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23 result(s) for "Gray, Bonnie L."
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A Single-Cell Optically Pumped Intrinsic Gradiometer
Optically pumped magnetometers (OPMs) provide a non-cryogenic alternative to superconducting quantum interference devices (SQUIDs) for detecting weak biomagnetic fields. We report the design, construction, and characterization of a single-cell intrinsic OPM gradiometer. The gradiometer employs a rubidium-87 vapor cell in an orthogonal pump and probe beam configuration. The pump beam was split to illuminate two parallel sensing regions of the cell, separated by a baseline of 3 cm, with opposing circular polarization. A linearly polarized probe beam propagated through both regions and was captured by a balanced polarimeter whose output directly measured the spatial magnetic gradient. This prototype achieved a common-mode rejection ratio exceeding 50 dB and a sensitivity of 267 pT/cm/√Hz without passive magnetic shielding, using active ambient-field coils. As a proof of concept, we recorded preliminary cardiac-synchronous magnetic measurements using an optical pulse sensor for beat segmentation. After bandpass filtering and ensemble averaging, a cardiac-synchronous waveform was observed, consistent with cardiac timing. Unlike many multi-cell gradiometers that require complex calibration, modulation, and passive shielding, this single-cell design reduces cost and complexity.
Potentiometric pH Sensor Based on Flexible Screen-Printable Polyaniline Composite for Textile-Based Microfluidic Applications
Skin pH can be used for monitoring infections in a healing wound, the onset of dermatitis, and hydration in sports medicine, but many challenges exist in integrating conventional sensing materials into wearable platforms. We present the development of a flexible, textile-based, screen-printed electrode system for biosensing applications, and demonstrate flexible polyaniline (PANI) composite-based potentiometric sensors on a textile substrate for real-time pH measurement. The pH response of the optimized PANI/dodecylbenzene sulfonic acid/screen-printing ink composite is compared to electropolymerized and drop-cast PANI sensors via open circuit potential measurements. High sensitivity was observed for all sensors between pH 3–10, with a composite based on PANI emeraldine base, demonstrating sufficient response time and a linear sensitivity of −27.9 mV/pH. This exceeded prior flexible screen-printed pH sensors in which all parts of the sensor, including the pH sensing material, are screen-printed. Even better sensitivity was observed for a PANI emeraldine salt composite (−42.6 mV/pH), although the response was less linear. Furthermore, the sensor was integrated into a screen-printed microfluidic channel demonstrating sample isolation during measurement for wearable, micro cloth-based analytical devices. This is the first fully screen-printed flexible PANI composite pH sensor demonstrated on a textile substrate that can additionally be integrated with textile-based microfluidic channels.
Microchannel Platform for the Study of Endothelial Cell Shape and Function
Microfabrication technology is implemented to realize a versatile platform for the study of endothelial cell (EC) shape and function. The platform contains arrays of microchannels, 25-225 [mu]m wide, that are fabricated by deep reactive ion etching (DRIE) of silicon and anodic bonding to glass and within which ECs are cultured. Silicon fluidic port modules, fabricated using a combination of silicon fusion bonding and anisotropic etching in KOH, provide a simple and reversible means of coupling, via standard tubing, between an individual microchannel and off-platform devices for flow monitoring and control. For flow experiments where a well-defined flow field is required, the channels are capped with either a glass lid or a thin, self-sealing elastomer membrane that can be punctured to provide direct access to cells within the microchannels. Under static culture conditions, bovine aortic ECs (BAECs) become progressively more elongated as the channel width decreases. The shape index, a dimensionless measure of cell roundness, decreases from 0.75+ or -0.01 (mean+ or -SEM) for BAECs cultured in 225 [mu]m-wide microchannels to 0.31+ or -0.02 in 25 [mu]m-wide channels. When cuboidal BAECs are grown in 200 [mu]m-wide microchannels and then subjected to a fluid shear stress of approximately 20 dyne/cm^2 (2 Pa), they progressively elongate and align in the direction of flow in a similar manner to cells cultured on plain surfaces. To demonstrate the utility of the microfabricated platform for studying aspects of EC function, whole-cell patch-clamp recordings were performed under static conditions in open microchannels. The platform is demonstrated to be a versatile tool for studying relationships between EC shape and function and for probing the effect of flow on ECs of different shapes. Specific future applications and extensions of platform function are discussed.
On-Board Array for Multiplexed Semi-Active Cooling-Rate-Controlled Cryopreservation of Living Cells
An optimal cooling rate is a critical factor affecting the survival of biological cells during cryopreservation. In this paper, a system for on-board cooling-rate-controlled cryopreservation under low-temperature (-80 °C) environments is developed with disposable, biocompatible polydimethylsiloxane (PDMS) storage chambers on top of localized heaters on printed circuit boards. The assembly allows the storage chambers to be removed from the temperature-controlled board and transferred from a −80 °C freezer to a liquid nitrogen tank for long-term cryopreservation. The use of PDMS enables the insertion of a syringe needle for loading samples, and during freezing, seeding extracellular ice formation. The PDMS storage chambers were fabricated using a polymethyl methacrylate mold made using a laser cutting machine. For each device, a copper thin film was deposited on a fiberglass epoxy substrate using electroless plating, and patterned using photolithography techniques into a micro-serpentine shape. The copper film functioned simultaneously as a resistive heating element and a temperature sensor with a proportional-integral-derivative feedback control program embedded in a microcontroller to semi-actively control the transient temperature profiles during the freezing process for multiple samples with different cooling rate requirements. The results show that the proposed devices are able to maintain a stable cooling rate down to 1 °C/min, which covers the optimal range for some mammalian cell types with low cell membrane permeability, for which low cooling rates are required. A heat transfer simulation was established to model transient and spatial temperature profiles of the device during freezing. Preliminary biological tests on yeast cells and their survival rates after on-board cryopreservation suggest that the prototype device can be a low-cost, reliable, and convenient tool for laboratory use in cryopreservation.
