基于回音壁模式微腔激光器的痕量生化成分检测

Trace biochemical detection based on whispering gallery mode microcavity lasers

激光是现代光学的支柱之一,具有良好的方向性、单色性、相干性以及高亮度.基于这些特点,激光在很多应用领域发挥重要作用,如激光雷达、光纤通信、激光武器、激光切割、激光美容等.回音壁模式光学微腔是一种新型谐振腔,与传统的法布里-珀罗谐振腔相比具有高品质因子、小型化的优势,可以实现光与物质的强相互作用,制作低阈值、窄线宽的微型激光器.由于回音壁模式光学微腔具有显著的腔外倏逝场,其表面的分子、颗粒可以显著地改变激光的波长、线宽、阈值、强度,是一个良好的用于生化检测的平台.本文介绍回音壁模式微腔激光器的基本性质、生化检测机理及其在单纳米颗粒检测、痕量生化成分检测、细胞标记、细胞内检测等方面的应用,并对其应用前景进行展望.

Laser is one of the pillar technologies in modern optics which bears high brightness, high coherence, good directionality and excellent monochromaticity. Since its invention by Maiman in 1960, it has been widely used in industrial production,imaging, precision measurement, sensing and so on. Three most important parameters of lasers are wavelength, bandwidth and threshold. These parameters, to a large extent, depend on the value Q/V, where Q stands for the quality factor of the laser cavity, and V stands for cavity’s effective mode volume. A large Q/V value means strong interaction between the optical gain medium and the optical field in the cavity, leading to narrow bandwidth and low threshold. The traditional laser is based on Fabry-Perot cavity which consists of two highly reflective mirrors. Though this technology is mature, it also suffers from several disadvantages including but not limited to low quality factor, large mode volume and low mechanical stability.With the advances in nanotechnology, an alternative optical cavity came into being which is called whispering gallery mode(WGM) microcavity. Different from Fabry-Perot cavity where optical wave bounce to-and-fro between two mirrors,the principle of the whispering gallery mode is to confine the optical wave near the round periphery of the cavity by total internal reflection. These cavities own extremely small mode volume(typically tens of micrometers in diameter or even less than ten micrometer) and ultra-high Q factor(the highest record reaches 1011), which result in a large Q/V value. This makes it easy to realize strong light-matter interaction inside the cavity which is suitable to produce laser. Currently, the WGM micro-laser has been realized in different kinds of cavities, these include microsphere, microtoroid, microbubble and so on. The optical gain medium shows abundant diversities involving fluorescent dye, fluorescent protein, rare earth element, quantum dot and so on.Compared with fluorescence, laser bears the advantages of high signal to noise ratio, high brightness and narrow linewidth. These advantages make laser more competitive in biochemical detection than fluorescence, especially the WGM micro-laser, whose optical property is highly sensitive to outer disturbance, and whose size is small enough for in vivo biodetection.The principle of WGM micro-laser biomedical detection can be simply classified as follows:(1) Mode splitting. The WGM microcavity sustains degenerate optical modes in two different directions, which are referred to as clockwise(CW)mode and counterclockwise(CCW) mode. When a nanoparticle attaches to a microcavity, it will lift up the degeneracy between these two modes leading to mode splitting phenomenon.(2) Mode shifting. When the outer refractive index is changed, for example by different concentration of biochemical elements, the resonance wavelength changes correspondingly.(3) Mode broadening. When the surface of a microresonator is covered by biochemical elements, it will get rough and the quality factor of the microcavity will degrade, leading to broadening of the mode’s linewidth.(4)Threshold variation. Like the principle of mode broadening, when the quality factor degrades, the lasing threshold will increase.(5) Intensity variation. When the fluorescent property of the optical gain medium is changed by biochemical elements, the laser intensity will change correspondingly.So far, the WGM micro-laser has been widely used in trace biochemical detection. For instance, it can detect human Ig G(detection limit as low as 1 ag/m L), DNA molecule(detection limit as low as 100 nmol/L) and so on. The microlaser can also be used to detect nanoparticles such as polystyrene nanosphere and influenza virus, the detection limit can reach single particle level. Cell tracking has also been realized by making WGM resonators endocytosed by living cells. By employing micro-disk resonators as small as 2–3 μm in diameter, several thousands of cancer cells in tumor tissue can be tracked simultaneously. Besides, the WGM micro-laser can also detect ultra-sound waves, protein solution concentration,refractive index, etc.