Biology subjects

Shah, V.

Publications and source records attributed to Shah, V..

42 records · Page 3Linked to original sources

bioRxiv2020

Multi-Channel Whole-Head OPM-MEG: Helmet Design and a Comparison with a Conventional System

Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however such systems have fundamental limitations. In recent years quantum-enabled devices, called optically-pumped magnetometers (OPMs), have promised to lift those restrictions, offering an adaptable, motion-robust MEG device, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with whole-head coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging. HIGHLIGHTSO_LIA 49-channel whole-head OPM-MEG system is constructed C_LIO_LISystem evaluated via repeat measurements of alpha, beta and gamma oscillations C_LIO_LITwo OPM-helmet designs are contrasted, a flexible (EEG-like) cap and a rigid helmet C_LIO_LIThe rigid helmet offers significant advantages for a viable OPM-MEG device C_LIO_LI49-channel OPM-MEG offers performance comparable to established cryogenic devices C_LI

neuroscience↗

bioRxiv2019

An Addressable Microfluidics device for Noninvasive Manipulation of Cells and Chemicals within Live Cultures

According to the U.S. Department of Health & Human Services, nearly 115,000 people in the U.S needed a lifesaving organ transplant in 2018, while only [~]10% of them have received it. Yet, almost no artificial FDA-approved products are commercially available today - three decades after the inception of tissue engineering. It is hypothesized here that the major bottlenecks restricting its progress stem from lack of access to the inner pore space of the scaffolds. Specifically, the inability to deliver nutrients to, and clear waste from, the center of the scaffolds limits the size of the products that can be cultured. Likewise, the inability to monitor, and control, the cells after seeding them into the scaffold results in nonviable tissue, with an unacceptable product variability. To resolve these bottlenecks, we present a prototype addressable microfluidics device capable of minimally disruptive fluid and cell manipulations within living cultures. As proof-of-concept, we demonstrate its ability to perform additive manufacturing by seeding cells in spatial patterns (including co-culturing multiple cell types); and subtractive manufacturing by removing surface adherent cells via focused flow of trypsin. Additionally, we show that the device can sample fluids and perform cell "biopsies" (which can be subsequently sent for ex-situ analysis), from any location within its Culture Chamber. Finally, the on-chip plumbing is completely automated using external electronics. This opens the possibility to perform long-term computer-driven tissue engineering experiments, where the cell behavior is modulated in response to the minimally disruptive observations (e.g. fluid sampling and cell biopsies) throughout the entire duration of the cultures. It is expected that the proof-of-concept technology will eventually be scaled up to 3D addressable microfluidic scaffolds, capable of overcoming the limitations bottlenecking the transition of tissue engineering technologies to the clinical setting.

bioengineering↗

bioRxiv2019

PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers - first-in-human results

Major determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.

clinical trials↗

bioRxiv2019

Fluorescent biosensor for real-time interaction dynamics of host proteins with HIV-1 capsid tubes

The human immunodeficiency virus 1 (HIV-1) capsid serves as a binding platform for proteins and small molecules from the host cell that regulate various steps in the virus life cycle. However, there are currently no quantitative methods that use assembled capsid lattices for measuring host-pathogen interaction dynamics. Here we developed a single molecule fluorescence biosensor using self-assembled capsid tubes as biorecognition elements and imaged capsid binders using total internal reflection fluorescence microscopy in a microfluidic setup. The method is highly sensitive in its ability to observe and quantify binding, obtain dissociation constants, extract kinetics with an extended application of using more complex analytes that can accelerate characterisation of novel capsid binders.

biophysics↗

bioRxiv2018

Supplemental vibrotactile feedback of real-time limb position enhances precision of goal-directed reaching

We examined vibrotactile stimulation as a form of supplemental limb state feedback to enhance on-going control goal-directed movements. Subjects wore a two-dimensional vibrotactile display on their non-dominant arm while performing horizontal planar reaching movements with their dominant arm. The vibrotactile display provided feedback of hand position such that small hand displacements were more easily discriminable using vibrotactile feedback than with intrinsic proprioceptive feedback. When subjects relied solely on proprioceptive feedback to capture visuospatial targets, target capture performance was degraded by proprioceptive drift and an expansion of task space. By contrast, reach accuracy was enhanced immediately when subjects were provided vibrotactile feedback, and further improved over two days of training. Improvements reflected a resolution of proprioceptive drift which occurred only when vibrotactile feedback was active, demonstrating that the benefits of vibrotactile feedback are due in part to its integration into the ongoing control of movement. A partial resolution of task space expansion that persisted even when the vibrotactile feedback was inactive demonstrated that training with vibrotactile feedback also induced changes in movement planning. However, the benefits of vibrotactile feedback come at a cognitive cost. All subjects adopted a stereotyped, movement decomposition strategy wherein they attempted to capture targets by moving first along one axis of the vibrotactile display and then the other. For most subjects, this inefficient movement approach did not resolve over two bouts of training performed on separate days, suggesting that additional training is needed to fully integrate vibrotactile feedback into the planning and online control of goal-directed reaching.

neuroscience↗

bioRxiv2017

Frequency-dependent response of Chromobacterium violaceum to sonic stimulation, and altered gene expression associated with enhanced violacein production at 300 Hz

Chromobacterium violaceum was subjected to sonic (100-2000 Hz) stimulation, and the effect on its cell yield and quorum sensing regulated pigment (violacein) production was investigated. Sound corresponding to the 300 Hz was found to promote (by 1.52 fold) violacein production the most, with only marginal impact on cell yield. Whole transcriptome analysis revealed that a total of 342 genes (i.e. 4.63% of whole genome) were significantly up-regulated in the sonic stimulated culture. Enhanced violacein production in the sound stimulated culture seems to have stemmed from enhanced expression of the genes involved in glucose metabolism through pentose phosphate pathway, resulting in increased availability of erythrose-4-phosphate, to be used for synthesis of tryptophan, the precursor for violacein synthesis. Multiple ribosomal subunit genes, enzyme coding genes, and those associated with secretion/transport were up-regulated owing to sonic stimulation. This study is a good demonstration of the ability of sound waves to alter bacterial metabolism.

microbiology↗