Applying causal discovery to single-cell analyses using CausalCell.

Correlation between objects is prone to occur coincidentally, and exploring correlation or association in most situations does not answer scientific questions rich in causality. Causal discovery (also called causal inference) infers causal interactions between objects from observational data. Reported causal discovery methods and single-cell datasets make applying causal discovery to single cells a promising direction. However, evaluating and choosing causal discovery methods and developing and performing proper workflow remain challenges. We report the workflow and platform CausalCell (http://www.gaemons.net/causalcell/causalDiscovery/) for performing single-cell causal discovery. The workflow/platform is developed upon benchmarking four kinds of causal discovery methods and is examined by analyzing multiple single-cell RNA-sequencing (scRNA-seq) datasets. Our results suggest that different situations need different methods and the constraint-based PC algorithm with kernel-based conditional independence tests work best in most situations. Related issues are discussed and tips for best practices are given. Inferred causal interactions in single cells provide valuable clues for investigating molecular interactions and gene regulations, identifying critical diagnostic and therapeutic targets, and designing experimental and clinical interventions.

Design of protective and high sensitivity encapsulation layers in wearable devices.

Elastomeric encapsulation layers are widely used in soft, wearable devices to physically isolate rigid electronic components from external environmental stimuli (e.g., stress) and facilitate device sterilization for reusability. In devices experiencing large deformations, the stress-isolation effect of the top encapsulation layer can eliminate the damage to the electronic components caused by external forces. However, for health monitoring and sensing applications, the strain-isolation effect of the bottom encapsulation layer can partially block the physiological signals of interest and degrade the measurement accuracy. Here, an analytic model is developed for the strain- and stress-isolation effects present in wearable devices with elastomeric encapsulation layers. The soft, elastomeric encapsulation layers and main electronic components layer are modeled as transversely isotropic-elastic mediums and the strain- and stress-isolation effects are described using isolation indexes. The analysis and results show that the isolation effects strongly depend on the thickness, density, and elastic modulus of both the elastomeric encapsulation layers and the main electronic component layer. These findings, combined with the flexible mechanics design strategies of wearable devices, provide new design guidelines for future wearable devices to protect them from external forces while capturing the relevant physiological signals underneath the skin. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11431-022-2034-y.

Moisture-resistant MXene-sodium alginate sponges with sustained superhydrophobicity for monitoring human activities.

Wearable mechanical sensors are easily influenced by moisture resulting in inaccuracy for monitoring human health and body motions. Though the superhydrophobic barrier has been extensively explored as passive water repel strategy on the sensor surface, the dense superhydrophobic surface not only limits the sensor working under large deformations but also inevitable degradation in high humidity or saturation water vapor environments. This work reports a superhydrophobic MXene-sodium alginate sponge (SMSS) pressure sensor with a low voltage Joule heating effect to provide sustain moisture-insensitive property for both sensing performance and superhydrophobicity by heating-driven water molecules away. Because of the positive temperature coefficient under pressure applied, the Joule heating can provides a stable temperature to the moisture-insensitivity property during the whole dynamic pressure cycled. Therefore, the pressure sensor with a simple spray-coating superhydrophobic coating on the outer layer demonstrates key capabilities even in extreme use scenarios with high humidity or water vapor and also provides stable and reliable bio-signal monitoring.

Strain-Tunable Microfluidic Devices with Crack and Wrinkle Microvalves for Microsphere Screening and Fluidic Logic Gates.

Mechanical instabilities in soft materials have led to the formation of unique surface patterns such as wrinkles and cracks for a wide range of applications that are related to surface morphologies and their dynamic tuning. Here, we report a simple yet effective strategy to fabricate strain-tunable crack and wrinkle microvalves with dimensions responding to the applied tensile strain. The crack microvalves initially closed before stretching are opened as the tensile strain is applied, whereas the wrinkle microvalves exhibit the opposite trend. Next, the performance of crack and wrinkle microvalves is characterized. The design predictions on the bursting pressure of microvalves and others from the theory agree reasonably well with the experimental measurements. The microfluidic devices with strain-tunable crack and wrinkle microvalves have then been demonstrated for microsphere screening and programmable microfluidic logic devices. The demonstrated microfluidic devices complement the prior studies to open up opportunities in microparticle/cell manipulations, fluidic operations, and biomedicine.

Skin-interfaced microfluidic devices with one-opening chambers and hydrophobic valves for sweat collection and analysis.

Soft, skin-interfaced microfluidic platforms are capable of capturing, storing, and assessing sweat chemistry and total sweat loss, which provides essential insight into human physiological health. However, sweat loss from the outlet of the microfluidic devices often leads to deviation of the measured concentration of the biomarker or electrolyte from the actual value. Here, we introduce hydrophobic valves at the junction of the chamber and the microfluidic channel as a new chamber design to reduce sweat evaporation. Because the advancing front of the liquid in the hydrophilic microchannel is blocked by the hydrophobic valve, the fluid flows into the chambers, forms the initial meniscus, and completely fills the chambers along the initial meniscus. Fluid dynamic modeling and numerical simulations provide critical insights into the sweat sampling mechanism into the chambers. With significantly reduced evaporation and contamination, the sweat sample can be easily stored for a long time for later analysis when in situ analysis is limited. Additionally, the design with multiple chambers can allow sequential generation of sweat collection at different times for long-term analysis. The in situ real-time measurements of the sweat loss and pH value analysis from the human subject demonstrate the practical utility of the devices in collecting, storing, and analyzing the sweat generated from sweat glands on the skin.