Knowledge of spatial chromosomal organizations is critical for the study of transcriptional regulation and other nuclear processes in the cell. Recently, chromosome conformation capture (3C) based technologies, such as Hi-C and TCC, have been developed to provide a genome-wide, three-dimensional (3D) view of chromatin organization. Appropriate methods for analyzing these data and fully characterizing the 3D chromosomal structure and its structural variations are still under development. Here we describe a novel Bayesian probabilistic approach, denoted as “Bayesian 3D constructor for Hi-C data” (BACH), to infer the consensus 3D chromosomal structure. In addition, we describe a variant algorithm BACH-MIX to study the structural variations of chromatin in a cell population. Applying BACH and BACH-MIX to a high resolution Hi-C dataset generated from mouse embryonic stem cells, we found that most local genomic regions exhibit homogeneous 3D chromosomal structures. We further constructed a model for the spatial arrangement of chromatin, which reveals structural properties associated with euchromatic and heterochromatic regions in the genome. We observed strong associations between structural properties and several genomic and epigenetic features of the chromosome. Using BACH-MIX, we further found that the structural variations of chromatin are correlated with these genomic and epigenetic features. Our results demonstrate that BACH and BACH-MIX have the potential to provide new insights into the chromosomal architecture of mammalian cells.

Biomarkers in sweat are a largely untapped source of health information. Most of the currently available sweat harvesting and testing devices are incapable of operating under low-sweat rates such as those experienced by humans at rest. Here we analyze the in vitro and in vivo sampling of sweat through osmosis via the use of a hydrogel interfaced with the skin, without need for active perspiration. The hydrogel also interfaces with paper-based microfluidics to transport the fluid via capillary forces toward a testing zone and then evaporation pad. We show that the hydrogel solute content and area of the evaporation pad regulate the long-term extraction of sweat and its associated biomarkers. The results indicate that the platform can sample biomarkers from a model skin system continuously for approximately 12 h. On-skin testing of the platform on both resting and exercising human subjects confirms that it can sample sweat lactate directly from the surface of skin. The results highlight that lactate in sweat increases with exercise and as a direct result of muscle activity. Implementation of such new principles for sweat fluid harvesting and management via wearable patch devices can contribute toward the advancement of next generation wearables.

Ubiquitous physiological monitoring will be a key driving force in the upcoming wireless health revolution. Cardiac and brain signals in the form of ECG and EEG are two critical health indicators that directly benefit from long-term monitoring. Despite advancements in wireless technology and electronics miniaturization, however, the use of wireless home ECG/EEG monitoring is still limited by the inconvenience and discomfort of wet adhesive electrodes.We have developed a wireless biopotential instrumentation system using non-contact capacitive electrodes that operate without skin contact. The sensors can be embedded within comfortable layers of fabric for unobtrusive use. All of the issues relating to the design of low noise, high performance capacitive sensors are discussed along with full technical details, circuit schematics and construction techniques.The non-contact electrode has been integrated into both a wearable ECG chest harness as well a EEG headband. We have also designed a compact, battery-powered, wireless data acquisition system to interface with multiple electrodes and monitor patient cardiac and neural signals in real time. Experimental data shows that the non-contact capacitive electrode perform comparable to Ag/AgCl electrodes using our special chest harness and head bands to ensure tight, movement-free electrode positioning.

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.

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