Fluidic Interconnects for Microfluidics: Chip to Chip and World to Chip
From the miniaturization of laboratory instrumentation for bedside rapid diagnosis of diseases to bioanalytical instrumentation for study of individual cells or molecules in new ways using micromachined structures, microfluidics is well established as an exciting new area of research with great promise and an ever-growing application base. Microfluidic systems are often composed of a number of devices that perform different functions, such as reagent mixers, sample separation devices, and sensors for analyte detection. These devices must be interconnected together to perform complex functions and must be connected to off-chip devices for sample and reagent introduction and waste removal. For most biomedical and biological lab-on-a-chip applications, the pressures in the overall system are usually fairly low, with the flow rate being the variable of interest, especially in many cell research applications.
Image processing and analysis methods for the Adolescent Brain Cognitive Development Study
The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study. •An overview of the MRI processing pipeline for the ABCD Study.•A discussion on the challenges of large, multisite population studies.•A methodological reference for users of publicly shared data from the ABCD Study.•Preliminary results from technical survey of baseline dataset.
High-throughput, real-time monitoring of engineered skeletal muscle function using magnetic sensing
Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic.
The Adult Changes in Thought (ACT) Medical Records Abstraction Project: A Resource for Research on Biological, Psychosocial and Behavioral Factors on the Aging Brain and Alzheimer’s Disease and Related Dementias
Background: Adult Changes in Thought (ACT), a prospective cohort study, enrolls older adult members of Kaiser Permanente Washington. We describe an ambitious project to abstract medical records facilitating epidemiological investigation. Methods: Abstracted data include medications; laboratory results; women’s health; blood pressure; physical injuries; cardiovascular, neurological, psychiatric and other medical conditions. Results: Of 1419 of 5763 participants with completed abstractions, 1387 (97.7%) were deceased; 602 (42.4%) were diagnosed with Alzheimer’s Disease and Related Dementias; 985 (69.4%) had a brain autopsy. Each participant had an average of 34.3 (SD = 13.4) years of data abstracted. Over 64% had pharmacy data preceding 1977; 87.5% had laboratory data preceding 1988. Stroke, anxiety, depression and confusion during hospitalization were common among participants diagnosed with dementia. Conclusions: Medical records are transformed into data for analyses with outcomes derived from other ACT data. We provide detailed, unparalleled longitudinal clinical data to support a variety of epidemiological research on clinical-pathological correlations.
The IMPART (IMproving PAlliative care in Residential aged care using Telehealth) trial: a stepped-wedge cluster-randomised controlled trial protocol
Background The quality of palliative and end-of-life care (EOLC) in residential aged care (RACFs) is variable, and often suboptimal. The aim of IMPART is to improve palliative care in RACFs. IMPART provides online training and telehealth palliative-geriatric support to aged care staff and family physicians/general practitioners (GPs) to enable timely EOLC discussions, clinical support, and improve documentation of care preferences. This may lead to preference-based care, reduction of unplanned hospitalization, and improved quality of life and EOLC. This protocol describes a study to evaluate the effectiveness, cost, and implementation process of the IMPART intervention. Methods This study is a pragmatic, stepped-wedge, cluster randomized controlled trial across 10 RACFs to evaluate the IMPART intervention. Clusters are randomly assigned to intervention or control groups. The IMPART intervention group 1) receives timely end-of-life support from specialist In-Reach teams using telehealth; 2) engages RACF staff and GPs in a Planning Ahead Team to reflect on current practices and co-design an Action Plan to improve EOLC planning and processes; 3) receives an online interactive, needs-based EOLC education program for staff and GPs working in RACFs. The control groups receive the IMPART intervention in subsequent waves. The primary outcome measure is reduction of unplanned hospital admissions and avoidable hospital transfers for residents at end-of-life when appropriate care in their RACF is possible and consistent with residents’ wishes. Secondary outcomes include reduction of emergency department presentations and length of stay of unplanned hospital admissions, and improvement in residents’ quality of life, comfort, satisfaction, and quality of EOLC. Discussion RACFs are high-mortality settings, yet the quality of palliative and EOLC varies across facilities. There is an urgent need for timely and integrated high-quality palliative care delivered in this context. Implementing IMPART, as a novel telehealth intervention, aims to address this need. This large multisite trial will provide robust evidence about the impact of the intervention (efficacy, cost-effectiveness, and process evaluation), to inform future roll-out and scale-up into the residential aged care sector. Trial registration anzctr.org.au; ACTRN12622000760774. Prospectively registered on 27/05/2022.