Shamit Shrivastava

Shamit Shrivastava
University of Oxford | OX · Department of Engineering Science

Doctor of Philosophy

About

43
Publications
9,416
Reads
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879
Citations
Additional affiliations
March 2019 - March 2021
University of Oxford
Position
  • Senior Researcher
Description
  • www.shamits.org
Education
September 2008 - January 2014
Boston University
Field of study
  • Biomedical Engineering

Publications

Publications (43)
Article
Full-text available
Biological membranes by virtue of their elastic properties should be capable of propagating localized perturbations analogous to sound waves. However, the existence and the possible role of such waves in communication in biology remains unexplored. Here we report the first observations of 2D solitary elastic pulses in lipid interfaces, excited mech...
Article
Full-text available
Nerve impulses, previously proposed as manifestations of nonlinear acoustic pulses localized at the plasma membrane, can annihilate upon collision. However, whether annihilation of acoustic waves at interfaces takes place is unclear. We previously showed the propagation of nonlinear sound waves that propagate as solitary waves above a threshold (su...
Article
Full-text available
Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs e.g. recombinant protein, expression plasmids or mRNA), which is a major barrier for clinical translation of macrodrug-based therapies. Encapsulation of macromolecules in lipid nanoparticles (LNPs) can protect the therapeutic agent during transport t...
Article
Full-text available
The thermodynamic state of lipid interfaces was observed during shock wave induced cavitation in water with submicrosecond resolution, using the emission spectra of hydration-sensitive fluorescent probes colocalized at the interface. The experiments show that the cavitation threshold is lowest near a phase transition of the lipid interface. The cav...
Article
Action potentials in neurons are known to annihilate each other upon collision, while there are cases where they might penetrate each other. The fate of two waves upon collision is critically dependent on the underlying mechanism of propagation and therefore an understanding of possible outcomes of collision under different conditions is important....
Article
Full-text available
The thermodynamic theory of action potential propagation challenges the conventional understanding of the nerve signal as an exclusively electrical phenomenon. Often misunderstood as to its basic tenets and predictions, the thermodynamic theory is virtually ignored in mainstream neuroscience. Addressing a broad audience of neuroscientists, we here...
Preprint
Full-text available
Preprint now published in Progress in Biophysics and Molecular Biology: Action potentials in neurons are known to annihilate each other upon collision, while there are cases where they might penetrate each other. The fate of two waves upon collision is critically dependent on the underlying mechanism of propagation and therefore an understanding of...
Preprint
Full-text available
It has previously been suggested that the plasma membrane condenses and melts reversibly during an action potential in a neuron. If true it has fundamental consequences for our understanding of the regulation of biological functions during an action potential. It has long been known that the electrical dipoles in the neuronal membrane reorient duri...
Article
Microbubbles stabilised by an outer lipid shell have been studied extensively for both diagnostic and therapeutic applications. The shell composition can significantly influence microbubble behaviour, but performing quantitative measurements of shell properties is challenging. The aim of this study was to investigate the use of spectral imaging to...
Preprint
Full-text available
This study investigates the emission of light and sound from cavitation caused by intense pressure pulses in water. Based on time-resolved measurements of (a) pressure waveform at the focus, (b) light scattering upon cavitation, (c) acoustic emission, and (d) photoemission (sonoluminescence) it is shown that emissions occur upon the creation or exp...
Article
Full-text available
The intense conditions generated in the core of a collapsing bubble have been the subject of intense scrutiny from fields as diverse as marine biology and nuclear fusion. In particular, the phenomenon of sonoluminescence - whereby a collapsing bubble emits light - has received significant attention. Sonoluminescence has been associated predominantl...
Article
Full-text available
Ultrasonic neuromodulation is a rapidly growing field, in which low-intensity ultrasound (US) is delivered to nervous system tissue, resulting in transient modulation of neural activity. This review summarizes the findings in the central and peripheral nervous systems from mechanistic studies in cell culture to cognitive behavioral studies in human...
Preprint
Full-text available
The thermodynamic state of lipid interfaces was observed during shock wave induced cavitation in water with sub-microsecond resolution, using the emission spectra of hydration-sensitive fluorescent probes co-localized at the interface. The experiments show that the cavitation threshold is lowest near a phase transition of the lipid interface. The c...
Article
High-intensity focused ultrasound (HIFU) is often used to create lesions, or regions of tissue destruction due to heating and cavitation activity, most often in tumors or other diseased tissues. However, the acoustic properties of tissues denatured by heat are not very different from those of untreated tissue, making lesion detection and quantifica...
Article
Full-text available
