基于锥形光纤光镊的细胞操控与神经调控

Cell Manipulation and Neuron Regulation Based on Tapered Optical Fiber Tweezers

光学操控已被广泛应用于生物医学、物理和材料科学等领域.近年来,锥形光纤光镊由于具有操作灵活、结构紧凑、易于制造等特点,在光学操控领域引起了极大关注.作为一种非侵入式光操控工具,锥形光纤光镊不会对生物组织和活体细胞产生接触式物理损伤,因而可以直接应用于细胞的多维度操控.此外,红外光波对生物组织具有良好的穿透性,这使得锥形光纤光镊在生物及医学领域有着不俗的表现.在这篇综述,笔者总结了锥形光纤光镊在单细胞、多细胞、亚细胞等层面的研究现状,并介绍了其在神经细胞调控方面的最新进展.

Significance Optical trapping is widely used in various fields ranging from biomedical applications to physics and material sciences.Recently,tapered optical fiber tweezers(TOFTs)have attracted significant attention in the optical trapping field owing to their flexible manipulation,compact structure,and ease of fabrication.As a non-invasive technique,TOFTs can be used to directly manipulate cells in multiple dimensions in different bio-microenvironments.In addition,infrared light waves penetrate biological tissues well,which enhances the performance of TOFTs technology in the biology and medicine fields.Here,we review TOFTbased trapping and manipulation at the single-,multi-,and sub-cellular levels,as well as the latest developments in neuron regulation.Progress Since Arthur Ashkin used two focused and counter-propagating beams to trap particles in 1970,optical forces have been widely used to manipulate and trap particles using laser beams.In 1986,Ashkin et al.discovered that a single tightly focused laser beam could achieve stable particle trapping.Subsequently,they named the optical-trapping technique as“optical tweezers,”which we now refer to as conventional optical tweezers(COTs).Over the years that followed,Ashkin et al.conducted numerous studies using a single focused laser beam for capturing particles ranging from tens of nanometers to tens of microns,including viruses and bacteria.Optical trapping and manipulation using COTs has undergone substantial progress regarding its methodologies and applications over the span of nearly 50 years.These techniques involve manipulating various samples,including dielectric particles,biological cells,and biomolecules.Nonetheless,focusing light via COTs requires a high-numerical-aperture(NA)objective along with diverse optical components for beam steering and expansion.Owing to its bulky structure,this framework remains deficient in control and manipulation flexibility.Alternatively,holographic optical tweezers(HOTs)were created in 1998 to allow the manipulation of multiple particles using complex-structured light fields.This technology uses computer-generated holograms through spatial light modulators to achieve multiple traps,thereby providing enhanced control and manipulation capabilities.However,trapping particles at the nanometer scale using HOTs remains challenging because of the diffraction limit.Surface-plasmon-based optical tweezers(SPOTs)were developed in the late 2000s to trap and manipulate nanoscale particles,including single molecules that are only a few nanometers in size.However,owing to their ability to trap nanoscale particles,the carefully designed and elaborated nanostructures necessary for SPOTs limit their flexibility.Techniques,such as COTs,HOTs,and SPOT,involve complex devices and components with inflexible control.Therefore,it is critical to develop simple and flexible manipulation tools.The advancements in optical fiber tweezers(OFTs)has made them versatile candidates for the optical trapping and manipulation of different samples.The simple structure of OFTs,consisting solely of optical fibers,provides them with exceptional advantages in terms of manipulation flexibility.OFTs can be easily inserted into thick samples and turbid media,significantly extending sample applicability.In addition,OFTs offer a low-cost solution because of their simple fabrication procedures.They can be integrated into small devices,such as optofluidic channels and chips,paving the way for a scaled-down approach.OFTs were first demonstrated in 1993 by employing two aligned single-mode fibers for optical trapping.Although tiny particles and cells can be directly captured and manipulated using the optical scattering force generated by two fibers,they also result in limited manipulation flexibility.A single optical fiber can also be used for particle trapping and manipulation.Single tapered optical fiber tweezers(TOFTs)were introduced in 1997 and have significantly improved the flexibility of optical manipulation.The end of a single fiber used for focusing the light beam is similar to that used in COTs after being drawn into a lenticular shape,which creates a stronger gradient force on the particle and facilitates optical trapping.Conclusions and Prospects In conclusion,this review highlights recent advancements in tapered optical fiber based tweezers for optical trapping and manipulation.Despite the significant progress,TOFTs still face numerous challenges.One of the major issues is the direct contact of the fiber end surface with the sample,which leads to mechanical damage.Thus,it is necessary to develop of noncontact and damage-free trapping techniques.Another critical area of concern is the stable trapping and manipulation of nanometersized samples that surpass the diffraction limits.TOFTs encounter difficulties in trapping individual biomolecules,which is of great importance for single-molecule analysis.Furthermore,optical trapping of cells and biological structures for biosensing in vivo is an upcoming trend;however,inserting fibers into living samples may cause mechanical damage.Hence,the construction of biocompatible TOFTs is crucial to maintain their application potential.Biophotonic waveguides composed of living cells enable the manufacturing of biocompatible optical fibers,making trapping,manipulation,sensing,and diagnostics feasible in vivo.On the other hand,TOFTs technology is constantly experiencing new breakthroughs owing to its combination with new technologies like artificial intelligence(AI)and spectral analysis,as well as new applications like neuromodulation and precision medicine.