Recent advances in lab-on-a-chip technology establish solid foundations for wearable biosensors. These newly emerging wearable biosensors are capable of non-invasive, continuous monitoring by miniaturization of electronics and integration with microfluidics. The advent of flexible electronics, biochemical sensors, soft microfluidics, and pain-free microneedles have created new generations of wearable biosensors that explore brand-new avenues to interface with the human epidermis for monitoring physiological status. However, these devices are relatively underexplored for sports monitoring and analytics, which may be largely facilitated by the recent emergence of wearable biosensors characterized by real-time, non-invasive, and non-irritating sensing capacities. Here, we present a systematic review of wearable biosensing technologies with a focus on materials and fabrication strategies, sampling modalities, sensing modalities, as well as key analytes and wearable biosensing platforms for healthcare and sports monitoring with an emphasis on sweat and interstitial fluid biosensing. This review concludes with a summary of unresolved challenges and opportunities for future researchers interested in these technologies. With an in-depth understanding of the state-of-the-art wearable biosensing technologies, wearable biosensors for sports analytics would have a significant impact on the rapidly growing field—microfluidics for biosensing.
3D rotation is one of many fundamental manipulations to cells and imperative in a wide range of applications in single cell analysis involving biology, chemistry, physics and medicine. In this article, we report a dielectrophoresis-based, on-chip manipulation method that can load and rotate a single cell for 3D cell imaging and multiple biophysical property measurements. To achieve this, we trapped a single cell in constriction and subsequently released it to a rotation chamber formed by four sidewall electrodes and one transparent bottom electrode. In the rotation chamber, rotating electric fields were generated by applying appropriate AC signals to the electrodes for driving the single cell to rotate in 3D under control. The rotation spectrum for in-plane rotation was used to extract the cellular dielectric properties based on a spherical single-shell model, and the stacked images of out-of-plane cell rotation were used to reconstruct the 3D cell morphology to determine its geometric parameters. We have tested the capabilities of our method by rotating four representative mammalian cells including HeLa, C3H10, B lymphocyte, and HepaRG. Using our device, we quantified the area-specific membrane capacitance and cytoplasm conductivity for the four cells, and revealed the subtle difference of geometric parameters (i.e., surface area, volume, and roughness) by 3D cell imaging of cancer cells and normal leukocytes. Combining microfluidics, dielectrophoresis, and microscopic imaging techniques, our electrorotation-on-chip (EOC) technique is a versatile method for manipulating single cells under investigation and measuring their multiple biophysical properties.
Single-cell impedance flow cytometry (IFC) is emerging as a label-free and non-invasive method for characterizing the electrical properties and revealing sample heterogeneity. At present, most IFC studies utilize phenomenological parameters (e.g., impedance amplitude, phase and opacity) to characterize single cells instead of intrinsic biophysical metrics (e.g., radius r, cytoplasm conductivity σi and specific membrane capacitance Csm). Intrinsic parameters are normally calculated off-line by time-consuming model-fitting methods. Here, we propose to employ neural network (NN)-enhanced IFC to achieve both real-time single-cell intrinsic characterization and intrinsic parameter-based cell classification at high throughput. Three intrinsic parameters (r, σi and Csm) can be obtained online and in real-time via a trained NN at 0.3 ms per single-cell event, achieving significant improvement in calculation speed. Experiments involving four cancer cells and one lymphocyte cell demonstrated 91.5% classification accuracy in the cell type for a test group of 9751 cell samples. By performing a viability assay, we provide evidence that the IFC test per se would not substantially affect the cell property. We envision that the NN-enhanced real-time IFC will provide a new platform for high-throughput, real-time and online cell intrinsic electrical characterization.
Cells have different intrinsic markers such as mechanical and electrical properties, which may be used as specific characteristics. Here, we present a microfluidic chip configured with two opposing optical fibers and four 3D electrodes for multiphysical parameter measurement. The chip leverages optical fibers to capture and stretch a single cell and uses 3D electrodes to achieve rotation of the single cell. According to the stretching deformation and rotation spectrum, the mechanical and dielectric properties can be extracted. We provided proof of concept by testing five types of cells (HeLa, A549, HepaRG, MCF7 and MCF10A) and determined five biophysical parameters, namely, shear modulus, steady-state viscosity, and relaxation time from the stretching deformation and area-specific membrane capacitance and cytoplasm conductivity from the rotation spectra. We showed the potential of the chip in cancer research by observing subtle changes in the cellular properties of transforming growth factor beta 1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) A549 cells. The new chip provides a microfluidic platform capable of multiparameter characterization of single cells, which can play an important role in the field of single-cell research.
1 April 2020 in Computer Methods and Programs in Biomedicine