Protein Diffusion in Electroporation‐Based Biopsy: Quantifying Protein Transport From Human Skin for Skin Liquid Sampling With Electroporation

Electroporation-based biopsy (e-biopsy) enables minimally invasive extraction of tissue proteins without excision; however, the effective diffusion from tissue into the sampling medium, a key parameter required for this procedure, has not been quantified in human tissues. We coupled time-resolved aqueous sampling with a one-dimensional Fickian slab model to estimate apparent diffusion coefficients (D) for total proteins released from excised human skin biopsy samples: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and healthy skin (HST) following e-biopsy. Total protein concentrations were measured from 0.5 to 30 min. At baseline (0 V mm⁻¹), D clustered around 0.026-0.029 mm² min⁻¹ across tissues. ANOVA showed a significant effect of field strength on D (F = 5.782, p = 0.001), but not tissue type (p = 0.715) nor the interaction (p = 0.395). These first human measurements establish diffusion coefficients for protein release from skin and skin cancers and demonstrate tunability by pulsed electric field strength. Our results show that 80% of all extractable proteins can be recovered at 3-5 min after pulsed field application, emphasizing that sampling time is a critical parameter for e-biopsy protocol design.