Application Of Terahertz Metamaterial Biosensor In The Detection Of Colorectal Cancer Markers

Colorectal cancer(CRC)is a common malignant tumor and one of the leading causes of cancer-related deaths worldwide.Early diagnosis and screening are the most effective methods for the treatment of colorectal cancer.Developing relevant biomarkers is an important strategy to realize the early detection of colorectal cancer.The existing detection methods have the problems of large sample consumption,time-consuming sample preparation,expensive equipment and low sensitivity.In order to solve these problems,this study proposes a new method for rapid diagnosis of colorectal cancer.This method has the unique advantages of small sample size,label free and nondestructive.Owing to their stability in body fluids,exosomes have attracted increased attention as CRC biomarkers for early diagnosis.Terahertz(THz)metamaterials(MMs)biosensors have been evaluated as an effective method for trace biomolecular detection due to their strong resonant interaction with biomolecules.To validate the potential of the plasma exosomes as a novel biomarker for the monitoring of CRC,we demonstrated a THz MMs biosensor for the detection of exosomes in this work.The specific contents for this paper are:1.The THz MMs biosensor was designed using a full wave electromagnetic simulation software based on the finite integration time domain(FITD)method.The sensitivity of low and high resonant frequency can reach 63 GHz/RIU and 103 GHz/RIU,respectively.Lastly,the biosensor samples were fabricated by the surface micromachining process,and the performance of the samples was tested by the terahertz time-domain spectroscopy(TDS)system.The experimental results show good agreement with the simulation.2.Exosomes used in the experiment are extracted by the instructions of Exosomes Isolation and Purification Kit,and identified by using transmission electron microscope(TEM),Western blot(WB)and nanoparticle tracking analysis(NTA).3.The detection of different substances by antibody modified the THz MMs biosensor was studied.Afp,Ca125,Ca199,Her2 and exosome samples(the maximum and minimum values of resonance frequency shift)were added to the biosensor of modified antibody,showing different changes of resonance frequency shift,indicating that the proposed sensor modification method has specific recognition ability for trace exosomes(P<0.05).4.To study the application of antibody modified the THz MMs biosensor in the detection of colorectal cancer exosomes.The exosomes covered with colorectal cancer patients and healthy controls showed different resonant frequency shift changes,indicating that the terahertz metamaterial biosensor can distinguish colorectal cancer patients from healthy controls(P<0.05).The THz MMs biosensor has highly sensitive,highly specificity,and repeatability,and has great application potential in the research and development of modern diagnostic instruments.