Spontaneous Particle Ordering, Sorting, and Assembly on Soap Films.

Soap bubbles exhibit abundant fascinating phenomena throughout the entire life of evolution with different fundamental physics governing them. Nevertheless, the complicated dynamics of small objects in soap films are still unrevealed. Here, we report the first observation of spontaneous particle ordering in a complicated galaxy of soap films without any external energy. The balance of interfacial tension at two liquid-gas interfaces is theoretically predicted to govern belted wetted particles (BWPs) traveling along a specified path spontaneously. Such spontaneous particle path-finding is found to depend on the particle size and hydrophilic properties. Spontaneous particle sorting is directly realized via these discrete and distinctive paths for different particles. The deformation of the soap membrane facilitates 1D/2D particle organization along the path. This observation represents the discovery of a new spontaneous order phenomenon in soap film systems and provides a new energy-free approach for particle separation and soft colloidal crystal assembly.

In Situ Single-Cell Surgery and Intracellular Organelle Manipulation Via Thermoplasmonics Combined Optical Trapping.

Microsurgery and biopsies on individual cells in a cellular microenvironment are of great importance to better understand the fundamental cellular processes at subcellular and even single-molecular levels. However, it is still a big challenge for in situ surgery without interfering with neighboring living cells. Here, we report a thermoplasmonics combined optical trapping (TOT) technique for in situ single-cell surgery and intracellular organelle manipulation, without interfering with neighboring cells. A selective single-cell perforation was demonstrated via a localized thermoplasmonic effect, which facilitated further targeted gene delivery. Such a perforation was reversible, and the damaged membrane was capable of being repaired. Remarkably, a targeted extraction and precise manipulation of intracellular organelles were realized via the optical trapping. This TOT technique represents a new way for single-cell microsurgery, gene delivery, and intracellular organelle manipulation, and it provides a new insight for a deeper understanding of cellular processes as well as to reveal underlying causes of diseases associated with organelle malfunctions at a subcellular level.

Optically Controlled Living Micromotors for the Manipulation and Disruption of Biological Targets.

Bioinspired and biohybrid micromotors represent a revolution in microrobotic research and are playing an increasingly important role in biomedical applications. In particular, biological micromotors that are multifunctional and can perform complex tasks are in great demand. Here, we report living and multifunctional micromotors based on single cells (green microalgae: Chlamydomonas reinhardtii) that are controlled by optical force. The micromotor's locomotion can be carefully controlled in a variety of biological media including cell culture medium, saliva, human serum, plasma, blood, and bone marrow fluid. It exhibits the capabilities to perform multiple tasks, in particular, indirect manipulation of biological targets and disruption of biological aggregates including in vitro blood clots. These micromotors can also act as elements in reconfigurable motor arrays where they efficiently work collaboratively and synchronously. This work provides new possibilities for many in vitro biomedical applications including target manipulation, cargo delivery and release, and biological aggregate removal.

Single Upconversion Nanoparticle-Bacterium Cotrapping for Single-Bacterium Labeling and Analysis.

Detecting and analyzing pathogenic bacteria in an effective and reliable manner is crucial for the diagnosis of acute bacterial infection and initial antibiotic therapy. However, the precise labeling and analysis of bacteria at the single-bacterium level are a technical challenge but very important to reveal important details about the heterogeneity of cells and responds to environment. This study demonstrates an optical strategy for single-bacterium labeling and analysis by the cotrapping of single upconversion nanoparticles (UCNPs) and bacteria together. A single UCNP with an average size of ≈120 nm is first optically trapped. Both ends of a single bacterium are then trapped and labeled with single UCNPs emitting green light. The labeled bacterium can be flexibly moved to designated locations for further analysis. Signals from bacteria of different sizes are detected in real time for single-bacterium analysis. This cotrapping method provides a new approach for single-pathogenic-bacterium labeling, detection, and real-time analysis at the single-particle and single-bacterium level.

Escherichia coli-based biophotonic waveguides.

