Biological Imaging Applications Research Articles

Disorder-Enhanced Charge-Transfer-Mediated Room-Temperature Phosphorescence in Polymer Media.

Room-temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder-enabled freedoms of microscopic motions can be beneficial for charge-transfer-mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the "classic" pyrene-aniline exciplex as an example, we demonstrate the mutual enhancement of red/near-infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene-doped crystal formed with the same aniline structure exhibits only charge-transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi-emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge-transfer complexes.

Disorder‐Enhanced Charge‐Transfer‐Mediated Room‐Temperature Phosphorescence in Polymer Media

AbstractRoom‐temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder‐enabled freedoms of microscopic motions can be beneficial for charge‐transfer‐mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the “classic” pyrene‐aniline exciplex as an example, we demonstrate the mutual enhancement of red/near‐infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene‐doped crystal formed with the same aniline structure exhibits only charge‐transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi‐emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge‐transfer complexes.

Methylene blue based near-infrared fluorogenic probe for lighting up esterase activity and its application in biological imaging

In this work, a light-up near-infrared (NIR) fluorescence probe based on methylene blue was developed for the determination of esterase. Probe MB-Ace emits a significant NIR fluorescence at 691 nm while incubated with esterase, which facilitates us to accurately detect the activity of esterase in vitro and vivo. MB-Ace showed high sensitivity (with a detection limit of 5.2 ng/mL) and selectivity to esterase under the interference of various biomolecules. The results of biological imaging experiments showed that MB-Ace had cell membrane permeability and could be used to monitor esterase activity in Hep G2 cells. At the same time, MB-Ace also showed excellent imaging ability for esterase activity in a mice model. The above results reflect the application value of MB-Ace in the early diagnosis of liver cancer and image-guided tumor resection.

Simultaneous chiral polarization and edge enhancement imaging enabled by a single geometric-phase-based element.

In this Letter, we propose a multifunctional imaging system enabled by a single geometric-phase-based liquid crystal (LC) element, which integrates chiral polarization and edge enhancement imaging. The element is located at the frequency domain plane in a 4F imaging system, and the phase profile of the element consists of a fork grating in the x direction and a grating in the y direction, which provide edge enhancement and chiral polarization imaging capabilities. Benefiting from the tunable property of the LC, the system can be switched from a polarization and edge imaging mode to the normal conventional imaging mode which is capable of conveniently acquiring the needed image information. Experiments demonstrate that the system can easily achieve multifunctional and switchable imaging, which agrees well with our design, and our LC element can work in the broadband spectrum because of the geometric phase modulation. The multifunctional strategy used here can effectively avoid the need to increase the size of the original microscopic system and the need for additional mechanical rotation of components. We believe that the proposed system with the additional advantages of electric control and tunability can find applications in biological imaging, medical detection, and optical computing.

Implementing the edge enhancement with vortex filter in both linear and nonlinear optics

The edge enhancement technique, as an effective method to represent the boundary of objects, plays an important role in image processing. Among them, the vortex filtering, which is based on the radial Hilbert transformation, has been paid great attention due to its ability to achieve isotropic and anisotropic edge enhancement. Recent years have witnessed a growing interest in the nonlinear vortex filter to skillfully realize the visualization of the object edge under invisible light irradiation. In this paper, we start from reviewing the achievements have been made with the vortex filtering technique in linear optics, and then discussed the recent processes of the scalar and vector vortex filter in nonlinear optics. We hope that the nonlinear optical vortex filter can motivate some promising applications in biological edge imaging with visible light-sensitive specimens.

Heterobimetallic lanthanide tetrahedral cages: Synthesis, design and application for potential multimodal imaging contrast agent

The construction and functionalization of lanthanide-organic cages have been a research hotspot in coordination chemistry. Benefiting from the unique luminescent and magnetic properties of lanthanide ions, the potential applications of lanthanide-organic cages in biological imaging applications are promising, but only a few corresponding explorations have been reported. Herein, we introduced a series of lanthanide tetrahedral cages, (EunGd4–nL4) (sol)8 (n = 0, 1, 2, 3 and 4, where L = (4,4′,4″-tris(4,4,4-trifluoro-1,3-dioxobutyl)-triphenylamine, and sol = dimethyl sulfoxide and methanol), with potential applications in biological imaging. Given the good luminescent and magnetic properties of Eu3+ and Gd3+ ions, Eu4L4 and Gd4L4 complexes show a high luminescence quantum yield of 29% in DMSO and large longitudinal relaxivity (r1) of 11.4 (mmol/L)−1/s at 0.5 T in water containing 1 vol% DMSO, respectively. The heterobimetallic Eu–Gd complexes achieve a dual imaging mode by combining luminescent and magnetic centers in one cage. When the Gd:Eu ratio increases from 1:3 to 3:1, the r1 values increases from 5.33 to 8.64 (mmol/L)−1/s, higher than that of commercial contrast agent Gd-DOTA (3.23 (mmol/L)−1/s). Owing to their low toxicity and good cell imaging ability toward ECA 109 cells, the self-assembled Eu–Gd heterobimetallic tetrahedral cages could be potential candidates for the multimodal imaging contrast agent.

