Microscale Magnetic Imaging Of Tumor Tissues Using NV Centers In Diamond

Cancer is one of the major diseases that endanger human health.Research on its pathogenesis and clinical diagnostic methods have always been significant for biological and medical scientists.The elucidation of cancer pathogenesis and the development of new technologies are expected to improve the diagnosis and treatment of cancer.With the advent of Precision Medicine,personalized diagnosis and treatment require increasingly precise and sensitive tumor detection methods.Therefore,in addition to the technological advances in the biomedical field,it has become a meaningful and challenging task to realize technology transformation into tumor detection from other fields.In this thesis,we focus on a quantum magnetic sensor in diamond:the nitrogen-vacancy(NV)center.The NV center is a nanoscale crystal defect in diamond,which possesses excellent optical properties and magnetic sensing capabilities.Since the NV center was first proposed for nanoscale magnetic sensing in 2008,quantum precision measurement based on it has developed rapidly.Microscale magnetic resonance technology based on NV centers possesses characteristics of single-molecule sensitivity,nanometer resolution and good biocompatibility at room-temperature,which makes it especially suitable for biomedical research.After having been developed for more than a decade,NV centers have been broadly applied to biological research at the molecular,cellular,tissue,and individual scales.How the highly sensitive magnetic measurement capability of the NV center can be translated into practical and applicable tumor detection methods is the main focus of this thesis.Therefore,we built magnetic imaging platforms for micron and hundreds-micron spatial resolution respectively,and developed magnetic imaging methods for ex vivo tissue sections and an in vivo nondestructive detection method,respectively.The thesis is divided into two main parts as follows:1.Using two-dimensional NV centers in diamond,we have built a diamond magnetic microscope and achieved magnetic imaging of biological samples with 400nm spatial resolution.Based on conditional generative adversarial networks,we proposed and implemented a magnetic reconstruction method without distance information,which makes the accurate quantification of magnetic imaging possible.In addition,we developed immunomagnetic labeling and attachment techniques for tumor tissue sections.Eventually,we achieved magnetic imaging with submicron resolution and magneto-optical bimodal imaging at the tissue level,demonstrating the ability of magnetic imaging methods:low background,high sensitivity,high stability,and absolute magnetic quantification.This method,which fills the gap between conventional magnetic resonance imaging at the tissue level and micron resolution,complements the advantages of conventional optical imaging in histopathology.2.Pushing the ex vivo detection to the in vivo level is an important step for the development of tumor detection methods.To achieve in vivo magnetic imaging with hundreds-micron resolution,we have built a scanning magnetometer below a thousand gauss and combined techniques such as lock-in detection,drive modulation,and noise suppression methods based on common mode detection to enhance the magnetic measurement performance of the magnetometer.This device will be used to develop in vivo magnetic imaging technology and to explore its applications in skin tumors.