The rapid progresses in biological and biomedical applications with optical interfaces have motivated an ever-increasing demand for biocompatible and disposable photonic components. Generally, these biophotonic components are first integrated with biocompatible materials and then interfaced with biological samples, such as living cells, for biological use. Therefore, direct formation of biophotonic components using living cells is greatly desired because the cells would serve simultaneously as samples and optical elements for signal sensing and detection. Here, we report an optical strategy for direct formation of biophotonic waveguides (bio-WGs) with Escherichia coli. The experiments demonstrate that this facile optical strategy enables forming bio-WGs with different lengths and good light propagation performances while the propagating signal can be detected in real-time. This strategy offers a seamless interface between optical and biological worlds with natural materials and provides a new opportunity for direct sensing and detection of biological signal and information in biocompatible microenvironments.

Opto-Thermal-Tension Mediated Precision Large-Scale Particle Manipulation and Flexible Patterning.

Large-scale particle manipulation with single-particle precision and further flexible patterning into functional structures is of huge potentials in many fields including bio-optoelectronic sensing, colloidal lithography, and wearable devices. However, it is very challenging for the precision manipulation and flexible patterning of particles on complicated curved and functional substrates. In this work, opto-thermal-tension (OTT) mediated precision large-scale particle manipulation and flexible patterning based on soap film are reported. Flexible manipulation and subsequent patterning of particles with single-particle resolution is realized by optothermal regulated surface tension on soap films. Reconfigurable patterning of particle structures with different shapes as well as large-scale ordered structures (up to 2000 particles) with particle sizes spanning two orders of magnitude (0.5-20 µm) is realized using this OTT mediation method. Importantly, due to the high flexibility of soap films, the patterned large-scale particle structures can be non-destructively transferred to curved and rough substrates, including rough iron pipe surface, leaf and skin surface. This OTT mediated method provides a new method for precision large-scale particle manipulation and flexible patterning with high versatility on complicated functional substrates, with great potentials for optoelectronic and biophotonic sensing and wearable device design on different curved and rough functional substrates.

Light-controlled soft bio-microrobot.

Micro/nanorobots hold exciting prospects for biomedical and even clinical applications due to their small size and high controllability. However, it is still a big challenge to maneuver micro/nanorobots into narrow spaces with high deformability and adaptability to perform complicated biomedical tasks. Here, we report a light-controlled soft bio-microrobots (called "Ebot") based on Euglena gracilis that are capable of performing multiple tasks in narrow microenvironments including intestinal mucosa with high controllability, deformability and adaptability. The motion of the Ebot can be precisely navigated via light-controlled polygonal flagellum beating. Moreover, the Ebot shows highly controlled deformability with different light illumination duration, which allows it to pass through narrow and curved microchannels with high adaptability. With these features, Ebots are able to execute multiple tasks, such as targeted drug delivery, selective removal of diseased cells in intestinal mucosa, as well as photodynamic therapy. This light-controlled Ebot provides a new bio-microrobotic tool, with many new possibilities for biomedical task execution in narrow and complicated spaces where conventional tools are difficult to access due to the lack of deformability and bio-adaptability.

Neural stimulation and modulation with sub-cellular precision by optomechanical bio-dart.

Neural stimulation and modulation at high spatial resolution are crucial for mediating neuronal signaling and plasticity, aiding in a better understanding of neuronal dysfunction and neurodegenerative diseases. However, developing a biocompatible and precisely controllable technique for accurate and effective stimulation and modulation of neurons at the subcellular level is highly challenging. Here, we report an optomechanical method for neural stimulation and modulation with subcellular precision using optically controlled bio-darts. The bio-dart is obtained from the tip of sunflower pollen grain and can generate transient pressure on the cell membrane with submicrometer spatial resolution when propelled by optical scattering force controlled with an optical fiber probe, which results in precision neural stimulation via precisely activation of membrane mechanosensitive ion channel. Importantly, controllable modulation of a single neuronal cell, even down to subcellular neuronal structures such as dendrites, axons, and soma, can be achieved. This bio-dart can also serve as a drug delivery tool for multifunctional neural stimulation and modulation. Remarkably, our optomechanical bio-darts can also be used for in vivo neural stimulation in larval zebrafish. This strategy provides a novel approach for neural stimulation and modulation with sub-cellular precision, paving the way for high-precision neuronal plasticity and neuromodulation.

