Electroporation-based proteome sampling ex vivo enables the detection of brain melanoma protein signatures in a location proximate to visible tumor margins

Abstract

A major concern in tissue biopsies with a needle is missing the most lethal clone of a tumor, leading to a false negative result. This concern is well justified, since needle-based biopsies gather tissue information limited to needle size. In this work, we show that molecular harvesting with electroporation, e-biopsy, could increase the sampled tissue volume in comparison to tissue sampling by a needle alone. Suggested by numerical models of electric fields distribution, the increased sampled volume is achieved by electroporation-driven permeabilization of cellular membranes in the tissue around the sampling needle. We show that proteomic profiles, sampled by e-biopsy from the brain tissue, ex vivo, at 0.5mm distance outside the visible margins of mice brain melanoma metastasis, have protein patterns similar to melanoma tumor center and different from the healthy brain tissue. In addition, we show that e-biopsy probed proteome signature differentiates between melanoma tumor center and healthy brain in mice. This study suggests that e-biopsy could provide a novel tool for a minimally invasive sampling of molecules in tissue in larger volumes than achieved with traditional needle biopsies.

Comparison of lipidomic profiles sampled with electroporation-based biopsy from healthy skin, squamous cell carcinoma, and basal cell carcinoma

“…Other needle biopsy methods such as fine-needle aspiration and core needle biopsy also eliminate the need for resection but are limited by needle size[46,47], and the need for increasing diagnostic accuracy requires more invasive procedures with larger needle diameters[48,49]. In contrast, the e-biopsy technique has demonstrated the ability to sample areas larger than an actual needle diameter[27], providing valuable site-specific information. This also stands in contrast to previous lipid analysis studies that relied on serum samples, lacking the specific spatial context.…”

“…The recent electroporation-based biopsy sampling technique, e-biopsy, that leverages cell permeabilization caused by electric fields for molecular harvesting, demonstrated its ability to sample molecular profiles that differentiate between cancerous and healthy skin[25–27]. Coupling this sampling method with UPLC-MS-MS, which has proven its ability to identify potential markers of skin cancer[18], provides a promising direction for high-throughput analysis of extractable molecules.…”

“…Here we perform a comparative analysis of the first high-throughput lipidomic profiling of cSCC, BCC, and healthy skin tissue using e-biopsy. These profiles were collected with the e-biopsy approach, thus adding to previous e-biopsy enabled profiling in transcriptomics, proteomics, and metabolomics[16,25–27].…”

High‐throughput lipidomic profiles sampled with electroporation‐based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma

“…Here we perform a comparative analysis of the first high‐throughput lipidomic profiling of cSCC, BCC, and healthy skin tissue using e‐biopsy. These profiles were collected with the e‐biopsy approach, thus adding to previous e‐biopsy enabled profiling in transcriptomics, proteomics, and metabolomics 16,25–27 …”

Proteome sampling with e-biopsy enables differentiation between cutaneous squamous cell carcinoma and basal cell carcinoma

“…We have previously developed protocols for targeted delivery of electric fields to tissues to induce focused electroporation at predetermined regions in organs 23 . More recently, we have shown that electroporation-based molecular sampling, termed "e-biopsy", selectively extracts liquids from solid tissues with informative proteomes in animal models in liver cancer 24 and brain melanoma 25 in vitro and from breast cancer in vivo, enabling in vivo spatial mapping of differential protein expression 26 . To the best of our knowledge, such a technology…”