Incorporation of Eu3+ in ZnGa2O4:Ni2+ for improved NIR persistent luminescence located in second transparency window

AbstractIt is well known that near‐infrared (NIR) persistent phosphors have rather low absorption coefficients of biological tissues for NIR light. However, recent research shows that the phosphors emitting NIR lights in second NIR (NIR‐II, 1000–1350 nm) and third (NIR‐III, 1500–1800 nm) biological window have advantages over that in NIR‐I (650–900 nm). Although ZnGa2O4:Ni2+ outputs NIR emission and afterglow locatedin NIR‐II, the weak signal significant limits its application. In this work, persistent luminescent phosphors of ZnGa2O4:xNi2+, yEu3+ (x = 0–0.013, y = 0.01–0.06) (termed as ZEGN) were synthesized via a traditional high‐temperature solid‐state reaction, which feature a broad emission band in the NIR‐II window. The phosphors exhibit a broad NIR emission at about 1300 nm after ultraviolet (UV) or orange–red lights excitation, arising from the 3T2(3F) → 3A2(3F) transition of Ni2+. However, incorporation of Eu3+ ions, the NIR emission intensity significantly increases with the increase of Ni2+ ion concentration, reaching the maximum by 18 times at x = 0.005. Removing the light source, the sample still outputs intense NIR afterglow and red afterglow that can last over 500 s. It is noteworthy that the red afterglow of Eu3+ shows a dramatically decrease but the NIR afterglow increases with increasing the Ni2+ ion concentration, because of energy transfer. Under the excitation of 282‐nm UV light, the ZGEN sample exhibits a good thermal stability. The phosphor offers a promising application in biological imaging due to broadband NIR‐II light and afterglow.

Dual-Functional Tunable Metasurface for Meta-Axicon with a Variable Depth of Focus and Continuous-Zoom Metalens.

Optical metasurfaces have been widely investigated for their versatile ability to manipulate wavefront and miniaturize traditional optical components into ultrathin planar devices. The integration of metasurfaces with multifunctionality and tunability has fundamentally transformed optics with unprecedented control over light propagation and manipulation. This study introduces a pioneering framework for the development of tunable metasurfaces with multifunctionality, and an example of a tunable metasurface of dual functionalities is proposed and numerically verified as one of the tunable meta-axicon for generating Bessel beams with a variable depth of focus (DOF) and a continuous-zoom metalens. Specifically, this design achieves dual-functional phase modulation by helicity-multiplexing from the combination of the geometric phase as well as the propagation phase and realizes tunability for both functionalities through rotational actuation between double metasurface layers. As a result, dual functionalities with continuous tunability of the proposed TiO2 metasurface are enabled independently for the left and right circularly polarized (LCP and RCP) incidences at 532 nm. Specifically, LCP light triggers the metasurface to function as a tunable axicon, generating non-diffracting Bessel beams with variable numerical apertures (NA) and DOFs. Conversely, the RCP incidence induces it to operate as a continuous-zoom metalens and generates variable spherical wavefront focusing on diverse focal lengths. This study not only initially implements the design of tunable meta-axicon, but also achieves the integration of such a tunable meta-axicon and continuous-zoom metalens within a single metasurface configuration. The proposed device could find potential applications in biological imaging, microscopic measurement, laser fabrication, optical manipulation, multi-plane imaging, depth estimation, optical data storage, etc.

