| Micro/nano robots are a kind of active particles with micro/nano structures,which can convert energy in the environment into mechanical energy and achieve active motion.Magnetically driven micro/nano robots have the advantages of the high biocompatibility and strong ion tolerance due to use the non-contact magnetic field force for self-propulsion.Magnetically driven micro/nano robots can be applied to more complex environments,suggesting the great potential in vivo application in future.The micro/nano robots,as an operable platform,show advantages in biochemical sensing in analytical chemistry and provide an alternative strategy for innovating the traditional biochemical sensing methods.This paper mainly explores the combination of the magnetically driven micro/nano robots with surface enhanced Raman spectroscopy（SERS）and enzyme-linked immunosorbent assay（ELISA）.Make full use of the size advantages and motion characteristics of MNRs to improve the detection efficiency and develop in vitro rapid diagnosis technology.At the same time,the magnetic helix micro robot is used to develop in vivo accurate sampling and labeled molecule detection technology.Firstly,we prepared the"rod-like"magnetic micro-robot SERS probe（MNR-SERS）by self-assembly technology.The main structure is composed of Fe3O4nanoparticles coated with silica.Silver nanoparticles were grown in situ on the surface of silica layer through silver-mirror reaction,which is used as SERS sensing hotspot of micro-robot.The MNR-SERS probe of the magnetic micro-robot can accurately arrive the target position according to the pre-designed route.Then actively rotation can accelerate the mixing of substances to enhance the contact between the SERS probe and the analyte for targeted SERS sen sing via remote operation.At the same time,using microfluidic-chip technology,we proved the self-cleaning ability and reusability of magnetic micro-robot SERS probe.The SERS probe can overcome the disadvantage of easily contamination of convention SERS probes.We further carried out biosensor in vitro.The MNR-SERS probe can accurately move to a single target cell and then enter the cell through endocytosis.After the rotation of the MNR-SERS probe in the intracellular environment,a significantly enhanced SERS signal with improved signal-to-noise ratio was obtained.Compared with non-rotating SERS probe,more additional Raman peaks of biomolecules in cytoplasm were captured,which provides a new way and method for further study of intracellular substances for biosensor analysis in the future.Then we combined the"rod-like"magnetic micro-robot as the operation platform with ELISA to solve the shortcomings of convention ELISA detection and obtain an efficient and automatic detection method.In the experi ment,the capture antibody was combined with the amino group on the silica surface of the"rod-like"magnetic micro-robot to form a mobile immunoassay probe（MNR-ELISA）.In the gradient magnetic field,MNR-ELISA can be guided to the target position and then the magnetic field was transformed into a rotating magnetic field to achieve uniform mixing.The MNR-ELISA has the advantage of one-dimensional structure,which can effectively stir the fluid,so as to significantly shorten the incubation time and improve the detection efficiency.At the same time,a detection unit composed of reaction well,cleaning well and detection well was designed in the experiment.Each functional wells are separated through the oil-water interface,which can overcome the interference of residual reagent.MNR-ELISA can automatically shuttle between different functional wells.In addition,the simulation results of the magnetic field distribution of Helmholtz coil in three-dimensional space proved that the MNR-ELISA is feasible for high flux diagnosis.Finally,in order to realize in-situ sampling and sensing detection based on micro-robot in vivo,a magnetically driven helix micro-robot was designed and prepared.Using the micro-motion platform,the growth range of Au nano spines can be controlled by partially dipping to selectively grow at the tip of helix micro-robot.In the experiment,we systematically studied the motion of helix micro robot in two-dimensional plane and a tubular capillary glass tube.In order to adapt to the complex fluid environment in the body,the motion of the helix micro-robot under different flow velocities were studied under the same and opposite direction of the flow field,respectively.The adaptability of the helix micro-robot in the flow field can be improved by increasing the rotation frequency of the driving magnetic field.Finally,a three-dimensional external blood vessel model was established in the experiment to study the control strategy and motion of the helix micro-robot in the simulated blood vessel.The Au nano-thorn structure at the tip of the helix micro-robot is used to sample the target position in the simulated blood vessel.At the same time,a hydrogen peroxide-responsive detection probe was constructed based on Au nano-thorns combined with 4-MBA reporter molecules to detect markers in the simulated tumor microenvironment.In this paper,“rod-like”magnetic drive micro/nano robot with controllable length is prepared by magnetic self-assembly.The helix magnetically driven micro robot with controllable morphology is prepared by surface projection printing technology.The electrical and hydrophobic properties on the surface of micro/nano robot can be changed by surface functional modification.The micro/nano robot is used as the operation platform to combined with SERS and ELISA.The self-propulsion and motion controllability of micro-robot are used to realize the rapid mixing of materials in micro/nano scale and accelerate the rapid combination of materials at the reaction interface.The magnetically driven micro/nano robot can be used as a general micro/nano operation and detection platform.It can be combined with different detection methods to achieve cross-molecular scale detection,which provides a new idea and general operation platform for efficient real-time detection in the future. |
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