We are a noninvasive technologies laboratory, building devices that can manipulate and sense tissue from the surface. We are focussed in two research areas:
Noninvasive Microsurgery for Brain Drug Delivery
Wearable Controllers for Immersive Virtual Reality and Augmented Reality
NONINVASIVE MICROSURGERY SURGERY
Neurological diseases
Neurological diseases are untreatable, not due to the unavailability of drugs, but because the drugs cannot be delivered to the brain.
Along the brain's tiniest vessels, is a blood-brain barrier interface, which regulates what goes into and out of the brain. We are building technologies that can deliver drugs across this blood-brain barrier with excellent control and precision.
Our technology uses microbubbles and a noninvasive acoustic control device. Microbubbles are co-administered into the bloodstream with the drug of interest. Ultrasound is then used to drive the microbubbles into oscillations, altering the permeability of the blood-brain barrier, allowing drugs temporary passage into the brain.
Acoustic Wavelets
Our expertise is in the use of acoustic wavelets, which means small waves, to control the microbubbles. Wavelets have a low acoustic pressure and an ultra-short pulse duration. By packing the acoustic energy into such a small unit, the microbubbles produce a gentle stimulation of the blood-brain barrier.
Acoustic wavelets can deliver drugs across the the blood-brain barrier in a noninvasive and localised manner. (a) Acoustic wavelets were focused onto the left hippocampus of mice while leaving the right hippocampus unexposed. (b) Systemic injection of drugs with microbubbles resulted in the opening of the blood-brain barrier in the ultrasound exposed region. Here, a drug was modelled as a fluorescent probe (dextran, molecular weight: 3 kDa), which extravasated into the brain tissue. (c) No drug extravasation was observed in the right hippocampus. (d, e) If the drug is administered 10 minutes after exposure to acoustic wavelets, no BBB opening is observed, meaning that the BBB has closed. Zoomed in images of (b) using confocal microscopy reveal a (f) diffuse distribution of the drug in the parenchyma and (g) delivery of drugs into neurons.
Acoustic wavelets can simultaneously be used as imaging pulses. The echo returned can then inform us about the procedure, in real-time.
Our long-term research goal is to have complete control of these microbubbles, so that we can perform safe, consistent, and complex procedures in the body. While drug delivery across the blood-brain barrier is our first target, we will seek to treat diseases in other organs.
Physics, Biology, Engineering
Devices
To achieve acoustic wavelet's promise of safe and consistent procedures, we need the right hardware.
We are designing an acoustic wavelet machine, one that can control microbubbles through a feedback loop. Sound is emitted from our emitters to stimulate the microbubbles. Sound is then received from the stimulated microbubbles, informing the machine on how the procedure is evolving. This signal is then processed to then craft a new acoustic wavelet to emit.
We use advanced 3D-printing techniques to rapidly protype transducer designs.
Here is a emitter-receiver stack (PZT-pvdf), which can stimulate and monitor microbubbles. The PZT is designed to emit the acoustic wavelets while the pvdf is designed to receive the microbubble emissions (broadband frequencies).
An emitter-receiver stack. An emitter (PZT) and a receiver (pvdf) were stacked using 2 matching layers; and assembled in a 3D-printed module.
We build sensors that can capture a microbubble's acoustic emissions. Larger sensors can distort the true bubble's signal, so we've also developed very small sensor arrays.
A needle hydrophone array. 8 needle hydrophones are being used to passively image sound emitted from microbubbles.
Electrical Engineering
Wave Propagation
The thick human skull can block and distort sound from focussing in the brain. We are developing ways of transmitting wavelets through the skull and are finding ways of focussing them using an all-ultrasound method. If we can pull this off, it would mean affordable technologies that can be used with more patients across the world.
Physics, Computing
Bubble Physics
We are studying how bubbles behave when exposed to ultrasound at therapeutically relevant ultrasound conditions. Some of our interests in this area are to understand how multiple bubbles interact with each other and how they generate sound that we can monitor. This could help us decipher what the acoustic feedback signals mean, allowing us to make better decisions during treatments.
Below is a simulation of ultrasound propagating through a cloud of microbubbles. As ultrasound propagates through the microbubbles, they expand and contract. These oscillations produce their own unique acoustic emissions which spread outwards. The acoustic emissions produced here are shock waves. Notice the great asymmetry in the spreading of the sound. The sound you receive with a microphone will depend on where you place it.
Acoustic emissions from an acoustic cavitation cloud. We simulated (left) an ultrasound pulse propagating through a cloud of microbubbles and (right) the unique sound that the microbubbles emit when driven by the pulse. Notice the waveforms produced from the cloud of bubbles.
Physics, Computing
Mechanisms of Drug Delivery
We study how bubbles oscillate in cerebral microvessels and interact with the tissue microenvironment. The challenge here is the brain tissue is opaque and the microbubble oscillations are at millions of times per second. We've developed a unique blood-brain barrier model and microscopes to captures these behaviours, allowing us the ability the study how microbubbles open the blood-brain barrier and deliver drugs.
Biology, Physics
Disease Targets
We are adapting our technology for the treatment of neurological diseases. We are currently focussed on delivering drugs across the blood-brain barrier for the following three diseases:
Alzheimer’s Disease in collaboration with Prof. Magdalena Sastre (Imperial), Dr. Francesco Aprile (Imperial), Prof. Nicholas Long (Imperial).
Glioblastoma Multiforme in collaboration with Dr. Nelofer Syed (Imperial)
Diffuse Intrinsic Pontine Glioma in collaboration with Prof. Chris Jones, Prof. Simon Robinson, and Prof. Gail ter Haar at the Institute of Cancer Research.
Alzheimer’s Disease, Brain Cancer, Physics
Wearable Controllers for Immersive VR/AR
We are developing wearable technologies that can track the body’s movement, including the hands, feet, and face.
This is a new technology developed in our laboratory, and will be revealing our technology in the future.
Electrical Engineering, Computing (including Machine Learning)