Development of a colorimetric and turn-on fluorescent probe with large Stokes shift for H2S detection and its multiple applications in environmental, food analysis and biological imaging

A new colorimetric and turn-on fluorescent probe NPC-H2S with a large Stokes shift (227 nm) was designed and synthesized for the detection of hydrogen sulfide (H2S) in environmental, food analysis and biological imaging. NPC-H2S was strategically constructed by employing a new corrole derivate (NPC–OH) as the fluorophore and a benzenesulfonyl group (DNBS) as the identification moiety and fluorescence quencher. NPC-H2S displays high selectivity and sensitivity for H2S over various analytes with fluorescent “off-on” ultra-fast recognition (10 s), a low limit of detection (61 nM), and a naked-eye colorimetric change from green to yellow. Importantly, NPC-H2S has been successfully applied for the detection of H2S in the actual water samples and monitoring the spoilage of food samples such as chicken, beef, pork, fish, cracked egg and full egg, as well as for fluorescent bioimaging of H2S in living cells and zebrafish.

A dual-responsive fluorescent probe based on cyanine and naphthalimide units for detecting HClO and H2S in living cells

Hypochlorous acid (HClO) and hydrogen sulfide (H2S) play very important roles in both physiological and pathological processes, however, the methods for simultaneously detecting HClO and H2S were rarely reported. Here, a dual–responsive fluorescent probe (CyNa-N3) based on cyanine and naphthalimide dyes was synthesized and investigated. The fluorescence probe showed better sensitivity, high selectivity response to HClO and H2S by red emission and green emission bands, and the limits of detection were 0.17 µM and 0.15 µM respectively. MS (Mass Spectrum) and 1H NMR (Nuclear Magnetic Resonance) confirmed the sensing mechanism of CyNa-N3 detected HClO and H2S, the calculation of density functional theory (DFT) further explained the internal mechanism of spectral change of CyNa-N3. Moreover, CyNa-N3 was successfully applied to image HClO and H2S in living cells, which is beneficial for more efficient application in biological imaging.

Current and Future of "Turn-On" Based Small-Molecule Copper Probes for Cuproptosis.

Increasing evidence shows that abnormal copper (Cu) metabolism is highly related to many diseases, such as Alzheimer's disease, Wilson's disease, hematological malignancies and Menkes disease. Very recently, cuproptosis, a Cu-dependent, programmed cell death was firstly described by Tsvetkov et al. in 2022. Their findings may provide a new perspective for the treatment of related diseases. However, the concrete mechanisms of these diseases, especially cuproptosis, remain completely unclear, the reason of which may be a lack of reliable tools to conduct highly selective, sensitive and high-resolution imaging of Cu in complex life systems. So far, numerous small-molecular fluorescent probes have been designed and utilized to explore the Cu signal pathway. Among them, fluorescence turn-on probes greatly enhance the resolution and accuracy of imaging and may be a promising tool for research of investigation into cuproptosis. This review summarizes the probes developed in the past decade which have the potential to study cuproptosis, focusing on the design strategies, luminescence mechanism and biological-imaging applications. Besides, we put forward some ideas concerning the design of next-generation probes for cuproptosis, aiming to tackle the main problems in this new field. Furthermore, the prospect of cuproptosis in the treatment of corresponding diseases is also highlighted.

Comprehensive Analysis of Dual Core Photonic Crystal Fibers for Optimizing Optical Properties Towards Highly Coherent Supercontinuum Generation

A systematic study implementing numerical analysis has been presented in this work in order to design a hexagonal lattice dual core photonic crystal fiber (DC-PCF) which will be simple to fabricate but possesses very good values of optical properties for supercontinuum generation (SCG). By utilizing a full vectoral finite element method with perfectly matched boundary conditions, important propagation properties are numerically evaluated and tuned to desired value through the optimization of structural parameters. Finally, it is found that the optimized PCF structure exhibits very low confinement loss, high birefringence, large effective mode area while maintaining negative chromatic dispersion of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$-$</tex-math></inline-formula> 8.3138 ps/km.nm pumping at 1060 nm wavelength. The fiber when excited by a hyperbolic secant pulse having a full-width at half-maximum (FWHM) of 50 fs and a relatively low energy of 4 nJ generates a SC spectrum spanning 600 nm to 1600 nm. The effect of altering the pump power and other parameters on the generated spectra is also explored. Furthermore, the input noise effects on generated SCs have been analyzed through the inclusion of different types of noise. It is found that the generated SC demonstrates excellent coherence property over the entire band extended from visible to the near-IR region and thus it may find applications in lasing, biological imaging, and telecommunication.

