Impedance‐Enabled Camera‐Free Intrinsic Mechanical Cytometry

Abstract

and isotopes), requiring tedious sample preparation, invasive operation, and prior knowledge of cell specificity. [3] In contrast, biophysical methods measure the mechanical, electrical, and optical properties to perform quick, label-free, and non-invasive single-cell characterization, [4] so as to facilitate subsequent operations on cells such as sorting, [5] culturing, [6] and omics analysis. [7] Cellular biophysical properties have been proven as effective biomarkers for diagnosing diseases and widely used in cell biology, dynamics, and pathology research. [8] As one of the biophysical properties, mechanical properties of cells reflect the characteristics of cell membranes, and cytoskeletal networks, which influence cellular and subcellular functions, [9] including cell adhesion, migration, polarization, and differentiation, as well as organelle organization and trafficking inside the cytoplasm. [10] At present, there are many classic methods for characterizing the mechanical properties of single cells, such as atomic force microscopy (AFM), micropipette aspiration, parallel-plate rheometry, and optical stretching. [11] These methods evaluate time-resolved cellular responses to external stresses, and offer effective means to obtain the single-cell intrinsic mechanical properties (e.g., Young's modulus and viscosity). However, they suffer from inherent problems with technically demanding and time-consuming procedures, which lead to difficulty in operation and low throughput (<1 cell min −1 ). [11] As an attractive alternative, microfluidics approaches allow detecting cell deformability at high throughput but low complexity for single-cell analysis. [12] However, the characterization relies on expensive and complex high-speed imaging systems with time-consuming image processing algorithms to obtain the dynamic deformation process of the cells, which limits the real-time capability desired for downstream cell manipulation and analysis such as deformability-based sorting.Exploiting electronic means or impedance cytometry for cellular mechanical characterization presents a new alternative approach. [13] Based on direct-current (DC) Coulter-counter, the visco-node-pore sensing system [14] is proposed to characterize the cellular mechanics solely by the current signal. It employs elegant design of straight [14] or sinusoidal [15] constriction channels to correlate the current signal to the mechanical viscoelastic properties, and is applied in biological applications. [16] But the footprint for the series of node-pore structure may limit Mechanical properties of single cells are important label-free biomarkers normally measured by expensive and complex imaging systems. To unlock this limit and allow mechanical properties comparable across different measurement platforms, camera-free intrinsic mechanical cytometry (CFIMC) is proposed for on-the-fly measurement of two major intrinsic mechanical parameters, that is, Young's modulus E and fluidity β, of single cells. CFIMC adopts a framework that couples the impedance ele...

Label-free microfluidic cell sorting and detection for rapid blood analysis

“…177 After calibration with agarose gel particles, a power-law rheology (PLR) model was used to represent cell creeping in the constriction channel to extract quantitative information on cell elasticity and fluidity of leukaemia cells (HL-60). To avoid the use of expensive high-speed cameras, researchers have developed impedance-based detection methods to profile cell biophysical properties by quantifying the cell geometrical change, 178 or cell creeping process 179 in an optics-free and label-free manner. A recent study was reported by Petchakup et al who defined a novel "electrical deformability index" for single cell electro-mechano-phenotyping (Fig.…”

Performance-enhanced clogging-free viscous sheath constriction impedance flow cytometry

“…[12][13][14][15][16][17][18] So far, IFC techniques have made progress in high-content measurement of single-cell biophysical multi-modal fingerprints including cell size, 19 shape, 20 and electrical [21][22][23] and mechanical properties. 24,25 Most of the IFC techniques use a narrow channel [26][27][28][29][30][31][32][33] as mechanical constriction (MC) to decrease the sensing aperture (SA), which matches the cell size to achieve high detection sensitivity. Frequently, MC refers to impedance cytometers housing a "constriction channel", whose dimensions are smaller than that of the cells under investigation, so that a mechanical deformation of the cells is induced.…”

Magnetically Actuated Hydrogel Stamping-Assisted Cellular Mechanical Analyzer for Stored Blood Quality Detection

“…Cellular mechanical properties are closely associated with cell status and disease, including cellular senescence, cellular storage lesions, sickle cell, and sepsis, as they reflect the internal structure changes of cells. − Thus, biomechanical analysis is promising to identify cell states, , diagnose cancer, detect rare cells, etc. , For instance, the stiffness of red blood cells (RBCs) gradually increases in the cryogenic storage environment of blood banks as the duration of storage lengthens, so monitoring the cellular mechanical properties is essential for prescreening of blood to reduce the risk of transfusion. , …”