Alcohol exposure has been postulated to adversely affect the physiology and function of the red blood cells (RBCs). The global pervasiveness of alcohol abuse, causing health issues and social problems, makes it imperative to resolve the physiological effects of alcohol on RBC physiology. Alcohol consumed recreationally or otherwise almost immediately alters cell physiology in ways that is subtle and still unresolved. In this paper, we introduce a high-resolution device for quantitative electrofluidic measurement of changes in RBC volume upon alcohol exposure. We present an exhaustive calibration of our device using model cells to measure and resolve volume changes down to 0.6 fL. We find an RBC shrinkage of 5.3% at 0.125% ethanol (the legal limit in the United States) and a shrinkage of 18.5% at 0.5% ethanol (the lethal limit) exposure. Further, we also measure the time dependence of cell volume shrinkage (upon alcohol exposure) and then recovery (upon alcohol removal) to quantify shrinkage and recovery of RBC volumes. This work presents the first direct quantification of temporal and concentration-dependent changes in red blood cell volume upon ethanol exposure. Our device presents a universally applicable highresolution and high-throughput platform to measure changes in cell physiology under native and diseased conditions. KEYWORDS: size of red blood cells, alcohol-induced shrinkage of biological cells, resistive pulse technique, micropores, electrofluidic devices ■ SIGNIFICANCE STATEMENTThe physiological changes in red blood cells caused by alcohol are not well understood, specifically the changes in cell volume that directly affect the oxygen carrying function of RBCs. Most of these changes are subtle and difficult to quantify. In the last decade, multiple methods have been used to measure this subtle change in cell size caused by alcohol exposure. The focus of this work is an electrofluidic sensing approach that accurately measures changes in cell volume of a cell population at single-cell resolution. The approach has potential to rapidly provide changes in cell volumes in cases like chemical exposure, malaria infection, large population sickle-cell disease screening, and quantifying cell lysis in a label-free, low-cost, and microscopy-independent way.
Recently there is a lot of attention given to manipulation of heat by constructing thermal devices such as thermal diodes, transistors and logic gates. Many of the models proposed have an asymmetry which leads to the desired effect. Presence of non-linear interactions among the particles is also essential. But, such models lack analytical understanding. Here we propose a simple, analytically solvable model of a thermal diode. Our model consists of classical spins in contact with multiple heat baths and constant external magnetic fields. Interestingly the magnetic field is the only parameter required to get the effect of heat rectification.
Physical parameters of the pathogenic cells, like its volume, shape, and stiffness, are important biomarkers for diseases, chemical changes within the cell, and overall cell health. The response of pathogenic bacteria and viruses to different chemical disinfectants is studied widely. Some of the routinely employed techniques to measure these changes require elaborate and expensive equipment which limits any study to a non-mobile research lab facility. Recently, we showed a micropore-based electro-fluidic technique to have great promise in measuring subtle changes in cell volumes at high throughput and resolution. This method, however, requires commercial amplifiers, which makes this technique expensive and incompatible for in-field use. In this paper, we develop a home-built amplifier to make this technique in-field compatible and apply it to measure changes in bacterial volumes upon exposure to alcohol. First, we introduce our low-cost and portable transimpedance amplifier and characterize the maximum range, absolute error percentage, and RMS noise of the amplifier in the measured current signal, along with the amplifier’s bandwidth, and compared these characteristics with the commercial amplifiers. Using our home-built amplifier, we demonstrate a high throughput detection of ~1300 cells/second and resolve cell diameter changes down to 1 μm. Finally, we demonstrate measurement of cell volume changes in E. coli bacteria when exposed to ethanol (5% v/v), which is otherwise difficult to measure via imaging techniques. Our low-cost amplifier (~100-fold lower than commercial alternatives) is battery-run, completely portable for point-of-care applications, and the electro-fluidic devices are currently being tested for in-field applications.
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