Magdalena Swierczewska,^ab Gang Liu,^ac Seulki Lee^*a and Xiaoyuan Chen^*a

^aLaboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Dr 1C22, Bethesda, MD 20892, USA. ^bDepartment of Biomedical Engineering, Stony Brook University, Bioengineering Building, Stony Brook, NY 11794, USA 
^cSichuan Key Laboratory of Medical Imaging, North Sichuan Medical College, Nanchong 637007, China

Abstract
High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes.