A handheld plug-and-play microfluidic liquid handling automation platform for immunoassays.

Lab-on-a-chip technologies and microfluidics have pushed miniaturized liquid handling to unprecedented precision, integration, and automation, which improved the reaction efficiency of immunoassays. However, most microfluidic immunoassay systems still require bulky infrastructures, such as external pressure sources, pneumatic systems, and complex manual tubing and interface connections. Such requirements prevent plug-and-play operation at the point-of-care (POC) settings. Here we present a fully automated handheld general microfluidic liquid handling automation platform with a plug-and-play 'clamshell-style' cartridge socket, a miniature electro-pneumatic controller, and injection-moldable plastic cartridges. The system achieved multi-reagent switching, metering, and timing control on the valveless cartridge using electro-pneumatic pressure control. As a demonstration, a SARS-CoV-2 spike antibody sandwich fluorescent immunoassay (FIA) liquid handling was performed on an acrylic cartridge without human intervention after sample introduction. A fluorescence microscope was used to analyze the result. The assay showed a limit of detection at 31.1 ng/mL, comparable to some previously reported enzyme-linked immunosorbent assays (ELISA). In addition to automated liquid handling on the cartridge, the system can operate as a 6-port pressure source for external microfluidic chips. A rechargeable battery with a 12 V 3000 mAh capacity can power the system for 42 h. The footprint of the system is 16.5 × 10.5 × 7 cm, and the weight is 801 g, including the battery. The system can find many other POC and research applications requiring complex liquid manipulation, such as molecular diagnostics, cell analysis, and on-demand biomanufacturing.

A large-scale brain network of species-specific dynamic human body perception.

This ultrahigh field 7 T fMRI study addressed the question of whether there exists a core network of brain areas at the service of different aspects of body perception. Participants viewed naturalistic videos of monkey and human faces, bodies, and objects along with mosaic-scrambled videos for control of low-level features. Independent component analysis (ICA) based network analysis was conducted to find body and species modulations at both the voxel and the network levels. Among the body areas, the highest species selectivity was found in the middle frontal gyrus and amygdala. Two large-scale networks were highly selective to bodies, dominated by the lateral occipital cortex and right superior temporal sulcus (STS) respectively. The right STS network showed high species selectivity, and its significant human body-induced node connectivity was focused around the extrastriate body area (EBA), STS, temporoparietal junction (TPJ), premotor cortex, and inferior frontal gyrus (IFG). The human body-specific network discovered here may serve as a brain-wide internal model of the human body serving as an entry point for a variety of processes relying on body descriptions as part of their more specific categorization, action, or expression recognition functions.

Personal NO2 sensor demonstrates feasibility of in-home exposure measurements for pediatric asthma research and management.

BACKGROUND: One of the most common pollutants in residences due to gas appliances, NO2 has been shown to increase the risk of asthma attacks after small increases in short term exposure. However, standard environmental sampling methods taken at the regional level overlook chronic intermittent exposure due to lack of temporal and spatial granularity. Further, the EPA and WHO do not currently provide exposure recommendations to at-risk populations. AIMS: A pilot study with pediatric asthma patients was conducted to investigate potential deployment challenges as well as benefits of home-based NO2 sensors and, when combined with a subject's hospital records and self-reported symptoms, the richness of data available for larger-scale epidemiological studies. METHODS: We developed a compact personal NO2 sensor with one minute temporal resolution and sensitivity down to 15 ppb to monitor exposure levels in the home. Patient hospital records were collected along with self-reported symptom diaries, and two example hypotheses were created to further demonstrate how data of this detail may enable study of the impact of NO2 in this sensitive population. RESULTS: 17 patients (55%) had at least 1 h each day with average NO2 exposure >21 ppb. Frequency of acute NO2 exposure >21 ppb was higher in the group with gas stoves (U = 27, p ≤ 0.001), and showed a positive correlation (rs = 0.662, p = 0.037, 95% CI 0.36-0.84) with hospital admissions. SIGNIFICANCE: Similar studies are needed to evaluate the true impact of NO2 in the home environment on at-risk populations, and to provide further data to regulatory bodies when developing updated recommendations.

A Discreet Wearable IoT Sensor for Continuous Transdermal Alcohol Monitoring - Challenges and Opportunities.

Non-invasive continuous alcohol (ethanol) monitoring has potential applications in both population research and in clinical management of acute alcohol intoxication or chronic alcoholism. Current wearable monitors based on transdermal alcohol content (TAC) sensing have limited accessibility and blood alcohol content (BAC) quantification accuracy. Here we describe the development of a self-contained discreet wearable transdermal alcohol (TAC) sensor in the form of a wristband or armband. This sensor can detect vapor-phase alcohol in perspiration from 0.09 ppm (equivalent to 0.09 mg/dL sweat alcohol concentration at 25 °C under Henry's Law equilibrium) to over 500 ppm at one-minute time resolution. Additionally, a digital sensor was employed to monitor the temperature and humidity levels inside the sensing chamber. Two male human subjects were recruited to conduct studies with alcohol consumption using calibrated prototype TAC sensors to validate the performance. Our preliminary data demonstrated that, under well-controlled conditions, this sensor can acquire TAC curves at low doses (1-2 standard drinks). Moreover, TAC data for different doses can be easily distinguished. However, substantial interpersonal and intrapersonal variabilities in measurement data were also observed in experiments with less controlled conditions. Our observations suggest that perspiration rate might be an important contributing factor to these variabilities. Further studies with sufficient sample sizes are required to validate and characterize the impact of different perspiration rates on TAC sensors, which may inform more reproducible and accurate sensor designs in the future.

