This research is laying the foundation for an exciting new generation of biomedical devices. This work is a timely, interdisciplinary collaborative effort. It represents a close and synergistic collaboration among biological and medical scientists, biomedical engineers and electrical engineers.
It is dependent on our close partnership with our engineering colleagues at Purdue University, in particular Dr. Pedro Irazoqui (see Visiting Investigators and Intellectual Community). Dr. John and Dr. Irazoqui have forged a strong and close team, spending time at each institution with multiple visits in each direction each year. They have founded a biomedical engineering laboratory at The Jackson Laboratory, which allows critical innovation, development, fabrication, and experimentation. It is enabling multidisciplinary interactions to extend to other groups. It allows frequent exchange of students and postdoctoral fellows between our institutions, promoting both multidisciplinary training and research.
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The need for miniature implantable devices
The ability to constantly collect long-term physiological data without disturbing experimental animals remains a challenge. Additionally, the ability to collect such data in human patients in their normal lives is difficult. Collecting this long term data in very small compartments within an animal or human is an added challenge and is often impossible. Ultimately, we aim to develop a series of ultra-miniature tools that will overcome these challenges and allow long term monitoring within very small spaces. These miniaturized tools will have potential to transform physiologic monitoring in biomedicine and other applications. In the long term, we envision networks of smart, miniaturized tools that communicate and respond to each other in real time. Networked devices will interact to both monitor disease and administer timely treatments. For example, a miniature pressure sensor may directly communicate with a pump that delivers medications. Thus, our development of these devices has great potential to revolutionize both research abilities and clinical treatment.
Mouse sized devices will be useful in larger species & human patients
To ensure the value of these devices for breaking open new research areas, a major focus is the development of devices designed for mice. Mice have a similar physiology to people and develop the same diseases. The mouse provides a very powerful experimental system for understanding diseases. In each case, the new devices that we will develop will allow experiments that are not possible using current technology. Scaling the devices to fit mice ensures that they can be used in larger species, human medical research and in clinical medicine.
A miniature control and interrogation platform
The unifying theme of our team's efforts is the development and implementation of a miniature, integrated, powering, control and interrogation platform. This platform will allow remote and automated phenotype interrogation. Our team has already developed and miniaturized technologies to allow powering and interrogation of tiny implantable tools. After final development, this miniature platform can be refined for a multitude of uses by coupling with different sensors and tools. It will wirelessly control and monitor completely implantable, miniature devices. This technology will represent an important advancement in the use of integrated, low power, miniature, sensing systems in wireless networks of devices.
Ultra-miniature device to measure IOP in mice
Currently, we are focusing on a device to measure intraocular pressure. IOP is not a static parameter but changes considerably even within a single day. The variability of IOP complicates the study of pressure-induced RGC degeneration in glaucoma. Existing technologies for monitoring IOP are limited and technicians make measurements periodically. These periodic measurements may not capture the full range of IOP fluctuation. Therefore, we do not accurately know the duration or magnitude of IOP within any eye that develops glaucoma. Additionally, devices requiring an investigator to be present are not practical for around the clock monitoring and can result in significant disturbance that can alter the pressure reading. Our inability to routinely measure IOP continuously over time limits the progress of research, and ultimately, hinders the management of human glaucoma.
We are developing an ultra-miniature, integrated device that will allow remote interrogation of IOP in mice. This miniature device will make possible automated, long term and essentially continuous monitoring of IOP. It will allow improved understanding of the link between high IOP and glaucomatous neurodegeneration, and it has powerful implications for future clinical use.
Our groundbreaking technology allows our new device to be significantly smaller than any existing device. The device will be completely implanted inside the eye. It will be small enough to fit within the mouse anterior chamber, which has a volume of approximately 5 µl (one tenth the volume of a drop). It will contain an application-specific integrated circuit (ASIC) and an antenna that will remotely power and program the device to transmit collected data to a receiver. It will be possible to continuously monitor the IOPs of hundreds of mice in the same animal room. Automated and remote IOP monitoring using a wireless sensor will greatly facilitate research to understand glaucoma and will ultimately improve the future care of patients.
The development of this device represents both a breakthrough in engineering and the potential to revolutionize mechanistic understandings of glaucoma, and other conditions related to fluid pressure.Other devices
To allow currently impractical experiments, drive new research directions and improve patient care, we are keen to develop a series of miniature, sensing systems and tools. For example--and although additional funding is required for their development--useful new devices would improve monitoring of blood pressure and cerebrospinal fluid pressure (CSF). In addition to each of their own importance, both blood pressure and CSF pressure may have significant influences on glaucoma. Improved continuous and remote monitoring of CSF pressure would enhance research into hydrocephalus and may advance clinical care. Other devices may measure electrical activity in muscle and advance research into ALS and muscular dystrophies.
Support our Research Facilitate the development of an exciting new generation of medical devices.Neurobiology of Glaucoma Neuroprotection Genetics of IOP Elevation and Glaucoma Human Glaucoma Collaborations
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