Periodic Reporting for period 1 - SmOoC (Smart organ-on-chip platform based on higher order multimode acoustic Lamb waves)
Reporting period: 2020-06-01 to 2022-05-31
Organ-on-chip (OoC) is a remarkable example of the convergence of biology and microengineering. OoC has a great potential to revolutionize the current existing in-vitro approach to drug discovery and development, resulting in a reduction in the need for animal experiments and accelerating the research and development process for future precision and personalised medicine. However, the complexity of the system is a hurdle in the transfer of the OoC system from laboratory to large-scale manufacturing and commercial application. The miniaturisation and integration of sensing and actuation components is an important aspect to be addressed to ensure the manufacturability of the system. Moreover, a closed-loop control system is required to create a smart OoC system that can operate dynamically to process the information and make decisions in a predictive or adaptive manner.
The objective of this proposed research project is to develop a smart OoC system by utilising multimode Lamb waves for sensing, actuation, and control, integrated within a microfluidic system. Furthermore, for OoC with a multi-chamber microfluidic system, a porous membrane is required for channel separation and communication. At the end of the project, we have successfully developed a miniaturised plate acoustic wave (PAW)-based biosensor that offers simple and direct integration with a microfluidic channel. In addition to the scaling down in term of geometry, the miniaturisation of the sensor increases the operating frequency of the sensor which also increase the theoretical sensitivity of the sensor. Furthermore, we have designed and fabricated a silicon-based porous membrane which offers flexibility in designing the membrane geometry, in terms of thickness, porous size and porosity. The design of the sensor and the membrane as well as the choice of material allow us to fabricate a PDMS-free organ-on-chip platform, which will be suitable for some applications such as drug-organ interaction, Furthermore, the fabrication process flow is based on standard semiconductor clean room fabrication process which will allow direct integration with CMOS-based integration circuit and high volume manufacturing. Thus the result of this project will contribute to the standardisation of the OoC platform for large-scale manufacturing to achieve its potential for future personalised medicine applications.
The objective of this proposed research project is to develop a smart OoC system by utilising multimode Lamb waves for sensing, actuation, and control, integrated within a microfluidic system. Furthermore, for OoC with a multi-chamber microfluidic system, a porous membrane is required for channel separation and communication. At the end of the project, we have successfully developed a miniaturised plate acoustic wave (PAW)-based biosensor that offers simple and direct integration with a microfluidic channel. In addition to the scaling down in term of geometry, the miniaturisation of the sensor increases the operating frequency of the sensor which also increase the theoretical sensitivity of the sensor. Furthermore, we have designed and fabricated a silicon-based porous membrane which offers flexibility in designing the membrane geometry, in terms of thickness, porous size and porosity. The design of the sensor and the membrane as well as the choice of material allow us to fabricate a PDMS-free organ-on-chip platform, which will be suitable for some applications such as drug-organ interaction, Furthermore, the fabrication process flow is based on standard semiconductor clean room fabrication process which will allow direct integration with CMOS-based integration circuit and high volume manufacturing. Thus the result of this project will contribute to the standardisation of the OoC platform for large-scale manufacturing to achieve its potential for future personalised medicine applications.
The project has three research work packages :
1. development of the acoustic device based on the higher order multimode Lamb waves, with both sensor and actuation function
2. Miniaturisation of the acoustic waves devices for integration with microfluidic
3. Integration of multi-channel microfluidic system, porous membrane and sensor for a PDMS-free OoC platform
We have successfully designed plate-acoustic waves (PAW)-based devices utilising 5th and 6th symmetric Lamb modes for sensors application in a liquid environment based on piezoelectric GaAs substrate. Simultaneously, the devices will also excite other modes (such as 5th and 6th antisymmetric modes) which will radiate the acoustic energy into the liquid for liquid actuation. Thus we are able to obtain sensing and actuation functions in the same device. Furthermore, the device can be easily miniaturised by reducing the wavelength of the interdigitated transducer (IDTs) and the thickness of the plate.
We designed a miniaturised PAW-based acoustic sensor and directly integrate it into the microfluidic channel by reducing the size of the IDT and thinning down the GaAs by a bulk micromachining process. A microfluidic channel was created on the GaAs substrate with the sensing area at the opposite surface from the IDTs. Gold thin film is deposited on the sensing area for surface functionalization to capture specific biomolecules (such as extracellular vesicles, EV). The OoC platform was designed to be compatible with CMOS-based microfabrication process. Silicon-on-Insulator (SOI) wafer and standard deep reactive ion etching (DRIE) process were used to fabricate silicon porous membrane. The sensor, the porous membrane and glass wafer were integrated by standard wafer level microfabrication and bonding process.
The project has resulted in the publication of 1 journal paper, 2 conference proceedings and 1 European patent application. Furthermore, 4 possible journal paper is currently in preparation.
1. development of the acoustic device based on the higher order multimode Lamb waves, with both sensor and actuation function
2. Miniaturisation of the acoustic waves devices for integration with microfluidic
3. Integration of multi-channel microfluidic system, porous membrane and sensor for a PDMS-free OoC platform
We have successfully designed plate-acoustic waves (PAW)-based devices utilising 5th and 6th symmetric Lamb modes for sensors application in a liquid environment based on piezoelectric GaAs substrate. Simultaneously, the devices will also excite other modes (such as 5th and 6th antisymmetric modes) which will radiate the acoustic energy into the liquid for liquid actuation. Thus we are able to obtain sensing and actuation functions in the same device. Furthermore, the device can be easily miniaturised by reducing the wavelength of the interdigitated transducer (IDTs) and the thickness of the plate.
We designed a miniaturised PAW-based acoustic sensor and directly integrate it into the microfluidic channel by reducing the size of the IDT and thinning down the GaAs by a bulk micromachining process. A microfluidic channel was created on the GaAs substrate with the sensing area at the opposite surface from the IDTs. Gold thin film is deposited on the sensing area for surface functionalization to capture specific biomolecules (such as extracellular vesicles, EV). The OoC platform was designed to be compatible with CMOS-based microfabrication process. Silicon-on-Insulator (SOI) wafer and standard deep reactive ion etching (DRIE) process were used to fabricate silicon porous membrane. The sensor, the porous membrane and glass wafer were integrated by standard wafer level microfabrication and bonding process.
The project has resulted in the publication of 1 journal paper, 2 conference proceedings and 1 European patent application. Furthermore, 4 possible journal paper is currently in preparation.
We designed and fabricated a PDMS-free OoC platform with an integrated acoustic biosensor and polished silicon porous membrane. We also developed a fabrication process flow compatible with the standard CMOS-based cleanroom microfabrication process. Furthermore, we demonstrated the feasibility of the cell seeding process on polished silicon surface with collagen coating. The choice of materials and fabrication process flow are compatible with the CMOS-based microfabrication process, thus allowing the direct transfer from the research laboratory to a large-scale microfabrication manufacturing process. The result of this project will contribute to the standardisation of the OoC platform toward reaching the potential of the OoC for future precision and personalised medicine, to improve the quality of healthcare and quality of life in Europe and beyond.