A method for high-speed manipulation and detection of living cells

Abstract

The invention discloses a method for high-speed operation and detection of living cells, belonging to the technical field of double optical combs and optical tweezers. The method includes the following steps, step 1: obtaining a single-cavity mode multiplexing dual optical comb; step 2: using a photon lantern to perform spatial mode separation and obtaining a vortex beam carrying orbital angular momentum; step 3: operating tiny particles or living cells; Use the vortex beam obtained in step 2 to capture tiny particles or living cells with a diameter in the range of 10-50 μm, and then move and rotate the trapped tiny particles or living cells; step 4: measure the spectrum of the dual optical comb. The spectrum measurement speed of the method proposed in the present invention is fast, and the cell detection speed of millisecond level can be realized; the signal-to-noise ratio of the cell absorption spectrum measurement is high, the coherence of the dual optical comb is good, and the signal-to-noise ratio can be further improved by multiple averaging; The optical comb spectrum covers a wide range, and the same instrument can realize the identification and screening of multiple cells, providing a powerful tool for applications in various scenarios.

Description

technical field [0001] The invention relates to the technical field of double optical combs and optical tweezers, in particular to a method for high-speed operation and detection of living cells. Background technique [0002] Optical tweezers, as a tool that utilizes a strong focused light field to generate gradient forces to capture particles, can detect the single-molecule structure and function of living cell substances, and plays an important role in human exploration of the essence of life. [0003] The laser optical tweezers Raman spectroscopy technology that combines laser optical tweezers with confocal Raman spectroscopy can capture, manipulate and measure a single living cell in suspension under physiological conditions, and conduct biological analysis on it. The fingerprint information of molecular structure and material composition can realize high-resolution rapid label-free detection and analysis at the level of biomolecules. Although laser tweezers Raman spect...

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Problems solved by technology

Although laser tweezers Raman spectroscopy has many advantages, it also has many shortcomings: First, the literature [1] J.W.Chan, "Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free analysis of single cells," In Journal of Biophotonics 6,36-48(2013). Due to the extremely weak Raman scattering signal of biomolecules, the imaging extraction time is 1-10s per pixel or even longer, so it usually takes 10 minutes for a single living cell, which greatly limits the Raman scattering is applied to the research of in vivo imaging of living cells and monitoring the growth changes of living cells; secondly, as a nonlinear spectroscopy technique, Raman spectroscopy generally needs to increase the laser intensity to increase the intensity of Raman signal, which will not be possible. Avoid undesired effects on biomolecular activity

[0004] Literature [2] S.Feng, Z.Li, G.Chen, D.Lin, S.Huang, Z.Huang, Y.Li, J.Lin, R.Chen, and H.Zeng, "Ultrasound-mediated method for Rapid delivery of nano-particles into cells for intracellular surface-enhanced Raman spectroscopy and cancer cellscreening," Nanotechnology 26, 065101 (2015). It is mentioned that the surface-enhanced Raman scattering technology can effectively improve the Raman signal intensity to a certain extent, but the technology Generally, the distance between the sample to be tested and the designed micro-nano structure needs to be close enough, which is not suitable for live cell detection

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