The sensitive detection of single-cell secreted lactic acid for glycolytic inhibitor screening with a microdroplet biosensor.

Lactic acid (LA) plays an important role in the tumor metabolism and malignant progression of various cancers. Herein, we have developed a one-step, wash-free microfluidic approach with droplet biosensors for the sensitive detection of LA secreted by a single tumor cell. Our assay integrates the enzyme-assisted chemical conversion of LA in small-volume (4.2 nL) droplets for fluorescence signal readout. The microdroplet assay achieved a limit of detection of 1.02 µM and was more sensitive than the commercial ELISA kit by nearly two orders of magnitude. A good specificity has been demonstrated for this assay by testing various ions and biomolecules from the culture medium. This droplet assay allows us to acquire the profiles of the lactic acid secretion of tumor cells under the influence of glycolytic inhibitors at the single-cell level. It offers a useful research tool to study the cell-to-cell differences of LA secretion and glycolytic inhibitor screening for cancer research.

Highly Stretchable and Sensitive Pressure Sensor Array Based on Icicle-Shaped Liquid Metal Film Electrodes.

Flexible pressure sensors emerge for important applications in wearable electronics, with increasing requirements for high sensitivity, fast response, and low detection limit. However, there is still a challenge in this field, that is, how to maximize both the electrical performance and mechanical stretchability simultaneously. Here, we report a straightforward and cost-effective method to fabricate highly stretchable and sensitive capacitive pressure sensor arrays. It features a unique design of integrating the icicle-shaped liquid metal film electrode and reliable processing of the liquid metal and elastomer. Under an external load, the deformation of the elastic bump structure dramatically results in an increase in the overlapping area of the electrodes and a decrease in the separation distance, offering a new capacitive sensing scheme with an enhanced sensitivity. Our sensor has been demonstrated with a high sensitivity of 39% kPa-1 in the range of 0-1 kPa, limit of detection as low as 12 Pa, hysteresis error of 8.46% at a maximum pressure of 25 kPa, and stretchability up to 94% strain without any failure. The arrayed sensor has been successfully applied to force measurements on a curved surface, contour mapping of external loads, and monitoring of contact pressures under various cervical postures.

Advancing single-cell proteomics and metabolomics with microfluidic technologies.

Recent advances in single-cell analysis have unraveled substantial heterogeneity among seemingly identical cells at genomic and transcriptomic levels. These discoveries have urged scientists to develop new tools that are capable of investigating single cells from a broader set of "omics". Proteomics and metabolomics, for instance, are of particular interest as they are closely correlated with a dynamic picture of cellular behaviors and phenotypic identities. The development of such tools requires highly efficient isolation and processing of a large number of individual cells, where techniques such as microfluidics are extremely useful. Here, we review the recent advances in single-cell proteomics and metabolomics, with a focus on microfluidics-based platforms. We highlight a vast array of emerging microfluidic formats for single-cell isolation and manipulation, and how the state-of-the-art analytical tools are coupled with such platforms for proteomic and metabolomic profiling.

Sensitive Detection of Single-Cell Secreted H2O2 by Integrating a Microfluidic Droplet Sensor and Au Nanoclusters.

As an important signaling molecule, hydrogen peroxide (H2O2) secreted externally by the cells influences cell migration, immunity generation, and cellular communications. Herein, we have developed a microfluidic approach with droplets in combination with Au nanoclusters for the sensitive detection of H2O2 secreted by a single cell. Isolated in the ultrasmall volume (4.2 nL) of a microdroplet, single-cell secreted H2O2 can initiate dramatic fluorescence changes of horseradish peroxidase-Au nanoclusters. We have demonstrated an ultrahigh sensitivity (200-400 attomole H2O2 directly measured from a single cell) with good specificity. It offers a useful research tool to study the cell-to-cell differences of H2O2 secretion at the single-cell level.

A Comprehensive Prediction Model of Hydraulic Extended-Reach Limit Considering the Allowable Range of Drilling Fluid Flow Rate in Horizontal Drilling.

Hydraulic extended-reach limit (HERL) model of horizontal extended-reach well (ERW) can predict the maximum measured depth (MMD) of the horizontal ERW. The HERL refers to the well's MMD when drilling fluid cannot be normally circulated by drilling pump. Previous model analyzed the following two constraint conditions, drilling pump rated pressure and rated power. However, effects of the allowable range of drilling fluid flow rate (Q min ≤ Q ≤ Q max ) were not considered. In this study, three cases of HERL model are proposed according to the relationship between allowable range of drilling fluid flow rate and rated flow rate of drilling pump (Q r ). A horizontal ERW is analyzed to predict its HERL, especially its horizontal-section limit (L h ). Results show that when Q min ≤ Q r ≤ Q max (Case I), L h depends both on horizontal-section limit based on rated pump pressure (L h1 ) and horizontal-section limit based on rated pump power (L h2 ); when Q min < Q max < Q r (Case II), L h is exclusively controlled by L h1 ; while L h is only determined by L h2 when Q r < Q min < Q max (Case III). Furthermore, L h1 first increases and then decreases with the increase in drilling fluid flow rate, while L h2 keeps decreasing as the drilling fluid flow rate increases. The comprehensive model provides a more accurate prediction on HERL.