Terahertz Time-domain Near-field Scanning Microscope For Glioma Detection

The energy of photon in terahertz range is around milli-electron volt,coincident with the energy gap between the biomolecules or their groups’ states of vibration,rotation,bending,etc.Therefore,terahertz wave has a low ionizing ability and terahertz-based techniques are relatively safe to living organisms.The present work provides an attempt of glioma detection based on terahertz time-domain near-field scanning microscope.This paper briefly introduces the basic design ideas and technical difficulties of the near-field imaging methods based on aperture,scattering and direct detection method,respectively,and tries to deduce the physical and mathematical principles of the direct detection method.The related principles involved in the design of terahertz time-domain spectroscopy are introduced,including the principle of complex refractive index measurement,photoconductive antenna and coherent detection.The technical details of optical path design,delay line and data acquisition,near-field probe and sample separation measurement,and cooperation of visible light microscope are discussed.This paper contains two main innovations.First,employing voice coil motor delay line and acquisition triggered by grating ruler position,we get a shorter signal acquisition time than the traditional stepping mode delay line and a more accurate signal waveform than the fixed sampling rate.Second,the automatic measurement of the separation between the near field probe and the sample is realized by using the image processing and feature extraction methods.Based on the terahertz time-domain near-field scanning microscope designed and built in this paper,the grating structures and biological samples were scanned in near-field.The imaging results of the grating structures show that the spatial resolution of the system is not bad than 20 μm.The imaging results of biological samples show that the spatial resolution superior to the diffraction limit can be obtained.Among them,the imaging results of glioma samples show that glioma and normal brain tissue can be distinguished.The imaging results of fat and muscle tissue show that fat and muscle areas can be distinguished.The imaging results of the brain tissue samples show that the regions of the corpus callosum and cerebral cortex can be separated,as well.This work provides a good example of imaging biological samples with the terahertz time-domain near-field scanning microscope,paving a new avenue of using advanced terahertz technique in biomedical researches.