Meso‐Functionalization of Silk Fibroin by Upconversion Fluorescence and Near Infrared In Vivo Biosensing

In biomedical applications, it is very desirable to monitor the in vivo state of implanted devices, i.e., tracking the location, the state, and the interaction between the implanted devices and cell tissues. To achieve this goal, a generic strategy of soft materials meso‐functionalization is presented. This is to acquire silk fibroin (SF) materials with added functions, i.e., in vivo bioimaging/sensing. The functionalization is by 3D materials assembly of functional components, lanthanide(Ln)‐doped upconversion nanoparticles (UCNPs) on the mesoscopic scale to acquire upconversion fluorescent emission. To implement the meso‐functionalization, the surfaces of UCNPs are modified by the hydroxyl groups (? OH) from SiO₂ or polyethylene glycol coating layers, which can interact with the carbonyl groups (C?O) in SF scaffolds. The functionalized silk scaffolds are further implanted subcutaneously into mice, which allows the silk scaffolds to have fluorescent in vivo bioimaging and other biomedical functions. This material functionalization strategy may lead to the rational design of biomaterials in a more generic way.     

Phosphorescent Polymeric Thermometers for In Vitro and In Vivo Temperature Sensing with Minimized Background Interference

Temperature plays a crucial role in many biological processes. Accurate temperature determination is important for diagnosis and treatment of diseases. Autofluorescence is an unavoidable interference in luminescent bioimaging. Hence, a large amount of research works has been devoted to reducing background autofluorescence and improving signal‐to‐noise ratio (SNR) in biodetection. Herein, a dual‐emissive phosphorescent polymeric thermometer has been developed by incorporating two long‐lived phosphorescent iridium(III) complexes into an acrylamide‐based thermosensitive polymer. Upon increasing temperature, this polymer undergoes coil‐globule transition, which leads to a decrease in polarity of the microenvironment surrounding the iridium(III) complexes and hence brings about emission enhancement of both complexes. Owing to their different sensitivity to surrounding environment, the emission intensity ratio of the two complexes is correlated to the temperature. Thus, the polymer has been used for temperature determination in vitro and in vivo via ratiometric luminescence imaging. More importantly, by using the long‐lived phosphorescence of the polymer, temperature mapping in zebrafish has been demonstrated successfully with minimized autofluorescence interference and improved SNR via time‐resolved luminescence imaging. To the best of our knowledge, this is the first example to use photoluminescent thermometer for in vivo temperature sensing.     

Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T2‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb³⁺/Tm³⁺ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb³⁺ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF₄:Yb³⁺/Tm³⁺ UCNPs. PEG‐UCNPs‐5 (98% Yb³⁺) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T₂‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T₂‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.     

基于上转换荧光的三维立体显示

简要介绍了三维立体显示的现状,重点阐述了基于上转换荧光的三维立体显示的原理和特点,分析了现存在的技术难题,指出了今后的发展方向.     

Removing the Obstacle of Dye‐Sensitized Upconversion Luminescence in Aqueous Phase to Achieve High‐Contrast Deep Imaging In Vivo

Although upconversion nanoparticles (UCNPs) have drawn increasing attention for their unique photophysical characteristics, they suffer from a bottleneck of low luminescence efficiency due to the poor absorption coefficient of Ln³⁺. Dye sensitization has provided thousands‐fold enhancement of upconversion luminescence (UCL) in organic solvents because of the remarkably improved light absorption ability, but the sensitization of UCL in aqueous phase is only less than 20 folds by far, with unknown restrictive factors. Herein, the aggregation‐caused quenching (ACQ) of dyes is revealed as the most important reason limiting dye sensitization in aqueous phase, and the problem is circumvented through delicately modulating the physical properties of dyes and their assembly manner with UCNPs. By further alleviating energy back transfer (EBT) from Ln³⁺ to dyes, more than 600‐fold enhancement of UCL is achieved in aqueous phase. The as‐obtained dyes modified UCNPs show good biocompatibility and high signal contrast when applied for deep in vivo imaging.     

