Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 μm wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

A Disposable DNA Analysis Chip with a Powerless Actuator

A non-instrumented, single-use, affordable, and fully- yet safely-disposable DNA analysis system for Point Of Care (POC) diagnostic process has been proposed by integrating (1) a hydration-reactive mixture for a portable heating element as a powerless actuator, (2) commercially available optical adhesive films as valves, and (3) an exothermic reaction-based recombinant polymerase amplification (RPA) process for non-instrumented DNA amplification. The operational error tolerance of the adhesive valves was evaluated by gas production and long-lasting ability, and the amplification performance of the RPA device was validated by gel electrophoresis. Finally, a DNA analysis device was fabricated and tested based on a hydration reaction with a DNA extraction microfluidic channel and an exothermic reaction-based RPA device. In the DNA extraction process, dimethyl adipimidate (DMA) solution was used to eliminate some required injection steps from the extraction process. The integrated system's functionality was successfully demonstrated, and the suggested system could become a foundation for the ultimate total solution for POC DNA analysis.

In-Situ Detection of Fluid Media Based on Three-Dimensional Dendritic Silver Surface-Enhanced Raman Scattering Substrate

In this paper, a highly active surface enhanced Raman scattering (SERS) substrate based on three-dimensional (3D) dendritic silver nanostructure was constructed in microfluidic channel by one-step electrodisplacement reaction for in-situ...

SERS Platform Based on Hollow-Core Microstructured Optical Fiber: Technology of UV-Mediated Gold Nanoparticle Growth

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for biosensing. However, SERS analysis has several concerns: the signal is limited by a number of molecules and the area of the plasmonic substrate in the laser hotspot, and quantitative analysis in a low-volume droplet is confusing due to the change of concentration during quick drying. The usage of hollow-core microstructured optical fibers (HC-MOFs) is thought to be an effective way to improve SERS sensitivity and limit of detection through the effective irradiation of a small sample volume filling the fiber capillaries. In this paper, we used layer-by-layer assembly as a simple method for the functionalization of fiber capillaries by gold nanoparticles (seeds) with a mean diameter of 8 nm followed by UV-induced chloroauric acid reduction. We also demonstrated a simple and quick technique used for the analysis of the SERS platform formation at every stage through the detection of spectral shifts in the optical transmission of HC-MOFs. The enhancement of the Raman signal of a model analyte Rhodamine 6G was obtained using such type of SERS platform. Thus, a combination of nanostructured gold coating as a SERS-active surface and a hollow-core fiber as a microfluidic channel and a waveguide is perspective for point-of-care medical diagnosis based on liquid biopsy and exhaled air analysis.

Multi-jet ice 3D printing

Purpose Multi-jet deposition of the materials is a matured technology used for graphic printing and 3 D printing for a wide range of materials. The multi-jet technology is fine-tuned for liquids with a specific range of viscosity and surface tension. However, the use of multi-jet for low viscosity fluids like water is not very popular. This paper aims to demonstrate the technique, particularly for the water-ice 3 D printing. 3 D printed ice parts can be used as patterns for investment casting, templates for microfluidic channel fabrication, support material for polymer 3 D printing, etc. Design/methodology/approach Multi-jet ice 3 D printing is a novel technique for producing ice parts by selective deposition and freezing water layers. The paper confers the design, embodiment and integration of various subsystems of multi-jet ice 3 D printer. The outcomes of the machine trials are reported as case studies with elaborate details. Findings The prismatic geometries are realized by ice 3 D printing. The accuracy of 0.1 mm is found in the build direction. The part height tends to increase due to volumetric expansion during the phase change. Originality/value The present paper gives a novel architecture of the ice 3 D printer that produces the ice parts with good accuracy. The potential applications of the process are deliberated in this paper.

Opto-Microfluidic Fabry-Perot Sensor with Extended Air Cavity and Enhanced Pressure Sensitivity

An opto-microfluidic static pressure sensor based on a fiber Fabry-Perot Interferometer (FPI) with extended air cavity for enhancing the measuring sensitivity is proposed. The FPI is constructed in a microfluidic channel by the combination of the fixed fiber-end reflection and floating liquid surface reflection faces. A change of the aquatic pressure will cause a drift of the liquid surface and the pressure can be measured by detecting the shift of the FPI spectrum. Sensitivity of the sensor structure can be enhanced significantly by extending the air region of the FPI. The structure is manufactured by using a common single-mode optical fiber, and a silica capillary with the inner wall coated with a hydrophobic film. A sample with 3500 μm air cavity length has demonstrated the pressure sensitivity of about 32.4 μm/kPa, and the temperature cross-sensitivity of about 0.33 kPa/K.