The advancement of ultrasound-mediated therapy has stimulated the development of drug-loaded microbubble agents that can be targeted to a region of interest through an applied magnetic field prior to ultrasound activation. The need to incorporate therapeutic molecules while optimising responsiveness to both magnetic and acoustic fields, and maintai...
Article
Full-text available
Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the i...
Article
Full-text available
Ultrasound is increasingly being used to modulate the properties of biological membranes for applications in drug delivery and neuromodulation. While various studies have investigated the mechanical aspect of the interaction such as acoustic absorption and membrane deformation, it is not clear how these effects transduce into biological functions,...
Conference Paper
Full-text available
In this paper, we propose a simple acoustofluidic method for production of microbubble contrast agents in disposable microfluidic chips by the use of a low-frequency ultrasound transducer and a temperature controller unit. The technique is used to increase the lifetime and to narrow down the size distribution of the microbubbles as compared to trad...
Preprint
Full-text available
Paper Accepted in PR Materials. Updated Preprint available at https://arxiv.org/abs/1808.03904 Ultrasound and shock waves have been shown to alter the permeability and/or the polarization of cell membranes. The phenomenon of cavitation is believed to play a major role in these interactions, but the mechanism is not clear due to lack of direct obs...
Article
Full-text available
The plasma membrane undergoes reversible structural changes as a collective system of lipids and proteins during the propagation of an action potential. Recently it has been shown that 2D compression waves propagating in a lipid monolayer at the air-water interface behave exactly like action potentials, in the complete absence of any protein channe...
Preprint
Lipid interfaces not only compartmentalize but also connect different reaction centers within a cell architecture. These interfaces have well defined specific heats and compressibilities, hence energy can propagate along them analogous to sound waves. Lipid monolayers prepared at the air-water interface of a Langmuir trough present an excellent mod...
Article
Full-text available
We derive the nonlinear fractional surface wave equation that governs compression waves at an interface that is coupled to a viscous bulk medium. The fractional character of the differential equation comes from the fact that the effective thickness of the bulk layer that is coupled to the interface is frequency dependent. The nonlinearity arises fr...
Conference Paper
The blood-brain barrier (BBB) can be locally, non-invasively, and transiently opened by exposing circulating cavitation agents, such as clinically-approved contrast-agent microbubbles, to an ultrasound field. The safety and efficacy of ultrasound-mediated BBB disruption is currently under investigation in human clinical trials yet the mechanisms un...
Article
Experimental results are presented on the acoustic propagation of mechanical perturbations in a lipidmonolayer along the air-water interface. The interface was excited by a piezo-cantilever, and propagating impulses were measured optically using Forster ResonanceEnergy Transfer (FRET). The velocity of propagation varied from 0.1 to 1 m/s depending...
Conference Paper
Blood-brain barrier (BBB) disruption mediated by ultrasound and microbubbles (US-BBBD) is a promising strategy for non-invasive and targeted delivery of therapeutics to the brain. In US-BBBD, treatment control is achieved by externally monitoring acoustic emissions(AE) and adjusting ultrasound parameters in real-time to avoid AE associated with dam...
Poster
Here we investigate the cavitation phenomenon at a lipidinterface of multilaminar vesicles (MLVs) subjected to acoustic shock waves. The lipid membranes contain a fluorescent dye, Laurdan, which produces a fluorescence emission sensitive to the thermodynamic state of the interface.Fluorescence emissions were measured at 438nm and 470nm using two ph...
Conference Paper
Full-text available
The mechanisms underpinning sonoporation – the permeabilization of cell membranes following exposure to ultrasound and microbubbles – remain a source of considerable uncertainty1. Moreover, recent studies have indicated that reversible permeabilisation can be induced by extremely mild ultrasound exposure conditions2,3. In this study we investigate...
Preprint
Ultrasound is increasingly being used to modulate the properties of biological membranes for applications in drug delivery and neuromodulation. While various studies have investigated the mechanical aspect of the interaction such as acoustic absorption and membrane deformation, it is not clear how these effects transduce into biological functions,...
Article
Full-text available
Local changes in pH are known to significantly alter the state and activity of proteins and in particular enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. the lipid bilayer) would therefore constitute an important pillar towards a new physical mechanism of biochemical regulation and biological signaling. Here we inve...
Article
Full-text available
This study shows that the stability of solitary waves excited in a lipid monolayer near a phase boundary requires positive curvature of the adiabats, a known necessary condition in shock compression science. It is further shown that the condition results in a threshold for excitation, saturation of the wave amplitude and the splitting of the wave a...
Preprint