Visible and NIR Upconverting Er3+–Yb3+ Luminescent Nanorattles and Other Hybrid PMO‐Inorganic Structures for In Vivo Nanothermometry

Lanthanide‐doped luminescent nanoparticles are an appealing system for nanothermometry with biomedical applications due to their sensitivity, reliability, and minimal invasive thermal sensing properties. Here, four unique hybrid organic–inorganic materials prepared by combining β‐NaGdF₄ and PMOs (periodic mesoporous organosilica) or mSiO₂ (mesoporous silica) are proposed. PMO/mSiO₂ materials are excellent candidates for biological/biomedical applications as they show high biocompatibility with the human body. On the other hand, the β‐NaGdF₄ matrix is an excellent host for doping lanthanide ions, even at very low concentrations with yet very efficient luminescence properties. A new type of Er³⁺–Yb³⁺ upconversion luminescence nanothermometers operating both in the visible and near infrared regime is proposed. Both spectral ranges permit promising thermometry performance even in aqueous environment. It is additionally confirmed that these hybrid materials are non‐toxic to cells, which makes them very promising candidates for real biomedical thermometry applications. In several of these materials, the presence of additional voids leaves space for future theranostic or combined thermometry and drug delivery applications in the hybrid nanostructures.     

Dual Phase‐Controlled Synthesis of Uniform Lanthanide‐Doped NaGdF4 Upconversion Nanocrystals Via an OA/Ionic Liquid Two‐Phase System for In Vivo Dual‐Modality Imaging

A novel OA/ionic liquid two‐phase system combining the merits of thermal decomposition method, the IL‐based strategy, and the two‐phase approach is introduced to synthesize high‐quality lanthanide‐doped NaGdF₄ upconversion nanocrystals with different crystal‐phases in OA‐phase and IL‐phase through a one‐step controllable reaction. Oil‐dispersible cubic‐phase NaGdF₄:Yb, Er (Ho, Tm) nanocrystals with ultra‐small size (～5 nm) and monodispersity are obtained in the OA phase of the two‐phase system via an IL‐based reaction. More importantly, water‐soluble hexagonal‐phase NaGdF₄:Yb, Er nanocrystals are obtained in the same system simply by adopting an extremely facile method to complete the dual phase‐transition (crystal‐phase transition and OA‐phase to IL‐phase transition) simultaneously. The synthesized lanthanide‐doped NaGdF₄ upconversion nanocrystals are effective for dual‐mode UCL imaging and CT imaging in vivo.     

In Vivo Implantable Strain Sensor for Real-Time and Precise Pathophysiological Monitoring of Contractile Living Organs

Early diagnosis based on precise monitoring of the vital organs in real-time can provide the opportunity for subsequent curative treatments and medical decisions. Here, it is reported that the instantaneous monitoring of physiological responses in contractile living organs such as the heart, lung, and urinary bladder using a vertical graphene strain sensor (VGS), which possesses remarkable sensitivity and stability. The electrical resistance of VGS (i.e., sensitivity) corresponding to the minute contractile motion of living organs is monitored, which displacement in organs is less than a few mm in scale. For pathological diagnosis, it is compared normal and damage rodent models, including models of myocardial infarction, pulmonary fibrosis, and spinal cord injury, highlighting the capability of the VGS sensor to discern symptoms and guide medical decisions based on the lesions. The results suggest that the VGS could be useful in implantable biocompatible applications and may be a promising component of in vivo diagnostic platforms.     

3D Micromolding of Arrayed Waveguide Gratings on Upconversion Luminescent Layers for Flexible Transparent Displays without Mirrors,Electrodes, and Electric Circuits

A new technique for the fabrication of arrayed waveguide gratings on upconversion luminescent layers for flexible transparent displays is reported. Ho³⁺‐ and Yb³⁺‐codoped NaYF₄ nanoparticles are synthesized by hydrothermal techniques. Transparent films consisting of two transparent polymers on the NaYF₄ nanoparticle films exhibit mechanical flexibility and high transparence in visible region. Patterned NaYF₄ nanoparticle films are fabricated by calcination‐free micromolding in capillaries. Arrayed waveguide gratings consisting of the two transparent polymers are formed on the patterned NaYF₄ nanoparticle films by micromolding in capillaries. Green and red luminescence is observed from the upconversion luminescent layers of the NaYF₄ nanoparticle films in the arrayed waveguide gratings under excitation at 980 nm laser light. Arrayed waveguide gratings on the upconversion luminescent layers are fabricated with Er³⁺‐doped NaYF₄ nanoparticles which can convert two photons at 850 and 1500 nm into single photon at 550 nm. These results demonstrate that flexible transparent displays can be fabricated by constructing arrayed waveguide gratings on upconversion luminescent layers, which can operate in nonprojection mode without mirrors, transparent electrodes, and electric circuits.     

Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS Biosensing

Multimodal imaging provides complimentary information that is advantageous in studying both cellular and molecular mechanisms in vivo, which has tremendous potential in pre‐clinical research and clinical translational imaging. It is desirable to design probes for multimodal imaging that can be administered minimally but provides multifaceted information. Herein, we demonstrate the complementary dual functional ability of a nanoconstruct for molecular imaging in both photoacoustic (PA) and surface‐enhanced Raman scattering (SERS) biosensing simultaneously in tandem. To realize this, a group of NIR active organic molecules are designed and synthesized that possess both SERS and PA activity. Nanoconstructs realized by anchoring such molecules onto gold nanoparticles are demonstrated for targeting cancer biomarkers in vivo while providing complimentary information about biodistribution and targeting efficiency. In future, such nanoconstructs could play a major role in identifying surgical margins and also for disease monitoring in translational medicine.     

Nanoparticle‐Based Fluoroionophore for Analysis of Potassium Ion Dynamics in 3D Tissue Models and In Vivo

The imaging of real‐time fluxes of K⁺ ions in live cell with high dynamic range (5–150 × 10^?3m ) is of paramount importance for neuroscience and physiology of the gastrointestinal tract, kidney, and other tissues. In particular, the research on high‐performance deep‐red fluorescent nanoparticle‐based biosensors is highly anticipated. It is found that boron‐dipyrromethene (BODIPY)‐based K⁺‐sensitive fluoroionophore FI3 encapsulated in cationic polymer RL100 nanoparticles displays unusually strong efficiency in staining of broad spectrum of cell models, such as primary neurons and intestinal organoids. Using comparison of brightness, photostability, and fluorescence lifetime imaging microscopy, it is confirmed that FI3 nanoparticles display distinctively superior intracellular staining compared to the free dye. FI3 nanoparticles in real‐time live cell imaging are evaluated and it is found highly useful for monitoring intra‐ and extracellular K⁺ dynamics in cultured neurons. Proof‐of‐concept in vivo brain imaging confirms applicability of the biosensor for visualization of epileptic seizures. Collectively, these data make fluoroionophore FI3 a versatile cross‐platform fluorescent biosensor, broadly compatible with diverse experimental models, and crown‐ether‐based polymer nanoparticles can provide a new venue for the design of efficient fluorescent probes.     

Porous Silicon‐Based Optical Microsensors for Volatile Organic Analytes: Effect of Surface Chemistry on Stability and Specificity

Sensing of the volatile organic compounds (VOCs) isopropyl alcohol (IPA) and heptane in air using sub‐millimeter porous silicon‐based sensor elements is demonstrated in the concentration range 50–800 ppm. The sensor elements are prepared as one‐dimensional photonic crystals (rugate filters) by programmed electrochemical etch of p⁺⁺ silicon, and analyte sensing is achieved by measurement of the wavelength shift of the photonic resonance. The sensors are studied as a function of surface chemistry: ozone oxidation, thermal oxidation, hydrosilylation (1‐dodecene), electrochemical methylation, reaction with dicholorodimethylsilane and thermal carbonization with acetylene. The thermally oxidized and the dichlorodimethylsilane‐modified materials show the greatest stability under atmospheric conditions. Optical microsensors are prepared by attachment of the porous Si layer to the distal end of optical fibers. The acetylated porous Si microsensor displays a greater response to heptane than to IPA, whereas the other chemical modifications display a greater response to IPA than to heptane. The thermal oxide sensor displays a strong response to water vapor, while the acetylated material shows a relatively weak response. The results suggest that a combination of optical fiber sensors with different surface chemistries can be used to classify VOC analytes. Application of the miniature sensors to the detection of VOC breakthrough in a full‐scale activated carbon respirator cartridge simulator is demonstrated.     

Flexible Battery-Free Wireless Sensor Array Based on Functional Gradient-Structured Wood for Pressure and Temperature Monitoring

Approximately 4.5% to 7.0% of hospitalized patients suffer from pressure ulcers. Mitigating risks for pressure ulcers through sensors remains a challenge and a high requirement. A simple, low-cost, battery-free, multi-parameter passive wireless flexible sensor (MPWFS) for all-around pressure and temperature monitoring to prevent pressure ulcers is developed. The pressure sensing unit is fabricated with functional gradient-structured balsa wood and has high sensitivity of 0.34 kPa⁻¹ with a wide detection range of 0–20 kPa. The temperature sensing unit, which is 0.4 mm × 0.2 mm, is embedded in the surface of the pressure sensing unit, enabling temperature monitoring with a resolution of 0.1 °C. The flexible Radio Frequency energy-harvesting unit, data acquisition, and processing, as well as Bluetooth-Low-Energy wireless transmission, are integrated within a 20 mm × 20 mm unit. It acquires continuous temperature and pressure data without a battery at any position more than 1 m away from the power transmitter. Moreover, the combination of the sensor array design with a mobile terminal provides the MPWFS's various benefits, including tracking changes in the supine posture, warning about pressure ulcers, and monitoring falls out of bed. This study presents a new method for long-term bedridden patient care.     

