Biological Imaging Applications Research Articles

A metasurface-on-fiber light-sheet generator for biological imaging

Light sheet has been widely used for bioimaging. However, it is a big challenge to build a miniature light-sheet imaging system due to geometric constraints of bulky refractive and diffractive elements. Metasurface-based devices composed of subwavelength unit cells, with compact size and the ability to effectively manipulate optical fields, have been considered as potential planar analogs of conventional components to realize various functionalities. Integrating metasurfaces onto an optical fiber facet is sparking new ideas and emerging applications. Here, we propose a metasurface-on-fiber light-sheet generator, which can convert a fiber mode to a thin light sheet. By adopting a multi-core fiber and a dielectric metasurface on its facet, a light sheet with a thickness of 2 μm and a length of 83.0 μm is obtained. The generator can greatly simplify the illumination of light sheet imaging systems and be flexibly used for advanced biological imaging applications.

A novel Zn2+-coordination fluorescence probe for sensing HPPD inhibitors and its application in environmental media and biological imaging

Mesotrione, topramezone, tembotrione, and sulcotrione are four types of 4-hydroxyphenylpyruvate dioxidase (HPPD) inhibitor herbicides that are extensively employed in agricultural practices, but their usage also leads to environmental pollution and poses risks to human health. A probe (E)−1-((2-(pyridin-2-yl) hydrazineylidene) methyl) naphthalen-2-ol (CHMN) based on chelation enhancement (CHEF) effect synthesized. CHMN was first chelated with Zn2+ to form a probe system with green, which can be further used to detect mesotrione, topramezone, tembotrione and sulcotrione in complicated environment. CHMN-Zn2+ detection of four pesticides was accurate, with an excellent linear relationship between 0 and 100 μM. The detection limits were LODmesotrione = 7.79 μM, LODtopramezone = 1.91 μM, LODtembotrione = 1.38 μM and LODsulcotrione = 2.43 μM. The detection time is 1 min, and it is successfully applied in real water sample and bioimaging. This work can provide a novel method for studying the migration and behavior of environmental pollutants.

Nanoscale Metal-Organic Frameworks and Nanoscale Coordination Polymers: From Synthesis to Cancer Therapy and Biomedical Imaging.

Recently, there has been significant interest in nanoscale metal-organic frameworks (NMOFs) characterized by ordered crystal structures and nanoscale coordination polymers (NCPs) featuring amorphous structures. These structures arise from the coordination interactions between inorganic metal ions or clusters and organic ligands. Their advantages, such as the ability to tailor composition and structure, efficiently encapsulate diverse therapeutic or imaging agents within porous frameworks, inherent biodegradability, and surface functionalization capability, position them as promising carriers in the biomedical fields. This review provides an overview of the synthesis and surface modification strategies employed for NMOFs and NCPs, along with their applications in cancer treatment and biological imaging. Finally, future directions and challenges associated with the utilization of NMOFs and NCPs in cancer treatment and diagnosis are also discussed.

Cholesterols Induced Distinctive Entry of the Graphene Nanosheet into the Cell Membrane.

Graphene nanosheets are highly valued in the biomedical field due to their potential applications in drug delivery, biological imaging, and biosensors. Their biological effects on mammalian cells may be influenced by cholesterols, which are crucial components in cell membranes that take part in many vital processes. Therefore, it is particularly important to investigate the effect of cholesterols on the transport mechanism of graphene nanosheets in the cell membrane as well as the final stable configuration of graphene, which may have an impact on cytotoxicity. In this paper, the molecular details of a graphene nanosheet interacting with a 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) membrane with cholesterols were studied using molecular dynamics simulations. Results showed that the structure of the graphene nanosheet transits from the cut-in state in a pure DPPC membrane to being sandwiched between two DPPC leaflets when cholesterols reach a certain concentration. The underlying mechanism showed that cholesterols are preferentially adsorbed on the graphene nanosheet, which causes a larger disturbance to the nearby DPPC tails and thus guides the graphene nanosheet into the core of lipid bilayers to form a sandwiched structure. Our results are helpful for understanding the fundamental interaction mechanism between the graphene nanosheet and cell membrane and to explore the potential applications of the graphene nanosheet in biomedical sciences.