An AIE-based ratiometric fluorescent probe for reversible detection of bisulfite and hydrogen peroxide and its application in food samples and biological imaging

Reversible detection of bisulfite (HSO3-) and hydrogen peroxide (H2O2) is highly desirable in biology and food safety owing to their redox pair function in biological systems and their utilization in food industry. In this work, a ratiometric fluorescent probe (TPA-Y) with aggregation-induced emission (AIE) properties based on triphenylamine fluorophore was designed and synthesized for reversibly monitoring of HSO3-/H2O2. Reaction of HSO3- with TPA-Y can result in ratiometric fluorescence changes (I444/I629), and the emission spectrum blue shift reaches 185 nm, which can effectively avoid spectral overlap. Meanwhile, the solution color changed obviously from orange to colorless, enabling naked eye detection of HSO3-. TPA-Y was capable of quantitatively detect HSO3- in sugar and wine samples with the recovery rates ranging from 94.52 to 102.18%. In addition, TPA-Y is suitable to prepare paper strips and anti-counterfeiting ink for HSO3- detection. In addition, the original TPA-Y can be released after the addition product (TPA-Y-HSO3-) is oxidized by H2O2, and the HSO3-/H2O2 redox cycle can repeat for at least six times. The probe TPA-Y can be applied to fluorescence imaging of reversible and dynamic interconversion between HSO3- and H2O2 in living MCF-7 cells.

Boron Ketoimine Fluorophores with Unique Optical Properties: Multicolor Tuning, Efficient Dual‐State Emission, and Reversible Acid‐Base Response

AbstractOrganic luminophores with high emission efficiency in solution as well as solid‐state have received increasing attention due to their promising applications in biosensors, biological imaging, and optoelectronic devices. Herein, four triphenylamine (TPA)‐substituted boron ketoimine molecules (TPA‐BKI a‐d) are designed and synthesized by combining a donor‐acceptor (D‐A) electronic system and highly twisted block. The asymmetry of molecular and the planarity of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) sides in the excited state endow TPA‐BKI a‐d with rigidified conformations, allowing bright emission in dilute solution. Additionally, their highly twisted structures avoid close contact between molecules and detrimental exciton interactions, leading to efficient emission in the solid state. Meanwhile, the emission colors are modulated by the incorporation of different substituents through the amino‐yne click reaction. Furthermore, because of the protonation and deprotonation of the amino substituents, TPA‐BKI‐d exhibits reversible alterations of optical properties in both solution and solid states.

Ratiometric fluorescent probe with signals from two near-infrared channels for esterase activity and its application in biological imaging

Esterase serves as a crucial biomarker for the diagnosis of tumors due to its overexpression in cancer cells. Ratiometric fluorescent probe has the advantage of having two distinct emission wavelengths, which allows for the elimination of the effects of light intensity and optical path length by using the fluorescence intensity ratio between the two emission wavelengths. In this work, a novel near-infrared (NIR) fluorescent probe P1 for ratiometric monitor esterase activity was developed. Compared with ordinary ratiometric probes, both emission wavelengths of this probe are in the NIR region, which can effectively eliminate various fluctuations and blurriness in image contrast and achieve precise quantitative analysis. P1 itself shows a fluorescence emission at 717 nm. After incubated with esterase, a new emission peak at 822 nm emerged due to esterase's catalysis, and the fluorescence intensity at 717 nm steadily decreased, which achieved the highly sensitive detection of esterase with a detection limit calculated as 0.25 mU/mL. What’s more, P1 showed high selectivity for esterase and was successfully applied for biological imaging in living cells and in vivo.

The H2S detection based on the combined smartphone technology and cellulose composite film and its application in biological imaging

In this study, flavonoids were used as fluorophores and dinitrobenzenesulfonyl groups as recognition groups. A novel fluorescent probe, LBS-XY, with high sensitivity and selectivity for H2S was prepared by nucleophilic addition and nucleophilic substitution reactions. The LBS-XY enables rapid detection of H2S within 150 s with a limit of detection (LOD) as low as 0.041 μM. With the interference of other ions (or molecules), only H2S was able to cause the probe to fluoresce in a green color visible to the naked eye. The probe can be used to realize the detection of H2S in real water samples by smartphone technology, and the fluorescent composite film prepared from the probe also achieved satisfactory results. In addition, the probe was successfully used to image hydrogen sulfide in A549 cells. The results demonstrate the potential of probe LBS-XY for applications in multiple fields.

Electroosmotic flow of cobalt-ferrite nanoparticles in water and ethylene glycol through a ciliary annulus: A biomedical application.