Wake-Riding Effect-Inspired Opto-Hydrodynamic Diatombot for Non-Invasive Trapping and Removal of Nano-Biothreats.

Contamination of nano-biothreats, such as viruses, mycoplasmas, and pathogenic bacteria, is widespread in cell cultures and greatly threatens many cell-based bio-analysis and biomanufacturing. However, non-invasive trapping and removal of such biothreats during cell culturing, particularly many precious cells, is of great challenge. Here, inspired by the wake-riding effect, a biocompatible opto-hydrodynamic diatombot (OHD) based on optical trapping navigated rotational diatom (Phaeodactylum tricornutum Bohlin) for non-invasive trapping and removal of nano-biothreats is reported. Combining the opto-hydrodynamic effect and optical trapping, this rotational OHD enables the trapping of bio-targets down to sub-100 nm. Different nano-biothreats, such as adenoviruses, pathogenic bacteria, and mycoplasmas, are first demonstrated to be effectively trapped and removed by the OHD, without affecting culturing cells including precious cells such as hippocampal neurons. The removal efficiency is greatly enhanced via reconfigurable OHD array construction. Importantly, these OHDs show remarkable antibacterial capability, and further facilitate targeted gene delivery. This OHD serves as a smart micro-robotic platform for effective trapping and active removal of nano-biothreats in bio-microenvironments, and especially for cell culturing of many precious cells, with great promises for benefiting cell-based bio-analysis and biomanufacturing.

MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration.

Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors - scaffold degradation behavior and miRNA release profile - on osteogenesis and bone formation is still poorly understood. Herein, we construct a series of miRNA-activated hydrogel scaffolds (MAHSs) generated by 3D printing with different crosslinking degree to screened the interplay between scaffold degradation and miRNA release in the osteoinduction activity both in vitro and in vivo. Although MAHSs with a lower crosslinking degree (MAHS-0 and MAHS-0.25) released a higher amount of miR-29b in a sustained release profile, they degraded too fast to provide prolonged support for cell and tissue ingrowth. On the contrary, although the slow degradation of MAHSs with a higher crosslinking degree (MAHS-1 and MAHS-2.5) led to insufficient release of miR-29b, their adaptable degradation rate endowed them with more efficient osteoinductive behavior over the long term. MAHS-1 gave the most well-matched degradation rate and miR-29b release characteristics and was identified as the preferred MAHSs for accelerated bone regeneration. This study suggests that the bio-adaptable balance between scaffold degradation behavior and bioactive factors release profile plays a critical role in bone regeneration. These findings will provide a valuable reference about designing miRNAs as well as other bioactive molecules activated scaffold for tissue regeneration.

Targeted delivery and controllable release of nanoparticles using a defect-decorated optical nanofiber.

Targeted drug delivery and controllable release are particularly beneficial in medical therapy. This work provides a demonstration of nanoparticles targeted delivery and controllable release using a defect-decorated optical nanofiber (NF). By using the NF, polystyrene particles (PSs) (713-nm diameter) suspended in water were successfully trapped, then delivered along the NF at an average velocity of 4.8 µm/s with the assistance of a laser beam of 980-nm wavelength at an optical power of 39 mW, and finally, assembled at the defect. Subsequently, by turning off the optical power, 90% of the assembled PSs can be released in 30 s. This method would be useful in targeted drug delivery and controllable release, and provide potential applications in targeted therapy.

Massive photothermal trapping and migration of particles by a tapered optical fiber.

