Cell-specific ultrasound neuromodulation
Ultrasonic brain stimulation is an encouraging alternative with the advantages of non- invasiveness, fine spatiotemporal control, and deeper tissue penetration. It is considered as a promising method for studying human brain functions and curing brain disorders. We have developed “sonogenetics”, which uses heterologously-expressed mechanosensitive ion channels to sensitize the desired cells for ultrasonic activation at an intensity lower than the required threshold for other non-transduced cells to minimize ultrasound induced activities from the endogenous mediators (Cell Report 2022, PNAS 2023). In this part, we plan to enhance the sonogenetic technology, characterize its performance and evaluate its potential in treating brain disorders, benchmark its effectiveness to existing approaches, and examine the biosafety.
Physical stimuli responsive nanoplatforms-enabled optogenetics
The objectives of this part are to design and fabricate nanoplatforms doped with various luminescent metal-ions (e.g., lanthanide, transition metal-ions) which are capable of responding to external physical stimuli including low-dose soft X-ray, magnetic-field and ultrasound wave, and to systematically investigate their fundamental physics relevant to energy conversion from different physical stimuli to emitted-light. Taking advantage of the new generation highly penetrative and remote stimuli-activated luminescence nanoplatforms as light nano-transducers, we will explore and demonstrate selected cutting-edge luminescence-triggered noninvasive optogenetics for modulating brain activity. The success in our pilot works including first observation of magnetic-field induced luminescence and piezo-photonics effect, as well as biomedical applications using various metal-ion doped nanophosphors lay down crucial foundations of achieving these objectives (Nature Communications 2024, Advanced Materials 2021). We will characterize and understand structural, optical spectroscopic, biocompatibility, stimuli activations and photon management properties of the nanoplatforms by combining experimental observations with theoretical modeling and simulation. Through the collaboration, our innovative strategies will enable us not only to advance scientific knowledge of the unexploited properties in metal-ion doped luminescent nanoplatforms, but also to pave the way for novel biomedical applications, which will produce great impacts on materials science, nanotechnology and biomedical fields.
Minimally invasive electrophysiology measurement
Miniaturization of biosensors has become an imperative demand because of its great potential in in vivo measurement and monitoring of brain activities of live animals. We plan to develop an ultraminiature optical fiber-tip biosensor based on the plasmonic gold nanoparticles (AuNPs) directly printed upon the end face of a standard multimode optical fiber at visible light range. An in-situ precision photoreduction technology will be developed to additively print the micropatterns of size-controlled AuNPs. The AuNPs reveal distinct localized surface plasmon resonance, whose peak wavelength provides an ideal spectral signal for label-free biodetection. The fabricated optical fiber-tip plasmonic biosensor will not only detect antibody, but also test neurotransmitters at low concentration. Such an ultraminiature fiber-tip plasmonic biosensor offers a cost-effective biodetection technology for a myriad of applications in neuroscience and neurology (Nano Energy 2019, ACS Nano 2018).
Develop advanced brain imaging technology
Functional MRI (fMRI) is an important brain imaging technique, which measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. UBSN has installed two MRI system for brain imaging of human and small animals, which will allow investigation of diseased brain functions noninvasively (Neuroimage 2021, JAMA 2019). Optical brain imaging has seen decades of intense development, and has grown into a rich and diverse field. In vivo imaging using light provides unprecedented sensitivity to functional changes through intrinsic contrast, and is rapidly exploiting the growing availability of exogenous optical contrast agents. Light can be used to image microscopic structure and function in vivo in exposed animal brain, while also allowing noninvasive imaging of hemodynamics and metabolism in a clinical setting. Functional near infrared spectroscopy (fNIRS), fiber photometry, miniscope, photoacoustic imaging are the available techniques in PolyU to study the healthy and diseased brains.
Treatment of brain disorders with neuromodulation
Brain disorders are a broad range of pathological conditions creating problems in the brain such as movements or mental functions. Take neurodegenerative diseases as an example, which have drawn attention among the diseases because of its complexity in causes and symptoms, lack of proper effective treatment(s), no report of irreversibility, and poor impact on social and financial aspects. AD as a common neurodegenerative disease affects more than 47 million people worldwide. It impairs people's memory and cognitive function, affects people's normal life, and brings a heavy burden to the family and community. Drugs have been used clinically, still they have not delayed or reversed AD's development. The research team already has expertise in TMS, electric, US, and optogenetic stimulation of depression, PD, AD, epilepsy etc. with relevant equipment under UBSN. The establishment of the research center will bring multi-modality methods together for comprehensive and complementary treatment trials.
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