PROJECT SUMMARY Over 2.5 million skin cancers are diagnosed annually in the United States, more than all other forms of cancers combined. Early diagnosis is critical; thus, we propose to develop a soft and wearable magnetoelastic microneedle patch (MMP) for non-invasive and rapid skin cancer screening. It could perform fast scanning of the spatial stiffness of skin lesions with depths of up to 5 mm. This concept is established on the basis of the PI’s prior success in discovering the giant magnetoelastic effect in soft matter (Nat. Mater. 2021, 20, 1670). With a fundamentally new working mechanism, the proposed soft MMP can cover a large detection area (7.7 cm2) and have a high spatial resolution (1 mm, trained with super-resolution algorithm), high framerate (2000 Hz), and ultrahigh sensitivity (<2 kPa). We hypothesize that the proposed soft MMP enables fast, non-invasive scanning of skin stiffness of both lesions and borders spatially, which can be used experimentally and/or in clinics for skin cancer early diagnosis and screening, longitudinal monitoring, and/or guiding cancer excisions. To test our hypothesis, we propose three aims. Aim 1: Scalable design and optimization of a soft MMP for fast spatial stiffness mapping. Aim 2: Validate the soft MMP via stiffness mapping in mice models with skin cancer. Aim 3: Validate the soft MMP via stiffness mapping in excised human skin cancer.