A simple but highly efficient method for particles or bacteria trapping and removal from water is of great importance for local water purification, particularly, for sanitation. Here, we report a massive photothermal trapping and migration of dielectric particles (SiO2, 2.08-µm diameter) in water by using a tapered optical fiber (3.1-µm diameter for taper). With a laser beam of 1.55 µm (170 mW) injected into the fiber, particles moved towards the position, which is about 380 µm away from the tip of the fiber, and assembled at a 290 µm × 100 µm spindle-shaped region. The highest assembly speed of particles is 22.1 ind./s and the highest moving velocity is 20.5 µm/s, which were induced by both negative photophoresis and temperature gradient. The number of assembled particles can reach 10,150 in 15 minutes. With a move of the fiber, the assembled particles will also migrate. We found that, when the fiber was moved 172 µm away from its original location, almost all of the assembled 10,150 particles were migrated to a new location in 140 s with a distance of 172 µm from their original location.

Photothermal trapping of dielectric particles by optical fiber-ring.

The removal of dielectric particles and bacteria from water is an extremely important global issue, particularly, for drinking and sanitation. This work provides a demonstration of optical purification of water using an optical fiber-ring. The size of particles suspended in water for trapping is 2.08 µm in diameter and the wavelength of light used for inducing photothermal effect is 1.55 µm with a power of 97 mW. The fiber, 6 µm in diameter, was formed to a racket-shaped ring with a minimum diameter of 167 µm and a maximum one of 350 µm. Experiment indicates that the particles moved toward the ring with the highest velocity of 4.2 µm/s and are trapped/assembled in the center of the ring once the laser beam of 1.55-µm wavelength was launched into the fiber. With a moving of the fiber-ring, the trapped/assembled particles were moved and the water can be purified by removal of the particles.

Biophotonic probes for bio-detection and imaging.

The rapid development of biophotonics and biomedical sciences makes a high demand on photonic structures to be interfaced with biological systems that are capable of manipulating light at small scales for sensitive detection of biological signals and precise imaging of cellular structures. However, conventional photonic structures based on artificial materials (either inorganic or toxic organic) inevitably show incompatibility and invasiveness when interfacing with biological systems. The design of biophotonic probes from the abundant natural materials, particularly biological entities such as virus, cells and tissues, with the capability of multifunctional light manipulation at target sites greatly increases the biocompatibility and minimizes the invasiveness to biological microenvironment. In this review, advances in biophotonic probes for bio-detection and imaging are reviewed. We emphatically and systematically describe biological entities-based photonic probes that offer appropriate optical properties, biocompatibility, and biodegradability with different optical functions from light generation, to light transportation and light modulation. Three representative biophotonic probes, i.e., biological lasers, cell-based biophotonic waveguides and bio-microlenses, are reviewed with applications for bio-detection and imaging. Finally, perspectives on future opportunities and potential improvements of biophotonic probes are also provided.

Optical Fiber Tweezers: A Versatile Tool for Optical Trapping and Manipulation.

Optical trapping is widely used in different areas, ranging from biomedical applications, to physics and material sciences. In recent years, optical fiber tweezers have attracted significant attention in the field of optical trapping due to their flexible manipulation, compact structure, and easy fabrication. As a versatile tool for optical trapping and manipulation, optical fiber tweezers can be used to trap, manipulate, arrange, and assemble tiny objects. Here, we review the optical fiber tweezers-based trapping and manipulation, including dual fiber tweezers for trapping and manipulation, single fiber tweezers for trapping and single cell analysis, optical fiber tweezers for cell assembly, structured optical fiber for enhanced trapping and manipulation, subwavelength optical fiber wire for evanescent fields-based trapping and delivery, and photothermal trapping, assembly, and manipulation.

Optical Forces: From Fundamental to Biological Applications.

