (FFUnet-ConvLSTM-Attention) network was developed, adopting a dual-AI parallel architecture to deeply mine weak quantum signals and break through the sensitivity limitations of traditional lock-in analysis. Performance validation showed MQSenS’s limit of detection for cTnI is as low as 21.4 fM - 1168-fold more sensitive than conventional colloidal Au POCT and outperforming clinically prevalent chemiluminescence immunoassays. It achieves 100% detection sensitivity for sample concentration range from 10−11 to 10−9 M and 91.1% in the ultra-trace range (10−14~10−12 M). A single test takes only 6 min, with cost comparable to conventional fluorescence-based lateral flow assays, breaking the inherent trade-off between high-sensitivity detection, low cost, and rapid testing. This study not only provides a feasible technical solution for AMI early diagnosis in primary medical institutions but also proposes a "simulator-first, algorithm-empowered, scenario-adapted" clinical translation paradigm for quantum technology, laying a solid foundation for the implementation of quantum sensing in precision medicine.

Mitochondria-lysosome interactions are critical for maintaining cellular homeostasis. Although genetically encoded protein based optogenetic technique is developed to regulate such interactions, it still suffers from shortcomings including complicated operation and potential interference to organelle functions. Here, we present a fast, simple, biocompatible and programmable platform via activable DNA regulators to achieve spatiotemporal regulation of mitochondria-lysosome interactions in living cells. In our system, two locked DNA regulators, OK-MLIR and DK-MLIR, that can be respectively activated with UV light (One Key) as well as UV light and endogenous glutathione (Dual Keys), are modularly designed for modulating mitochondria-lysosome contacts. We show that these DNA regulators can be used for facilitating mitochondrial fission and autophagy. Moreover, the DK-MLIR enables selective and efficient manipulation of target cell migration and proliferation with highly temporal and spatial controllability. This programmable and modular design principle provides a platform for organelle interaction study, cellular regulation and precision therapy.

Chronic diseases (CDs) and their associated hepatic and renal dysfunctions pose grim global health challenges, severely compromising quality of life while increasing morbidity and mortality rates. In China, a big bottleneck in effective CD management lies in the lack of affordable and efficient point-of-care testing (POCT) methods at the primary care level. To address this, we developed a Prussian blue (PB) nanozyme-based dry dipstick reflectometric platform for probing key metabolic markers associated with hyperglycemia, hyperuricemia, hypercholesterolemia, and hyperlipidemia. Gram-scale synthesis of PB nanozymes was successfully secured using ethylene glycol as a crowding agent and antifouling additive. The nanozyme showed superb catalytic performance, with an activity approximately 67-fold higher than that of horseradish peroxidase (HRP), while reducing the per-test cost by up to 55.9-fold compared to the HRP-based ensemble. A considerably cost-effective quadruple sensing strip was shaped up by coimmobilizing PB nanozymes with substrate-specific oxidases, chromogen, and proton donors. This enabled the simultaneous detection of glucose, uric acid, cholesterol, and triglycerides using only 50 μL of the sample. Integrated with a smartphone-mounted detector, the slides succeeded in multiplexed assay of serum-simulated samples within 6 min, demonstrating superb repeatability (overall coefficients of variation <5%). The detection limits were 0.52 mM for glucose, 0.025 mM for uric acid, 0.18 mM for cholesterol, and 0.425 mM for triglycerides, with corresponding linear ranges of 2-30, 0.1-1.0, 1-10, and 0.5-7 mM, respectively. This on-paper approach holds strong strength for expanding to other CD indicators (e.g., aspartate, alanine aminotransferase, urea, creatinine), fostering biohybrid POCT solutions for broader clinical applications.