Unique magnetic characteristics of cobalt-ferrite nanoparticles make them suitable for biological imaging and therapeutic applications. Understanding their activity in nanofluids via the ciliary annulus could lead to better contrast agents for magnetic resonance imaging and improved cancer therapy and other medical therapies. This article provides a comprehensive analysis of the theoretical conclusions regarding the transport of a nanofluid by electroosmosis across a ciliary annulus. The nanofluid consists of cobalt-ferrite nanoparticles (CoFe2O4), water (H2O), and ethylene glycol (C2H6O2). As part of the investigation into constructing a physical model, mathematical analysis is performed based on the conservation of mass, momentum, and energy. Dimension-free analysis and mathematical constraints are utilized to learn more about the system. By generating differential equations and including suitable boundary conditions, one can obtain exact solutions, which can then be visually inspected. Recent studies have demonstrated an inverse relationship between flow velocity and cilia length, zeta potential, and Helmholtz-Smoluchowski velocity. The streamlines show that the growth of the trapping boluses is affected by several factors, including the nanoparticles' volume fraction, the cilia's length, the amplitude ratio, the eccentricity, and the zeta potential. These results not only shed light on how nanofluids move, but they also have potential applications in microfluidics, heat transfer, and biomedical engineering.

Boosting the Brightness of Raman Tags Using Cyanostar Macrocycles.

Raman probes have received growing attention for their potential use in super-multiplex biological imaging and flow cytometry applications that cannot be achieved using fluorescent probes. However, obtaining strong Raman scattering signals from small Raman probes has posed a challenge that holds back their practical implementation. Here, we present new types of Raman-active nanoparticles (Rdots) that incorporate ionophore macrocycles, known as cyanostars, to act as ion-driven and structure-directing spacers to address this problem. These macrocycle-enhanced Rdots (MERdots) exhibit sharper and higher electronic absorption peaks than Rdots. When combined with resonant broadband time-domain Raman spectroscopy, these MERdots show a ∼3-fold increase in Raman intensity compared to conventional Rdots under the same particle concentration. Additionally, the detection limit on the concentration of MERdots is improved by a factor of 2.5 compared to that of Rdots and a factor of 430 compared to that of Raman dye molecules in solution. The compact size of MERdots (26 nm in diameter) and their increased Raman signal intensity, along with the broadband capabilities of time-domain resonant Raman spectroscopy, make them promising candidates for a wide range of biological applications.

Multifunctional gold nanorod composite for NIR imaging and photodynamic therapy treatment of tumor

The preparation of an effective functional nanomaterial that combines near-infrared imaging and photodynamic therapy functions remains a highly challenging task. The unique tunable optical properties of gold nanorods in the near-infrared region compensate for the limitations of traditional fluorescent dyes and other metal nanoparticles in biological imaging applications. Gold nanorods play a crucial role in biological tissue imaging, early cancer diagnosis and therapy. In this paper, we got gold nanorods in different aspect ratio by adjusting the content of AgNO3 in the growth solution. Subsequently, we developed a novel multi-functional delivery system (5-ALA-loaded GNRs@SiO2@PHIS) using GNRs as cores. The nanocomposite was loaded with a photosensitizer called 5-Aminolevulinic acid (ALA) and conjugated with a pH-sensitive polymer called poly-histidine (PHIS). The PHIS can induce pH-triggered drug release and facilitate endo/lysosome escape, thereby enhancing drug efficacy. The current study on in vitro experiments indicated that the multifunctional gold nanorod composite exhibit strong light scattering in the near-infrared region and effectively induced cancer cell through photodynamic therapy treatment. Overall, this study presents an innovative strategy for the development of versatile photodynamic therapy for cancer theranostics.

BODIPY-based fluorescent probe for cysteine detection and its applications in food analysis, test strips and biological imaging.

Cysteine, as one of semi-essential amino acids, which is absorbed from protein-rich foods and acts considerable role in various physiological processes. Here, we designed and synthesized a BODIPY-based turn-on fluorescent probe BDP-S for detecting Cys. The probe displayed short reaction time (10min), distinct color response (from blue to pink), large signal noise ratio (3150-fold), high selectivity and sensitivity (LOD=11.2nM) toward Cys. Moreover, BDP-S could not only be used for quantitative determination of Cys in food samples, but also be conveniently deposited on the test strips for qualitative detection of Cys. Notably, BDP-S was successfully used for imaging Cys in living cells and in vivo. Consequently, this work provided a hopefully powerful tool for detecting Cys in food samples and complex biological systems.