Optical forces, generally arising from changes of field gradients or linear momentum carried by photons, form the basis for optical trapping and manipulation. Advances in optical forces help to reveal the nature of light-matter interactions, giving answers to a wide range of questions and solving problems across various disciplines, and are still yielding new insights in many exciting sciences, particularly in the fields of biological technology, material applications, and quantum sciences. This review focuses on recent advances in optical forces, ranging from fundamentals to applications for biological exploration. First, the basics of different types of optical forces with new light-matter interaction mechanisms and near-field techniques for optical force generation beyond the diffraction limit with nanometer accuracy are described. Optical forces for biological applications from in vitro to in vivo are then reviewed. Applications from individual manipulation to multiple assembly into functional biophotonic probes and soft-matter superstructures are discussed. At the end future directions for application of optical forces for biological exploration are provided.

Amplitude Holographic Interference-Based Microfluidic Colorimetry at the Micrometer Scale.

Quantitative molecular analysis is usually based on spectrophotometric methods using colorimetric assay. Conventional methods, however, rely on the direct uniform absorption of the sample under test, and the detection sensitivity is strictly limited by the length of the absorption cell at the millimeter scale. Here, we report a new methodology for colorimetric assay based on the amplitude holographic interference (AHI) caused by nonuniform absorption of light, with detection sensitivity at the micrometer scale. In our method, the curved surface of the microfluidics results in a phase profile with a high diffraction efficiency, and the nonuniform absorption of samples exactly matches with the amplitude modulation in the holographic interference. The signal intensity is affected by not only direct sample absorption but also the sequential optical interference behind the liquid level. Both single- and multiple-wavelength colorimetric analyses of the Griess-Saltzman dye (GSD) were carried out using this method, and we found that the sensitivity can be improved by approximately 2-fold in comparison to the conventional method. This interference-based method would be a useful tool for the colorimetric assay of chemical samples in highly integrated systems with better performance.

A fractionation procedure for identifying novel proteins induced by chill stress in Arabidopsis thaliana.

Extraction of plant proteins using typical extraction buffers leaves insoluble debris that cannot be investigated by conventional 2-DE technologies. In this paper, we present a scalable, off-line procedure for extraction of Arabidopsis thaliana homogenates that can be used in combination with both in-gel digestion and mass spectrometry. Based on sequential NaCl gradients and strong detergent fractionation, this new strategy allowed detection of 11 novel proteins from Arabidopsis thaliana that were altered in response to chilling stress.

Quantum biological tunnel junction for electron transfer imaging in live cells.

Quantum biological electron transfer (ET) essentially involves in virtually all important biological processes such as photosynthesis, cellular respiration, DNA repair, cellular homeostasis, and cell death. However, there is no real-time imaging method to capture biological electron tunnelling in live cells to date. Here, we report a quantum biological electron tunnelling (QBET) junction and its application in real-time optical detection of QBET and the dynamics of ET in mitochondrial cytochrome c during cell life and death process. QBET junctions permit to see the behaviours of electron tunnelling through barrier molecules with different barrier widths. Using QBET spectroscopy, we optically capture real-time ET in cytochrome c redox dynamics during cellular apoptosis and necrosis in living cells. The non-invasive real-time QBET spectroscopic imaging of ET in live cell open a new era in life sciences and medicine by providing a way to capture spatiotemporal ET dynamics and to reveal the quantum biological mechanisms.

Living Nanospear for Near-Field Optical Probing.

Optical nanoprobes, designed to emit or collect light in the close proximity of a sample, have been extensively used to sense and image at nanometer resolution. However, the available nanoprobes, constructed from artificial materials, are incompatible and invasive when interfacing with biological systems. In this work, we report a fully biocompatible nanoprobe for subwavelength probing of localized fluorescence from leukemia single-cells in human blood. The bioprobe is built on a tapered fiber tip apex by optical trapping of a yeast cell (1.4 µm radius) and a chain of Lactobacillus acidophilus cells (2 µm length and 200 nm radius), which act as a high-aspect-ratio nanospear. Light propagating along the bionanospear can be focused into a spot with a full width at half-maximum (fwhm) of 190 nm on the surface of single cells. Fluorescence signals are detected in real time at subwavelength spatial resolution. These noninvasive and biocompatible optical probes will find applications in imaging and manipulation of biospecimens.