Automaticity in processing spatial-numerical associations: Evidence from a perceptual orientation judgment task of Arabic digits in frames.

Human adults are faster to respond to small/large numerals with their left/right hand when they judge the parity of numerals, which is known as the SNARC (spatial-numerical association of response codes) effect. It has been proposed that the size of the SNARC effect depends on response latencies. The current study introduced a perceptual orientation task, where participants were asked to judge the orientation of a digit or a frame surrounding the digit. The present study first confirmed the SNARC effect with native Chinese speakers (Experiment 1) using a parity task, and then examined whether the emergence and size of the SNARC effect depended on the response latencies (Experiments 2, 3, and 4) using a perceptual orientation judgment task. Our results suggested that (a) the automatic processing of response-related numerical-spatial information occurred with Chinese-speaking participants in the parity task; (b) the SNARC effect was also found when the task did not require semantic access; and (c) the size of the effect depended on the processing speed of the task-relevant dimension. Finally, we proposed an underlying mechanism to explain the SNARC effect in the perceptual orientation judgment task.

A Cloud-connected NO2 and Ozone Sensor System for Personalized Pediatric Asthma Research and Management.

This paper presents a cloud-connected indoor air quality sensor system that can be deployed to patients' homes to study personal microenvironmental exposure for asthma research and management. The system consists of multiple compact sensor units that can measure residential NO2, ozone, humidity, and temperature at one-minute resolution and a cloud-based informatic system that acquires, stores, and visualizes the microenvironmental data in real-time. The sensor hardware can measure NO2 as low as 10 ppb and ozone at 15 ppb. The cloud informatic system is implemented using open-source software on Amazon Web Service for easy deployment and scalability. This system was successfully deployed to pediatric asthma patients' homes in a pilot study. In this study, we discovered that some families had short-term NO2 exposure higher than EPA's one-hour exposure limit (100 ppb), and NO2 micro-pollution episodes often arise from natural gas appliance usage such as gas stove burning during cooking. By combining the personalized air pollutant exposure measurements with the physiological responses from monitoring devices, patient diaries, or medical records, this system can potentially enable novel asthma research and personalized asthma management.

Multiparametric slice culture platform for the investigation of human cardiac tissue physiology.

Human cardiac slices have emerged as a promising model of the human heart for scientific research and drug testing. Retaining the normal tissue architecture, a multi-cell type environment, and the native extracellular matrix, human cardiac slices faithfully replicate organ-level adult cardiac physiology. Previously, we demonstrated that human cardiac tissue slices cultured for 24 h maintained normal electrophysiology. In this project, we further optimized the organotypic culture condition to maintain normal electrophysiology of the human cardiac slices for 4 days. The prolonged culture of human cardiac tissue slices demonstrated here enables the study of chronic drug effects, gene therapies, and gene editing. To achieve greater control of the culture environment, we have also developed an automated, self-contained heart-on-a-chip system. The culture system supports media circulation, oxygenation, temperature control, electrical stimulation, and static mechanical loading. The culture parameters can be individually adjusted to establish the optimal culture condition to achieve long-term culture and to minimize tissue dedifferentiation. The development of the heart-on-a-chip technology presented here further encourages the use of organotypic human cardiac slices as a platform for pre-clinical drug testing and research in human cardiac physiology.

A Wearable IoT Aldehyde Sensor for Pediatric Asthma Research and Management.

A cloud-based wearable IoT aldehyde sensor system for asthma research and management.

Does the spatial-numerical association of response codes effect depend on digits' relative or absolute magnitude? Evidence from a perceptual orientation judgment task.

Many previous studies have demonstrated the SNARC effect-i.e., participants are faster to respond with their left/right hand to small/large numbers. However, there is a debate on whether it is based on working or long-term memory (i.e., relative or absolute magnitude). Here, we examined the flexibility of the spatial-numerical associations using orientation judgment tasks. Participants were asked to judge the orientation of a rotated frame surrounding an Arabic digit under numerical ranges 1-6, 4-9 (Experiment 1), and 1-9 (Experiment 2). The task difficulty was manipulated by rotating stimuli. We observed a significant SNARC effect for range 1-6 and a reversed SNARC effect for 4-9, regardless of the total numerical range presented in the task. Furthermore, the SNARC effect became more salient with increasing task difficulty. Our results suggest that the SNARC effect is based on the absolute magnitude of digits, supporting the long-term memory explanation.

Spatial Representation of Ordinal Information.

Right hand responds faster than left hand when shown larger numbers and vice-versa when shown smaller numbers (the SNARC effect). Accumulating evidence suggests that the SNARC effect may not be exclusive for numbers and can be extended to other ordinal sequences (e.g., months or letters in the alphabet) as well. In this study, we tested the SNARC effect with a non-numerically ordered sequence: the Chinese notations for the color spectrum (Red, Orange, Yellow, Green, Blue, Indigo, and Violet). Chinese color word sequence reserves relatively weak ordinal information, because each element color in the sequence normally appears in non-sequential contexts, making it ideal to test the spatial organization of sequential information that was stored in the long-term memory. This study found a reliable SNARC-like effect for Chinese color words (deciding whether the presented color word was before or after the reference color word "green"), suggesting that, without access to any quantitative information or exposure to any previous training, ordinal representation can still activate a sense of space. The results support that weak ordinal information without quantitative magnitude encoded in the long-term memory can activate spatial representation in a comparison task.

A smartphone controlled handheld microfluidic liquid handling system.

Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.