Hybrid-Integrated Biosensor for Express Determination of Protein Markers of Diseases based on Molecular Recognition and Direct Fluorimetric Detection

Ways of creating new generation biosensors for multiparametric express diagnostics based on molecular recognition and direct fluorimetric registration of a peptide aptamer — protein marker complex were considered. The biosensor platform comprises a microfluidic channel for delivery sample solutions, coupled with flow-through zones containing covalently attached arrays of peptide probes — aptamers. An outer glass window of the biochip assembly contains a layer of luminophore ZnS:Cu, bound on it via an acrylic lacquer and intended for the re-emitting native fluorescence of bound proteins into the longer wavelength range, more efficient in registering signals with CMOS sensors. The aptamers were designed using "Protein 3D" program for analysis of spatial complementarity of protein structures. The peptide, complementary to Troponin T, was modified by replacement of aromatic amino acid residue while maintaining the spatial configuration. The complementarity of peptide and Troponin T was confirmed using a capillary electrophoresis-on-a-chip. Biosensors are manufactured using thick-film technology and photolithography. The fluorescence of marker proteins was excited using UV-LED with a radiation wavelength of 275 nm. The limit of detection achieved for Troponin T was 6 ng/ml.

Flow Control in Passive 3D Paper-Based Microfluidic Pump by Variable Porosity

Active pumps are often used in microfluidic devices for programmable fluid flowrate in a microchannel. Active pumps have some drawbacks due to their large size and requirement of external power. To overcome them, a new class of passive pumps based on capillary action in cellulose material, known as paper-based microfluidic pumps, has recently been explored. In this study, fluid flow in 3D paper-based pumps was investigated using flowrate measurements in microchannels. In order to develop 3D cylindrical pumps, Whatman filter paper grade 1 was shredded, mixed with water, molded and dried. The patterned serpentine channel was created using a CO2 Laser Cutting/Engraving machine. The 3D paper-based pump was integrated with microfluidic channel. The effect of paper pumps of different porosities on the fluid flowrate through a serpentine microchannel was investigated. It was found that flowrate of the fluid flowing through the channel increases with an increase in the pump’s porosity. Moreover, these pumps have the ability to transport larger volumes of liquid with improved flowrate, programmability and control, in addition to being inexpensive and simple to design and fabricate. These 3D pumps will help researchers move closer to developing an effective miniaturized diagnostic platform for point-of-care (POC) diagnostic applications.

Osmotically Enabled Wearable Patch for Sweat Harvesting and Lactate Quantification

Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in humans at rest), and do not provide adequate information about the relationship between sweat and blood lactate levels. Here, we discuss the on-skin operation of our recently developed wearable sweat sampling patch. The patch combines osmosis (using hydrogel discs) and capillary action (using paper microfluidic channel) for long-term sweat withdrawal and management. When subjects are at rest, the hydrogel disc can withdraw fluid from the skin via osmosis and deliver it to the paper. The lactate amount in the fluid is determined using a colorimetric assay. During active sweating (e.g., exercise), the paper can harvest sweat even in the absence of the hydrogel patch. The captured fluid contains lactate, which we quantify using a colorimetric assay. The measurements show the that the total number of moles of lactate in sweat is correlated to sweat rate. Lactate concentrations in sweat and blood correlate well only during high-intensity exercise. Hence, sweat appears to be a suitable biofluid for lactate quantification. Overall, this wearable patch holds the potential of providing a comprehensive analysis of sweat lactate trends in the human body.

Filtration extraction method using microfluidic channel for measuring environmental DNA

The environmental DNA (eDNA) method, which is widely applied for biomonitoring, is limited to laboratory analysis and processing. In this study, we developed a filtration/extraction component using a microfluidic channel, Biryu-Chip (BC), and a filtration/extraction method, BC method, to minimize the volume of the sample necessary for DNA extraction and subsequent PCR amplification. We tested the performance of the BC method and compared it with the Sterivex filtration/extraction method using aquarium and river water samples. We observed that using the BC method, the same concentration of the extracted DNA was obtained with 1/20–1/40 of the filtration volume of the Sterivex method, suggesting that the BC method can be widely used for eDNA measurement. In addition, we could perform on-site measurements of eDNA within 30 min using a mobile PCR device. Using the BC method, filtration and extraction could be performed easily and quickly. The PCR results obtained by the BC method were similar to those obtained by the Sterivex method. The BC method required fewer steps and therefore, the risk of DNA contamination could be reduced. When combined with a mobile PCR, the BC method can be applied to easily detect eDNA within 30 min from a few 10 mL of the water sample, even on-site.