Azaphosphinate Dyes: A Low Molecular Weight Near-Infrared Scaffold for Development of Photoacoustic or Fluorescence Imaging Probes.

Near-infrared (NIR) dyes are desirable for biological imaging applications including photoacoustic (PA) and fluorescence imaging. Nonetheless, current NIR dyes are often plagued by relatively large molecular weights, poor water solubility, and limited photostability. Herein, we provide the first examples of azaphosphinate dyes which display desirable properties such as low molecular weight, absorption/emission above 750 nm, and remarkable water solubility. In PA imaging, an azaphosphinate dye exhibited a 4.1-fold enhancement in intensity compared to commonly used standards, the ability to multiplex with existing dyes in whole blood, imaging depths of 2.75 cm in a tissue model, and contrast in mice. An improved derivative for fluorescence imaging displayed a >10-fold reduction in photobleaching in water compared to the FDA-approved indocyanine green dye and could be visualized in mice. This new dye class provides a robust scaffold for the development of photoacoustic or NIR fluorescence imaging agents.

Advances in the synthesis of gold nanoclusters (AuNCs) of proteins extracted from nature

Abstract Over the past few decades, nanotechnology has developed rapidly and has been applied to various fields. Gold nanoclusters (AuNCs), which are composed of several hundred atoms, are a new type of nanomaterial. AuNCs are often synthesized using ligands or templates. The interaction between the gold atoms and the groups of the ligands or templates results in unexpected physical and chemical properties. In recent studies, natural proteins have often been used as templates to synthesize AuNCs. The unique structure of natural proteins endows AuNCs with biological functions, such as biocompatibility and enzymatic activity. The unique properties of these natural protein-AuNCs have been verified and applied in various fields. In this article, the synthetic strategies used to produce AuNCs have been divided into two categories: animal-derived and plant-derived protein synthesis. The protein types and synthesis strategies used in the current mainstream research are reviewed, and their applications in detection and biological imaging are summarized. Finally, the problems and future development directions of AuNCs synthesized from natural proteins are discussed, laying a foundation for the biological application of protein-AuNCs.

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

Efficient deep-red Aggregate-Induced emission material and “Hot-exciton” electroluminescence

Organic deep-red fluorescent materials have a wide range of applications in organic light-emitting diodes (OLEDs), biological imaging, night-vision equipment, and other fields. Here, we designed and synthesized a new deep-red emissive donor–acceptor (D-A) compound TPANZPPICN, whose non-doped OLED achieves stable pure deep-red electroluminescence (EL) at 692 nm with a maximum external quantum efficiency (EQE) of 2.67 % in non-doped OLED and a maximum EQE of 7.96 % at 660 nm in doped OLED. Magneto-electroluminescence (MEL) measurements reveal a negative response in the doped OLED, which is a significant character of reversed intersystem crossing (RISC) on high-lying excited states. Both theoretical calculations and experimental results confirm that the hot-exciton mechanism is responsible for the high efficiency EL of doped OLED, which proves to be a novel approach to realize the efficient deep-red organic fluorescent OLEDs.

PE-RASP: range image stitching of photon-efficient imaging through reconstruction, alignment, stitching integration network based on intensity image priors.

