Early reports demonstrated the feasibility of TLM for comparative studies of cultured cells and for monitoring living blood and lymph cells, cell division and reaction of cells to varying contents of electrolytes in perfusion chambers. The progress of tissue culture methods, phase-contrast microscopy (see below) and real-time imaging by TLM enabled scientists to overcome the major limitation of traditional microscopy preparation of very thin transparent samples, which required tissue fixation and did not make it possible to investigate living cells, let alone, and biological processes over time in the same sample. Importance of TLM as a new method in biological research was highlighted by Burton. In this part, we will briefly review some selected publications, which highlight the rapid development of TLM as a versatile discovery tool within the broad scope of modern biology and medicine. In the absence of up-to-date comprehensive review on TLM advances, our aim was to familiarize the readers with the current advances of TLM methodology and provide for the reference guide to the most interesting reports where TLM has been utilized both for biological research and clinical purposes. For this review, we focused on mammalian cell cultures, although TLM can also be efficiently employed to study prokaryotic cells and unicellular microorganisms. Introduction of phase-contrast microscopy in 1940s, development of fluorescent and multidimensional microscopy, flow cytometry and computational tools made live cell imaging a widespread approach and prompted scientists to consider TLM as an essential technique that carries an enormous promise for basic biological science and medicine. However, to be visible in the light microscope, the cells are to be subjected to fixation and staining, the processes that kill the cells. Live cell imaging and the first non-sophisticated TLM techniques were pioneered at the very beginning of the twentieth century. TLM allows scientists to observe cellular dynamics and behavior of the population of living cells as well as of the single living cell within the population. TLM is the technique of capturing the sequence of microscopic images at regular intervals. The related time-lapse photographyis more relevant to observing non-microscopic objects, such as plants and landscapes. Originally described as time-lapse cinemicrography (microphotography), the modern time-lapse microscopy(TLM) emerged as a powerful and continuously improving tool for studying the cellular processes and cell-cell interactions with the applications ranging from fundamental aspects of molecular and cell biology to medical practice.
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