Biological membranes by virtue of their elastic properties should be capable of propagating localized perturbations analogous to sound waves. However, the existence and the possible role of such waves in communication in biology remains unexplored. Here we report the first observations of 2D solitary elastic pulses in lipid interfaces, excited mech...
Thesis
Full-text available
Biological macromolecules self-assemble under entropic forces to form a dynamic 2D interfacial medium where the elastic properties arise from the curvature of the entropic potential of the interface. Elastic interfaces should be capable of propagating localized perturbations analogous to sound waves. However, (1) the existence and (2) the possible...
Data
Self-quenching in NBD dyes. DMPC-NBD intensity-area isotherms for a temperature range of 5 to 14 C. The quenching effects are much more pronounced in DMPC-NBD system as compared to DPPC-NBD system. On top is the plot for monolayers with 0.1% NBD. The bottom plot is for NBD concentration of 1% by mole. For the 10 fold increase in concentration of th...
Data
Intensity-Area isotherms. Intensity plotted as a function of area per molecule for isotherms of DPPC-NBD monolayer. That the slopes during transition are conserved (fig. 3b) is elaborated here by the parallel nature of the curves. This graph is essentially the projection of the 3D state diagram of figure 3 on the [I-A] plane. Except in the isotherm...
Data
Non-equilibrium Opto-mechanical coupling. The note explains the relationship between the mechanical and optical data. Opto-mechanical data can be used to correctly estimate the velocity of propagation, which is also accessible experimentally, showing the self consistency of the approach. (DOCX)
Data
Opto-mechanical coupling coefficient. Intensity and surface pressure as a function of area per molecules for a DPPC-NBD monolayer during a quasi-static compression. The plateau in the pressure curve, which represents the LE-LC coexistence region, is correlated with an abrupt but steady rise in intensity indicating intensity is most sensitive to sma...
Data
State dependence of the coupling is conserved for different dyes. Intensity as a function of lateral pressure for DMPC/BODIPY(left) and DMPC/Texas Red (right) (both had 0.1% dye by moles) at several different temperatures. The arrow marks the direction of increasing temperature. The intensity goes through an abrupt increase as a function of surface...
Article
Full-text available
Fluorescent dyes are vital for studying static and dynamic patterns and pattern formation in cell biology. Emission properties of the dyes incorporated in a biological interface are known to be sensitive to their local environment. We report that the fluorescence intensity of dye molecules embedded in lipid interfaces is indeed a thermodynamic obse...
Conference Paper
Einstein founded statistical physics on an important generalization of the Boltzmann principle: Einstein's reversion, where not the model but the law of entropy is placed first. The advantage is that it assures the 2nd Law and requires no model assumptions. In particular, the existence of a complete molecular mechanism is not necessary. However, if...
Article
Immobilization of cells inside microfluidic devices is a promising approach for enabling studies related to drug screening and cell biology. Despite extensive studies in using grooved substrates for immobilizing cells inside channels, a systematic study of the effects of various parameters that influence cell docking and retention within grooved su...
Article
Directed embryonic stem (ES) cell differentiation is a potentially powerful approach for generating a renewable source of cells for regenerative medicine. Typical in vitro ES cell differentiation protocols involve the formation of ES cell aggregate intermediates called embryoid bodies (EBs). Recently, we demonstrated the use of poly(ethylene glycol...
Conference Paper
Full-text available
Finite Element Method (FEM) is applied for numerical analysis of SMA beam fixed at both the ends. Shape memory alloys (SMAs) like Nitinol (Nickel-Titanium alloy) are well known materials capable of recovering extremely large inelastic strain (of the order of 10%) by the Martensite-Austenite phase transformation. The shape memory effect (SME), pseud...

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Projects

Projects (3)
Project
To establish thermodynamic relationships through observations between the state of the interface and various aspects of the fluorescence emission of embedded molecular probe(s). This includes Intensity and polarization, spectra, forster resonance energy transfer between multiple fluorescent probes, and fluorescence correlation) during static and dynamic processes at the interface.
Project
Biological macromolecules self-assemble under entropic forces to form a dynamic 2D interfacial medium where the elastic properties arise from the curvature of the entropic potential of the interface. Elastic interfaces should be capable of propagating localized perturbations analogous to sound waves. However, (1) the existence and (2) the possible role of such waves in affecting biological functions remain unexplored. Both these aspects of “sound” as a signaling mechanism in biology are to be explored experimentally on mixed monolayers of lipids-fluorophores-proteins at the air/water interface as a model biological interface.
Project
To understand the thermodynamic basis of cavitation phenomenon at lipid interfaces. To obtain a relation between the cavitation characteristics and the thermodynamic state of the system. Not only how the state of the interface changes during an acoustic insult with or without cavitation but also the state might itself control the cavitation statistics at the interface. Understanding these effects is crucial for applications in controlled sonoporation, drug delivery and neuromodulation in native biological environments.