Single photon imaging integrates advanced single photon detection technology with Laser Radar (LiDAR) technology, offering heightened sensitivity and precise time measurement. This approach finds extensive applications in biological imaging, remote sensing, and non-visual field imaging. Nevertheless, current single photon LiDAR systems encounter challenges such as low spatial resolution and a limited field of view in their intensity and range images due to constraints in the imaging detector hardware. To overcome these challenges, this study introduces a novel deep learning image stitching algorithm tailored for single photon imaging. Leveraging the robust feature extraction capabilities of neural networks and the richer feature information present in intensity images, the algorithm stitches range images based on intensity image priors. This innovative approach significantly enhances the spatial resolution and imaging range of single photon LiDAR systems. Simulation and experimental results demonstrate the effectiveness of the proposed method in generating high-quality stitched single-photon intensity images, and the range images exhibit comparable high quality when stitched with prior information from the intensity images.

Low-cost single-shot complex optical field imaging with a simplified aperture

We report a new computational imaging methodology for complex optical field based on a single-frame diffraction intensity pattern acquisition with a simplified aperture and an extremely low-cost industrial machine vision camera. The current design of the apertures for the recovery of complex optical field was suffering from specific coding associated with the use of spatial light modulator or digital micromirror device, where it is difficult to make the optical implementations compact and cost-effective. In this work, we demonstrate that a simplified aperture without any pattern-like coding is efficient to establish the physical constraint for computational reconstruction. The aperture attached to the object defines the imaging region of interest (ROI) with coherent trans-illumination, and only one snapshot of the diffraction intensity pattern is required for recovering the ROI's complex field. Proof-of-concept numerical simulations and optical experiments have been carried out to validate the feasibility, noise robustness, resolution, and potential biological imaging applications of the proposed computational method.

Preparation of rare earth-doped nano-fluorescent materials in the second near-infrared region and their application in biological imaging.

Second near-infrared (NIR-II) fluorescence imaging (FLI) has gained widespread interest in the biomedical field because of its advantages of high sensitivity and high penetration depth. In particular, rare earth-doped nanoprobes (RENPs) have shown completely different physical and chemical properties from macroscopic substances owing to their unique size and structure. This paper reviews the synthesis methods and types of RENPs for NIR-II imaging, focusing on new methods to enhance the luminous intensity of RENPs and multi-band imaging and multi-mode imaging of RENPs in biological applications. This review also presents an overview of the challenges and future development prospects based on RENPs in NIR-II regional bioimaging.

The utilization of quantum dot labeling as a burgeoning technique in the field of biological imaging.

Quantum dots (QDs), with their unique optical and physical properties, have revolutionized the field of biological imaging, providing researchers with tools to explore cellular processes and molecular interactions in unprecedented detail. This review explores the diverse properties of QDs, emphasizing their application in biological imaging and addressing both their advantages and challenges. We discuss the developments in QD technology that have facilitated their integration into bioimaging, highlighting the role of surface modifications in enhancing their biocompatibility and functionality. The varied applications of QDs in both in vitro and in vivo imaging settings are examined, showcasing their capacity to deliver brighter, more stable, and multiplexed imaging solutions compared to traditional fluorescent dyes. Furthermore, we delve into the challenges associated with QD use, particularly concerns regarding their potential toxicity and long-term effects on biological systems, and explore ongoing research aimed at mitigating these issues. Finally, we discuss future directions in QD technology, anticipating advancements that will further solidify their role in biological imaging and open up new avenues for scientific exploration.

Polyhedral oligomeric silsesquioxane (POSS)-silicon/carbon quantum dots nanocomposites for cell imaging.

Silicon quantum dots (SiQDs) and carbon quantum dots (CQDs) are renowned for their outstanding applications in fluorescence imaging and biosensing. However, their small size poses significant challenges in terms of preparation, collection, and purification. Polyhedral oligomeric silsesquioxanes (POSS), an organic-inorganic nanohybrid with a cage-like structure, has recently attracted considerable attention due to its excellent biocompatibility. In this research, we utilize the encapsulating properties of POSS to improve the optical property of SiQDs/CQDs through an in situ synthesis strategy, resulting in the production of blue-emitting POSS-SiQDs, green-emitting POSS-G-CNDs, and red-emitting POSS-R-CNDs. By examining their structural and optical characteristics, it is found that these hybrid materials exhibit excellent luminescent properties, biocompatibility and cell membrane permeability. This facilitates multicolor intracellular imaging and underscores their successful application in biological imaging. Our study presents a novel approach to synthesize POSS-QDs composite nanomaterials with new perspectives in biological imaging and medical diagnostics.

