Project Summary Expansion of tandem DNA repeats—trinucleotide repeats or TNR—cause more than fifty genetically transferrable disorders, which affect 4 million people every year. Current state-of-the-art diagnostic technologies for genetic testing for length mutations have their own limitations such as clogging of protein nanopores, requiring labelling steps, frequent false positive/negative results, or short basepair read length. To overcome the limitations that hamper the current biomedical science, there is a critical need to develop new platforms standing on rigorous basic science. The parent AREA award involves mainly undergraduate researchers to investigate intrinsic charge transfer character of tandem DNA repeats interfaced with MoS2 surfaces that may ultimately manifest into a label-free sensing platform in future. The project urgently needs a conductive atomic force microscope (C-AFM) to study the electrical charge transfer property of the interface to complement and validate electrochemical charge transfer behavior. Leveraging on theoretical and experimental studies, the PI hypothesizes that DNA repeats can produce sequence- and length-dependent label-free charge transfer signals due to the differential affinity of the nucleobases for molybdenum disulfide (MoS2). This is critical to study through a rigorous plan as detailed in the parent award. Currently, we are performing electrochemical measurements that have to be confirmed by surface probe microscopy techniques, such as C-AFM. In the specific aims, the PI plans to study 66 sequences of two different lengths and specifically (1) investigate sequence- dependent charge transport at TNR/MoS2 interface, and (2) investigate length-dependent charge transport at the interface. The experiments also involve studying the effects of sequence concentration and conformations. This supplement grant will train the undergraduate researchers on C-AFM technique which is a powerful surface probe technique used in surface chemistry and materials science researches. Ultimately, this supplement award will substantiate our electrochemical study in the parent award and provide a critical piece of information to develop a new and sensitive technology for the detection of length mutations.