Periodic Reporting for period 1 - SKIN-CANCER-PROBE (A novel handheld probe coupled to mass spectrometer as a non-invasive tool for fast in vivo diagnosis of skin cancer)
Berichtszeitraum: 2020-08-01 bis 2022-07-31
This project describes a sampler probe that can be used for sampling from the skin surface and can be coupled on-line with mass spectrometry for fast diagnosis of skin cancer. The probe is a handheld pen-like device with extractive phase coated rotating tip. The coated tip is selective for extraction of small molecules and can monitor the chemical differences present on the tissue. The working principle of the probe is based on exposure of the extractive tip of the probe for a certain time to the tissue surface and sequential analysis of the extract enriched with molecules in on-line mode with highly selective and sensitive electrospray ionization mass spectrometry (ESI-MS). In this study, the probe has been successfully used in vivo for detection of differentiating metabolites in mice with skin cancer.
Skin cancer is one of the main health issues affecting the entire population as the most commonly seen cancer. Early diagnosis of skin cancer is crucial, as five-year survival rates of “early detection of regional nonmetastatic cutaneous melanomas” is reported to be 98% while it drops to 16% for “distant and metastatic melanomas”. Malignancy diagnosis is done initially by dermatologists by visual inspection which often is open to misinterpretations between dysplastic nevi and melanoma. Therefore, the presence of melanoma is confirmed with histopathology which requires performing a biopsy, a very invasive procedure. Recently, it has been an effort to develop non-invasive methods that can be used for fast and reliable diagnosis of melanoma, including dielectric probe, pen-sized Raman spectroscopy probe, diffuse reflectance spectroscopic and laser-induced fluorescence spectroscopic approaches. However, due to lack of their specificity none of these novel methods provides sufficient sensitivity for early diagnosis and none of them is suitable for detection of unique biomarkers of skin cancer. Therefore novel, innovative, and reliable techniques that can be used for fast and non-invasive early diagnosis of skin cancer are in high demand. The main objective of the project is to develop a handheld probe that can be used directly on the skin and can be coupled with on-line mass spectrometric detection for fast and reliable diagnosis of skin cancer, here shown in mice model. As one of the most important health problems and being the most common cancer, the probe may provide in future a new platform for fast diagnosis of the skin cancer.
The handheld probe has been prepared using 3D printing technology. As the extractive phase, hydrophilic lipophilic polymer was synthesized and immobilized within biocompatible glue on the probe tip. The extractive properties of the probe were investigated by selected metabolites that can be found in biological system. The probe integration for on-line monitoring with direct mass spectrometric analysis has been optimized. Following the optimizations, the probe has been tested in mice cancer model. The results of the study indicated that the novel handheld probe can discriminate the chemical differences present in the biological system. Moreover, some small molecules were found as significantly different in the cancer model compared to control mice group. To enhance the selectivity of the probe towards the molecules that were found as significantly different, new materials with tuned properties for the selected metabolites were synthesized, characterized, and used for preparation of selective probes. The results of the study suggest that the developed probe is promising for fast diagnosis of the cancer directly from the intact tissue in vivo. The project outcomes have been shared in several academic seminars, lectures, and outreach activities.