State-of-the-art and Problems in Development of Automated Screening Systems in Personalized Medicine and Oncology

State-of-the-art and Problems in Development of Automated Screening Systems in Personalized Medicine and Oncology

Petersen E.; Gorbachev R.; Skorova E.; Volkov I.

Despite the fact that oncology issues are among the most actively studied, the problem of tumor resistance to the therapy remains very relevant at the moment. Currently, there are no validated models while known systems are generally focused ondetecting few particular conditions – either to assess the composition of the gaseous medium, humidity and temperature, or to assess the dissolved gases and pH in the flowing nutrient medium of bioreactors, or to assess the content of intracellular oxygen. These systems lack tracking of the dynamic parameters of 3D systems and the ability to operate such systems, including decision-making modules. To validate advanced cellular tumor models, one needs a device that should have advantages over modern commercially available models, this system has to be better in terms of sterile work, autonomy, cost-effectiveness, applicability for experiments and microscopy. Based on several types of physical, chemical and biological sensors, the new generation screening system will allow one to reveal in the foreseeable future additional indicators of the functional activity of tumor cells and dependence on changes in the extracellular matrix, metabolic activity of cells during their growth, migration, transformation and response to therapy on the basis of personalized 3D cellular tumor model.

I. INTRODUCTION

Despite the fact that oncology issues are among the most actively studied, the problem of tumor resistance to thetherapy remains very relevant at the moment [1]. This is due to the fact that the therapeutic methods that exist at the moment have been developed without taking into account new information about the more complex multicomponent processes of malignant neoplasm formation, where, in addition to the primary genetic mutations, the changes in the microenvironment of these transformed cells play an important role. The more heterogeneous the tumor, the more difficult it is to select an adequate method of therapy. The degree of heterogeneity increases under conditions of subthreshold stress loading on cells. These parameters that differ from a tumor to a tumor depend more on the state of a particular organism than on the nature of the tumor, are handled by personalized medicine. Existing standard models, in particular studies on cancer cell lines in 2D conditions and animal studies, showed incomplete compliance with data obtained through personalized clinical trials [2]. Research in the field of medicine and biotechnology is based primarily on destructive methods at the moment, such as histology of immunohistochemistry, PCR and so on. This in turn contributes to the increase in the reliability error, since all biological objects, including native biomaterials, have a wide range of personal variability. A new approach in this direction could be based on nondestructive methods, with the use of biosensors and sensors [3, 4].
To develop personalized drugs with antitumor effect, effective screening platforms that include 3D cellular tumor models are needed. Currently, there are no validated models that make it possible to evaluate these parameters experimentally. Most of the systems developed so far are generally aimed at detecting conditions in any particular mode – either to assess the composition of the gaseous medium, humidity and temperature as in a CO2 incubator, or to assess the dissolved gases and pH in the flowing nutrient medium of bioreactors, or to assess the content of intracellular oxygen. All of these methods reflect different stages of the conditional “metabolism” or mass transfer of nutrients, metabolites and dissolved gases in biological objects. Thus in modern oncology there is a demand for inexpensive non-invasive screening methods for evaluation of morphological and functional changes to the multiparametric approach evaluation of anticancer therapy action with the ability to use the automated software decision support system.
Based on the practical considerations mentioned aboveand on the requirements for validating systems in modern oncology, it is possible to evaluate those characteristics that the device should ideally possess: non-invasiveness; budgetary; mobility and compatibility necessary to ensure the possibility of conducting research using various methods – biochemical, biophysical, optical; the use of feedback mechanisms based on biosensors to maintain an accurate equilibrium state of the system and the reproducibility of the experimental conditions; decision support systems, the possibility of adding biological substances and candidates required for screening; open source modular system, ensuring compatibility with different types of biological protocols.

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