Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

Precision or personalized medicine aims to determine an optimal therapy for each individual patient. In oncology techniques such as next generation sequencing, mRNA-sequencing, ChIP-sequencing, and mass spectrometry are used to perform a full molecular profiling for each patient. However, it is not always possible to determine a suitable treatment for an individual cancer based on molecular profiling, mostly due to the high level of tumor heterogeneity. In vitro drug sensitivity and resistance test (DSRT) can be performed on cancer cells or tissues obtained from a patient with a panel of anticancer compounds in order to experimentally define sensitivity and resistance of each individual cancer. In combination with molecular profiling, DSRT can provide a fuller picture about the nature of disease, allowing for finding more appropriate therapy for each individual patient. In this progress report, studies describing in vitro DSRTs on 2D and 3D cell models based on patient-derived cells are reviewed and challenges and future steps needed for the adaptation of these systems in clinics are discussed

Fast Nanoliter-Scale Cell Assays Using Droplet Microarray–Mass Spectrometry Imaging

In pharmaceutical research and development, cell‐based assays are primarily used with readout that rely on fluorescence‐based and other label‐dependent techniques for analysis of different cellular processes. Superhydrophobic–hydrophilic droplet microarrays (DMA) and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS) have recently emerged as key technologies for miniaturized high‐throughput cell assays and for label‐free molecular high‐content drug profiling, respectively. Here, nanoliter‐scale cell assays are integrated on DMAs with MALDI–MS imaging (MALDI–MSI) approaches to a droplet microarray–mass spectrometry imaging (DMA–MSI) platform. Using A549 lung cancer cells, concentration‐response profiling of a pharmaceutical compound, the fatty acid synthase inhibitor GSK2194069, are demonstrated. Direct cell culture on DMAs enables combination of microscopy and high speed, high molecular content analysis using MALDI–MSI. Miniaturization of array spots down to 0.5 mm confining 40 nL droplets allows for MALDI imaging analysis of as few as ten cells per spot. Partial automation ensures a fast sample preparation workflow. Taken together, the integrated DMA–MSI platform that combines MALDI‐MSI, as a label‐free analytical readout, with the miniaturized droplet microarray platform is a valuable complement to high throughput cell‐based assays technologies

Mathematical model of elastic ribbed shell dynamics interaction with viscous liquid under vibration

The mechanical model of the system, formed by two surfaces of the coaxial cylindrical shells interacting with viscous incompressible liquid between them under vibration, is considered. The outer shell is geometrically irregular, and inner one is an absolutely rigid cylinder. The mathematical model of this system, consisting of differential equations in partial derivatives for describing dynamics of viscous incompressible liquid and an elastic ribbed shell together with boundary conditions is constructed. The expressions for amplitude frequency characteristics of outer geometrically irregular shell are discovered

Mathematical modeling of hydroelastic walls oscillations of the channel on Winkler foundation under vibrations

The bending oscillations of a narrow slit channel walls with highly viscous liquid inside and put on a vibrating Winkler foundation are investigated. The channel walls bending oscillations laws are discovered on the basis of hydroelasticity problem solution, as well as pressure in the liquid ones. The deflections amplitudes distribution and liquid pressure along the channel functions are constructed. The obtained results allow investigating dynamic processes, conditioned by constructions elastic elements and viscous liquid interaction in lubrication system, damping and various devices and units

Droplet Microarray Based Screening Identifies Proteins for Maintaining Pluripotency of hiPSCs

Human induced pluripotent stem cells (hiPSCs) are crucial for disease modeling, drug discovery, and personalized medicine. Animal-derived materials hinderapplications of hiPSCs in medical fields. Thus, novel and well-defined substrate coatings capable of maintaining hiPSC pluripotency are important for advancing biomedical applications of hiPSCs. Here a miniaturized droplet microarray (DMA) platform to investigate 11 well-defined proteins, their 55 binary and 165 ternary combinations for their ability to maintainpluripotency of hiPSCs when applied as a surface coating, is used. Using this screening approach, ten protein group coatings are identified, which promote significantly higher NANOG expression of hiPSCs in comparison with Matrigel coating. With two of the identified coatings, long-term pluripotency maintenance of hiPSCs and subsequent differentiation into three germ layers are achieved. Compared with conventional high-throughput screening (HTS) in 96-well plates, the DMA platform uses only 83 µL of protein solution (0.83 µg total protein) and only ≈2.8 × 10$^5$ cells, decreasing the amount of proteins and cells ≈860 and 25-fold, respectively. The identified proteins will be essential for research and applications using hiPSCs, while the DMA platform demonstrates great potential for miniaturized HTS of scarce cells or expensive materials such as recombinant proteins

Influence of ultrafine particles on structure, mechanical properties, and strengthening of ductile cast iron

Integrated assessment of the influence of an ultrafine mixture TiO2 + ZrO2 + Na3AlF6 on the formation of the structure, mechanical properties, and strengthening of ductile cast iron was made in the paper. The structural-phase composition of ductile cast iron was studied by means of scanning electron microscopy and a transmission electron microscope. Plastic deformation was determined during testing of uniaxial compression. The change in the structural state of the alloy and in its mechanical properties was observed. Quantitative assessment of contributions of separate physical mechanisms to strengthening characteristics of unmodified and modified ductile cast iron was made