Rational Design of Capacitive Pressure Sensors Based on Pyramidal Microstructures for Specialized Monitoring of Biosignals

There is an increasing demand for specialized pressure sensors in various applications. Previously, capacitive pressure sensors have been shown to have wide versatility in use, with a high degree of potential tuning possible through manipulating the geometry or material selection of the dielectric layer. However, in order to make sensors that are tunable and predictable, the design and fabrication method first needs to be developed. Presented here is an improved fabrication method to achieve tunable, consistent, and reproducible pressure sensors by using a pyramid microstructured dielectric layer along with a lamination layer. The as‐produced sensor performance is able to match predicted trends. Further, a simple model based on this system is developed and its efficacy is experimentally confirmed. Then, the model to predict a wide range of material and microstructure geometric properties prior to device fabrication is used to provide trends on sensor performance. Finally, it is demonstrated that the new method can be used to targetedly design a pressure sensor for a specific application—in vitro pulse sensing.     

A Combinatorial Approach for Colorimetric Differentiation of Organic Solvents Based on Conjugated Polymer‐Embedded Electrospun Fibers

A combinatorial approach for the colorimetric differentiation of organic solvents is developed. A polydiacetylene (PDA)‐embedded electrospun fiber mat, prepared with aminobutyric acid‐derived diacetylene monomer PCDA‐ABA 1, displays colorimetric stability when exposed to common organic solvents. In contrast, a fiber mat prepared with the aniline‐derived diacetylene PCDA‐AN 2 undergoes a solvent‐sensitive color transition. Arrays of PDA‐embedded microfibers are constructed by electrospinning poly(ethylene oxide) solutions containing various ratios of two diacetylene monomers. Unique color patterns are developed when the conjugated polymer‐embedded electrospun fiber arrays are exposed to common organic solvents in a manner which enables direct colorimetric differentiation of the tested solvents.     

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

Printed Capacitive Sensors Based on Ionic Liquid/Metal-Organic Framework Composites for Volatile Organic Compounds Detection

In this paper, the potential of 2D printing technologies to create thin film gas sensors from ionic liquid (IL)/metal–organic framework (MOF) composites is evaluated. To accomplish this, the MOF is synthesized solvothermally, and impregnated with the IL. The structure and basic properties of the IL/MOF composites are characterized using thermal, spectroscopic, and X-ray diffraction techniques, and the resultant sensing capacity of the bulk material is evaluated by impedance spectroscopy. The IL/MOF systems are then integrated into a 2D printed silver capacitive circuit by spray and tested on a custom-made gas flow apparatus. Exposure of the IL/MOF based sensors to water, acetone, and ethanol induces a repetitive variation of the capacitance (from 0.05 to 7 pF) that is dependent on the nature of the gas. IL/MOF based sensors can detect changes in concentrations in the range of 10k–100k ppm in less than a second. The conclusions of this work are the first steps towards the development of 2D printed sensors based on IL/MOF materials. Such materials offer countless possibilities to tailor the porosity, chemistry, selectivity, and electrical response to make the sensor suitable to detect the desired analyte.     

Biocompatible Nanoparticles Based on Diketo‐Pyrrolo‐Pyrrole (DPP) with Aggregation‐Induced Red/NIR Emission for In Vivo Two‐Photon Fluorescence Imaging

Compared with traditional one‐photon fluorescence imaging, two‐photon fluorescence imaging techniques have shown advantages such as increased penetration depth, lower tissue autofluorescence, and reduced photo­damage, and therefore are particularly useful for imaging tissues and animals. In this work, the design and synthesis of two novel DPP ‐based compounds with large two‐photon absorption (2PA) cross‐sections (σ ≥ 8100 GM) and aggregation‐induced emission (AIE) properties are reported. The new compounds are red/NIR emissive and show large Stokes shifts (Δλ ≥ 3571 cm^?1). 1,2‐Distearoyl‐sn‐glycero‐3‐phosphoethanol amine‐N‐[maleimide(polyethylene glycol)‐2000 (DSPE‐PEG‐Mal) is used as the encapsulation matrix to encapsulate DPP‐2 , followed by surface functionalization with cell penetrating peptide (CPP) to yield DPP‐2‐CPP nanoparticles with high brightness, good water dispersibility, and excellent biocompatibility. DPP‐2 nanoparticles have been used for cell imaging and two‐photon imaging with clear visualization of blood vasculature inside mouse ear skin with a depth up to 80 μm.