Issue 1 2021

86 Acquisition International - Issue 1 2021 Nov20845 Compact Femtosecond Laser Provides Optical Skin Biopsies Words by Karsten König of JenLab GmbH enLab pioneered clinical multiphoton tomography (MPT) for the label-free, high-resolution in vivo evaluation of human skin. MPT is based on near infrared femtosecond laser pulses. So far, expensive bulky tomographs with a weight of more than 250 kg have been used based on tunable titanium: sapphire lasers with water- cooling. The laser light has to be transmitted through an optical arm. In 2021, JenLab introduced the clinically tested compact multimodal multiphoton tomograph MPT compact . The 120 kg tomograph employs a chiller-free femtosecond fiber laser at 780 nm that is located inside the measurement head. An optical arm is not required. Furthermore, the novel tomograph is a multimodal imaging system that can be used out in the field based on battery power. (Fig. 1) The tomograph MPT compact provides in a first step a 10x10mm 2 surface image of the suspicious skin. Then the doctor decides from what region of interest (0.3x0.3mm 2 ) he would like to get 3D information with subcellular resolution. Now the laser starts to scan the upper layers of the skin and to image the cells in the epidermis with their nuclei and fluorescent mitochondria within seconds directly on the computer screen. 80 million laser pulses are applied per second. The signal comes from coenzymes and the pigment melanin. Then, the sub-micron laser spot scans the upper dermis and depicts the collagen and the elastin network. Typically, 20 optical sections in different tissue depths are provided within 20 seconds when using the confocal reflection mode and two minutes when using the autofluorescence mode. These non-invasively and label-free taken sections provide an optical biopsy that can be used for rapid diagnosis of pathological skin. (Fig. 2) Because the resolution is about one order better than the cell size, the doctor can get information on the cell’s morphology, on the volume of the nucleus with respect to the cell volume, and on cell-cell distances. This resolution of 300 nanometers is even better than the resolution of the conventional microscope used by the pathologist after fixation, slicing and staining of physically taken biopsies. Instead of waiting one week for the result of a pathologist, the dermatolgist has now a high- resolution 3D imaging tool to provide the diagnosis within minutes. For example, the aggressive black skin cancer malignant melanoma, can be identified by imaging the dentritic melanocytes. Interestingly, the pigment melanin provides a strong fluorescence signal when exposed to near infrared femtosecond laser light. In melanocytes, the pigment melanin is located around the nucleus and within the four or more dentritic arms. It is possible to visualize these fluorescent arms and the body with the novel tomograph. In normal skin, melanocytes occur on the junction between epidermis and dermis within the monolayer stratum basale only. J However, in the case of malignant melanoma, the number of melanocytes increases, and these cells occur now also within upper epidermal tissue layers and within the dermis. Therefore, a rapid early diagnosis of cancer can be provided, when the tomograph images melanocytes above or beneath the stratum basale . Currently, three clinical studies in California and Germany are conducted regarding the use of multiphoton tomographs for the early diagnosis of skin cancer, including malignant melanoma. The tomograph can also image the architecture of the network of the extracellular matrix proteins collagen and elastin. Unfortunately, both proteins are degrading with age and modify their network. Also, the ratio of elastin to collagen, called SAAID, is changing. The skin age value SAAID decreases with age. Cosmetic companies try to stop skin ageing and to enhance the SAAID ratio by the topical administration of anti-aging means. Multiphoton tomography provides SAAID values that show if a cosmetic cream has a positive anti-ageing effect or not. Leading cosmetic and pharmaceutical companies in Europe, the US, and Japan are using JenLab’s multiphoton tomographs. Figure 1 The multiphoton tomograph MPTflex- CARS with a tunable titanium-sapphire laser that requires water-cooling as well as an optical arm to transfer the laser beams to the skin (left). The novel tomograph MPT compact is based on an ultracompact chiller- free fiber laser located inside the measurement head (right). The tomograph works also in remote areas on battery power. Figure 2 Rapid in vivo optical biopsies can be obtained by label-free multiphoton tomography using near infrared femtosecond laser technology. The skin is sliced optically and provides high-resolution images for an in vivo histology within a few minutes. Address: Johann-Hittorf-Strasse 8, 12489 Berlin, Germany Email: koenig@jenlab.de | Website: www.jenlab.de Telephone: +49 30 6392 7740 | fax +49 30 6392 7744