Disclosed are methods of detecting an analyte of interest comprising introducing a sample comprising an analyte of interest to an antibody or antibody fragment; incubating the sample and antibody or antibody fragment under conditions sufficient to allow binding of the analyte of interest to the antibody or antibody fragment; and detecting the binding of the analyte of interest to the antibody or antibody fragment using a label-free second harmonic detection system. Also disclosed are methods of screening and diagnosing using antibodies or antibody fragments and a label-free second harmonic detection system.