In this special issue, latest laser technologies for medical applications in the post-corona era have been introduced from the viewpoint of observing and controlling biological molecules in living cells, tissues and organs. The topics of this issue cover two-photon fluorescence microscopy, light-sheet fluorescence microscopy, Raman imaging and spectroscopy, molecular imaging and manipulation, molecular-targeted phototherapy, and laser adjuvant.

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Recent advances in optics and laser technology have led to the development of visualization and analysis methods for cellular physiological functions. Two-photon microscopy, which is indispensable due to its minimal invasion of living specimens, is laser scanning fluorescence microscopy that utilizes two-photon excitation processes induced by near-infrared ultrashort laser pulses. We have been promoting the use of semiconductor lasers, adaptive optics, vector beams, and nanomaterials to improve the spatial resolution or the observation depth. We successfully visualized the activity of hippocampal CA1 neurons in the deep brain of mice at video rates without resecting the neocortex. We also proposed using fluoropolymer nanosheets for in vivo imaging and improved the spatial resolution by optical technologies based on adaptive optics.

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The scattering and diffraction of light limit biological stimulation or sensing performances. These fundamental limitations are an open challenge in the field of biomedical optics. A recently reported class of photoacoustic techniques addresses these challenges by non-invasively and actively manipulating the light propagation inside biological samples. To successfully control light propagation, laser-induced acoustic pulses produce a high refractive index contrast within samples without high-intensity pressure. This review summarizes the light-guiding principle and applications to deep-tissue fluorescence excitation and light-sheet fluorescence microscopy.

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In medicine, “visualization” plays an important role from basic science to medical practice in elucidating the aetiology and pathogenesis of disease and determining satisfactory treatment procedures in clinical practice. However, conventional visualization methods suffer from limitations, such as limited applicability to the human body and the inability to obtain the direct functional information of organs. Raman spectroscopy is a novel candidate as a human-applicable visualization method based on the evaluation of the functional information of organs by molecular vibrations. This article reviews the recent advances and potential of Raman spectroscopy in medical applications, especially for evaluating myocardial infarctions and non-alcoholic fatty liver disease.

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Neurons in a complex network communicate with each other through synaptic connections. Molecular dynamics, including cellular receptors and scaffolding proteins at synaptic terminals, are essential for synaptic transmission and the subsequent synaptic plasticity of the neuronal networks involved in learning and memory. The artificial control of synaptic transmission in neuronal networks requires a novel approach to accurately design perturbations into neurons at the single-cell level. Herein, we demonstrate the molecular manipulation of neurons by optical trapping with a focused laser beam. We evaluated molecular dynamics in an optical trap of cell surface molecules on neurons by fluorescence imaging and fluorescence correlation spectroscopy to achieve the reversible control of synaptic transmission in neuronal networks.

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Electromagnetic waves in the near-infrared (NIR) region have relatively high tissue permeability and are expected to be applied not only to small animals for research but also in human clinical practices. In molecular imaging, a molecular target probe is used to visualize the functions of the targeted molecules and find specific diseases. To date, various near-infrared fluorescence and photoacoustic imaging methods have been developed. Molecular-targeted phototherapy, or NIR-Photoimmuno therapy (PIT), was developed using photochemical reactions induced by near-infrared light and approved in Japan in 2020. In NIR-PIT, antibody-photoabsorber conjugates are used as a drug. NIR light specifically activates the drug on the cancer cell membrane, causing irreversible damage to the cell membrane.

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In a society where the epidemic of COVID-19 continues, the range of laser technology expected to be applied to medical treatment is wide. In order to enhance the efficacy of the vaccine inoculated intradermally, vaccine augmentation technology using a laser as a light source has been studied and is called a laser adjuvant.

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