A highly specific benzothiazole-based Schiff base for the ratiometric detection of hypochlorite (ClO−) ions in aqueous systems: a real application in biological imaging

This study describes the synthesis of a benzothiazole-salicylaldehyde Schiff base probe 1 for detection of ClO− ions.

C9-Aryl-substituted berberine derivatives with tunable AIE properties for cell imaging application.

Berberine (BBR), a widely used isoquinoline alkaloid derived from natural sources, exhibits aggregation-induced emission (AIE) characteristics and has biological applications such as in selective lipid droplet imaging and photodynamic therapy. However, natural BBR suffers from low fluorescence quantum yield (ΦF) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced ΦF up to 36% in the solid state. Interestingly, berberine derivatives containing an amino or a pyridyl group can exhibit fluorescence response to TFA. Cell imaging of the berberine derivatives was conducted using Caco-2 cancer cells, demonstrating their multi-color and efficient wash-free imaging capabilities. This work presents a new strategy for developing novel berberine derivatives with tunable AIE properties for application in biological imaging.

Construction of a novel isopinocamphone-based fluorescent probe for rapid and specific detection of ClO− and its application in environmental analysis and biological imaging

A “turn on” fluorescent probe DMTI was designed for the detection of ClO− based on isopinocamphone.

Tunable achromatic metalens for generating focused vortex beam in the near-infrared range

Highly precise and controllable focusing of optical vortex beams in the NIR range is essential for applications in biological imaging, nanomanipulation, and other fields. However, achieving tunable vortex beams across a broad spectrum remains a significant challenge. Herein, we propose a varifocal and broadband achromatic metalens capable of effectively correcting chromatic aberration, achieving a maximum focusing efficiency of 40.0% over 1400–1700 nm. Furthermore, through adjustments to the crystalline fraction of Ge2Sb2Te5 (GST), it offers the ability to vary focal lengths from 6.90 to 10.73 μm. This study may further advance NIR communication and imaging systems.

Fourier ptychographic microscopy image stack reconstruction using implicit neural representations

Image stacks provide invaluable 3D information in various biological and pathological imaging applications. Fourier ptychographic microscopy (FPM) enables reconstructing high-resolution, wide field-of-view image stacks without z-stack scanning, thus significantly accelerating image acquisition. However, existing FPM methods take tens of minutes to reconstruct and gigabytes of memory to store a high-resolution volumetric scene, impeding fast gigapixel-scale remote digital pathology. While deep learning approaches have been explored to address this challenge, existing methods poorly generalize to novel datasets and can produce unreliable hallucinations. This work presents FPM-INR, a compact and efficient framework that integrates physics-based optical models with implicit neural representations (INRs) to represent and reconstruct FPM image stacks. FPM-INR is agnostic to system design or sample types and does not require external training data. In our experiments, FPM-INR substantially outperforms traditional FPM algorithms with up to a 25-fold increase in speed and an 80-fold reduction in memory usage for continuous image stack representations.

Novel imidazo[1,2,4] triazole derivatives: Synthesis, fluorescence, bioactivity for SHP1

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1PTP at the concentration of 100 μM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe3+ ions, good anti-interference and relatively low detection limit (5.55 μM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1.

Exchangeable Self-Assembled Lanthanide Antennas for PLIM Microscopy.

Lanthanides have unique photoluminescence (PL) emission properties, including very long PL lifetimes. This makes them ideal for biological imaging applications, especially using PL lifetime imaging microscopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lanthanide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous-soluble, lanthanide antenna, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self-assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self-assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well-established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging.