Periodic Reporting for period 1 - BrainWatch (Transient micromachined pressure-monitoring implants for chronic brain disorders)
Reporting period: 2019-11-01 to 2021-10-31
During this two-year project, we focused on the development of a biodegradable micromachined pressure sensor specifically for intracranial pressure measurement applications. Work packages include 1) design of a micromachined pressure sensor, 2) development of a biodegradable substrate, 3) microfabrication of a pressure sensor specifically for intracranial pressure range.
Unlike most other cells in our body, adult brain cells cannot divide and regrow which makes brain damages have permanent effects. The majority of the brain damage cases occur through traumatic events that blow or jolt to the head or indirectly through blockage of an artery known as stroke. Traumatic brain injury (TBI) is a major public health problem worldwide and is the most common cause of death and morbidity in young people. TBI incidence is increasing in high-income countries, especially in people aged >65. It is one of the major reasons for long-term disability and is highly associated with increased mortality. In European countries, >1.3M hospital discharges and >33K deaths related to TBI were identified in 2012 only. Currently, monitoring of TBI spans a narrow time window after the surgery followed by periodic hospital visits. Hydrocephalus is another major CBD that is excessive accumulation of cerebrospinal fluid (CSF) in the brain. It is the most common childhood brain disorder and the incidence rate of infantile hydrocephalus is 110 per 100,000 live births in a European cohort. There is no treatment for hydrocephalus and a shunt is used to drain excess fluid in the brain to the abdominal cavity. TBI and hydrocephalus require extensive care and monitoring after the patient is discharged from the hospital to prevent further damage to the brain. Intracranial pressure (ICP) is one of the most critical parameters to monitor for understanding disease progression. However, in current medical settings, post-surgical monitoring of pressure is inconsistently done, if at all. Therefore, oftentimes, abnormal pressures are not noted until the opportunity to prevent further damage to the brain has passed, making a repeat intervention required.
The goal of this project is to develop implants that can monitor ICP outside hospital settings and provide important insights that could allow early diagnosis and give time for medical interventions and therapies.
A transient implant was proposed in this project, by integrating biodegradable-MEMS (B-MEMS) sensor and antenna for wireless continuous ICP monitoring applications. The implant allows monitoring outside hospital settings and would lead to better diagnostics and treatment approaches without the need for implant extraction surgery and infection risk.
The main results achieved during the project period are:
• Multiphysics simulations were carried out by considering 1 mm2 footprint for the pressure sensor. As a conclusion design parameters were clarified and optimized for the related pressure range.
• We developed a micromachining process considering standard cleanroom equipment and limitations.
• We developed an electrochemical setup to obtain a porous silicon, which enables us to utilize silicon substrate as a biodegradable material.
• The device was successfully fabricated in a cleanroom as a single pressure sensor and in array form to increase capacitance output per pressure input.
• In vitro characterization step is ongoing.
Unlike most other cells in our body, adult brain cells cannot divide and regrow which makes brain damages have permanent effects. The majority of the brain damage cases occur through traumatic events that blow or jolt to the head or indirectly through blockage of an artery known as stroke. Traumatic brain injury (TBI) is a major public health problem worldwide and is the most common cause of death and morbidity in young people. TBI incidence is increasing in high-income countries, especially in people aged >65. It is one of the major reasons for long-term disability and is highly associated with increased mortality. In European countries, >1.3M hospital discharges and >33K deaths related to TBI were identified in 2012 only. Currently, monitoring of TBI spans a narrow time window after the surgery followed by periodic hospital visits. Hydrocephalus is another major CBD that is excessive accumulation of cerebrospinal fluid (CSF) in the brain. It is the most common childhood brain disorder and the incidence rate of infantile hydrocephalus is 110 per 100,000 live births in a European cohort. There is no treatment for hydrocephalus and a shunt is used to drain excess fluid in the brain to the abdominal cavity. TBI and hydrocephalus require extensive care and monitoring after the patient is discharged from the hospital to prevent further damage to the brain. Intracranial pressure (ICP) is one of the most critical parameters to monitor for understanding disease progression. However, in current medical settings, post-surgical monitoring of pressure is inconsistently done, if at all. Therefore, oftentimes, abnormal pressures are not noted until the opportunity to prevent further damage to the brain has passed, making a repeat intervention required.
The goal of this project is to develop implants that can monitor ICP outside hospital settings and provide important insights that could allow early diagnosis and give time for medical interventions and therapies.
A transient implant was proposed in this project, by integrating biodegradable-MEMS (B-MEMS) sensor and antenna for wireless continuous ICP monitoring applications. The implant allows monitoring outside hospital settings and would lead to better diagnostics and treatment approaches without the need for implant extraction surgery and infection risk.
The main results achieved during the project period are:
• Multiphysics simulations were carried out by considering 1 mm2 footprint for the pressure sensor. As a conclusion design parameters were clarified and optimized for the related pressure range.
• We developed a micromachining process considering standard cleanroom equipment and limitations.
• We developed an electrochemical setup to obtain a porous silicon, which enables us to utilize silicon substrate as a biodegradable material.
• The device was successfully fabricated in a cleanroom as a single pressure sensor and in array form to increase capacitance output per pressure input.
• In vitro characterization step is ongoing.
1- Design and modeling of sensor and antenna: We developed models for sensor and antenna to evaluate their electro-mechanical and wireless performance, respectively. We utilized finite element models and analytical modeling for the estimation of the design parameters.
2- Fabrication of the CICPM implant components and integration: In this phase, we worked on developing a fabrication flow for the optimized sensor and antenna designs using microfabrication techniques. We developed a porous silicon development process which allowed us to develop a substrate layer. We developed the majority of the steps but the last step is still ongoing.
3- Characterization of the sensor: Due to our ongoing efforts in the cleanroom for microfabrication we couldn't fully characterize the sensor. We were able to characterize the biodegradation rate of the porous silicon layer for our application. After successful fabrication, we plan to finalize sensor characterization studies.
During the project period exploitation and dissemination studies include:
• Presentation to medical doctors related to the technology
• Presentation to undergraduate engineering students to create awareness about the disease and developed implant technology
• Presentation to academic community at IEEE conference
• Presentation to high school students
• Microfabrication studies related to the developed process were submitted as a journal paper to Advanced Materials, which is now under review.
2- Fabrication of the CICPM implant components and integration: In this phase, we worked on developing a fabrication flow for the optimized sensor and antenna designs using microfabrication techniques. We developed a porous silicon development process which allowed us to develop a substrate layer. We developed the majority of the steps but the last step is still ongoing.
3- Characterization of the sensor: Due to our ongoing efforts in the cleanroom for microfabrication we couldn't fully characterize the sensor. We were able to characterize the biodegradation rate of the porous silicon layer for our application. After successful fabrication, we plan to finalize sensor characterization studies.
During the project period exploitation and dissemination studies include:
• Presentation to medical doctors related to the technology
• Presentation to undergraduate engineering students to create awareness about the disease and developed implant technology
• Presentation to academic community at IEEE conference
• Presentation to high school students
• Microfabrication studies related to the developed process were submitted as a journal paper to Advanced Materials, which is now under review.
We developed a single-layer capacitive sensor which is superior to the state-of-the-art capacitive sensors. Conventional sensors utilize double plate capacitors, which require two metallization steps during the microfabrication. It makes fabrication challenging and makes the sensor response highly non-linear.
Here, we proposed interdigitated circular ring electrodes on the substrate. Deformation of the membrane allows linear capacitance change. Besides, the single layer structure allows building the device with a single step metallization process.
This easy microfabrication process will allow the implementation of such pressure sensor design in various other applications, which require continuous pressure sensing with linear output.
Potential impacts of the results achieved are:
• Continuous post-operative monitoring of brain trauma, hydrocephalus, and brain diseases which ICP may have a role
• New understanding of the importance of ICP for brain and cardiovascular diseases
• Wireless monitoring implants with bioresorbable materials
• Microfabrication of bioresorbable microsystems
Here, we proposed interdigitated circular ring electrodes on the substrate. Deformation of the membrane allows linear capacitance change. Besides, the single layer structure allows building the device with a single step metallization process.
This easy microfabrication process will allow the implementation of such pressure sensor design in various other applications, which require continuous pressure sensing with linear output.
Potential impacts of the results achieved are:
• Continuous post-operative monitoring of brain trauma, hydrocephalus, and brain diseases which ICP may have a role
• New understanding of the importance of ICP for brain and cardiovascular diseases
• Wireless monitoring implants with bioresorbable materials
• Microfabrication of bioresorbable microsystems