Imec at Holst Centre’s chip technology enabled liquid sensing platforms: Revolutionising continuous multi-parametrical biochemical sensing

 

Imec at Holst Centre’s vision is to enable continuous multi-parametrical biochemical sensing in a miniaturised format. Such a compact, durable, and scalable chip technology allowing inline, online and at-line measurements, has the potential to cater to a wide range of applications in biomanufacturing, organ-on-chip systems, and implantables.

Whether for in-body autonomous measurements of biochemical parameters for personal treatments or continuous inline multi-well measurement of organ-on-chip applications, there’s a growing need for sensing technologies that continuously monitor multiple key parameters. Imec’s miniaturised sensing solutions can be adapted to a wide range of form factors as needed by specific applications.

Scalable, miniaturised sensor technology

Imec has decades-long experience in biochemical sensing. Sneha, Program Manager, Liquid Sensing Technologies at imec at Holst Centre, states, “Imec has been a frontrunner in micro-fabrication and nanotechnology, integrating not only electronic circuits but also microfluidicsphotonicssensors and actuators at the wafer level. Using advanced packaging techniques that meet specific application requirements, our miniaturised sensor technology can pack a variety of parameters onto a small, compact device, such as a probe or a flow cell. At the same time, we aim to bridge the gap towards manufacturability and scalability, moving from lab prototypes to high-volume production.”

Three key domains

Currently, imec sees three key application domains for its biochemical sensing platform. Sneha explains: “We have already successfully demonstrated the benefits of real time monitoring of critical process parameters for biomanufacturing, and now we are also looking to impact the domains of organ-on-chip and in-body applications for continuous in vivo sensing. What these three domains have in common is the need for biocompatibility or non-cytotoxicity, sterilisability, miniaturisation, continuous sensing on multiple parameters, with lifetimes varying from a few days to even years.”

 

1. Biomanufacturing

By leveraging the compactness and affordability of chip technology, imec is developing a multiparameter sensor solution for process analytics that brings continuous quality and process control to biomanufacturing (Figure 1). Currently, offline bioprocess monitoring is still the norm, with samples taken out manually, disturbing the process flow. This means that for personalised treatments such as cell and gene therapy, valuable time is lost for the patient. By offering constant real-time inline/online monitoring – even automatic – adjustment of the production steps increases yield, reduces waste, and cuts cycle times.

Figure 1: Imec’s multiparameter solution for process analytics is conceived as a single probe that’s immediately deployable, remains stable for at least four weeks and can wirelessly transfer data. The picture depicts the sensor chip and the PCB holding the chip. In a fully assembled probe, there is a cap covering and protecting the PCB connections and only the sensor chip is exposed to the liquid around.
2. Organ on chip

Despite significant investments in drug discovery, the number of drugs that successfully reach the market remains low. Organ-on-chip technology holds the promise of reducing animal testing and enhancing the drug development process. Imec is making substantial contributions to the organ-on-chip ecosystem by leveraging various in-house capabilities on advanced microfluidics, electronics, data analytics and sensors.

We are developing a miniaturised multiparametric sensor platform in the form of a flow cell leveraging the power of wafer scale fabrication and packaging techniques. The sensor architecture is compatible with standard 96 well plate format (Figure 2). The ability to measure various biochemical processes and biomarkers simultaneously and directly in the multi-well plate from a tiny amount of fluid will bring substantial cost and time savings in disease research and drug discovery processes. This advanced multi-well solution offers major advantages in addition to current imaging or end-point testing, where cell material is often wasted. With great detail, we can measure the cells' response to drugs, toxicity, and various parameters indicative of cell health, cell stress, inflammatory markers, or cell function markers, depending on the cell types being researched.

 

The flux of real-time data that is generated, combined with AI, could help uncover new information for personalised medicine, therapy, or drug discovery. Moreover, this multi-well solution offers high throughput and scalability, making it a significant advancement over traditional methods.

Figure 2: Miniaturised and multi-electrode sensor (>50) architecture in the form of flow cell, manufactured using wafer scale fabrication and packaging techniques.
3. In-body monitoring

Imec’s liquid sensing solutions could also contribute to other promising future health applications, such as personalised therapeutics and preventive healthcare. This technology holds the promise to lighten the load on our healthcare system by shifting towards wearables, careables, and implantables for diagnostics and therapeutic care. Automated closed-loop solutions like implantables offer more effective patient-specific treatments, resulting in higher care quality and lower healthcare costs.

 

For instance, our sensing solution could contribute to preventive healthcare by identifying the onset of inflammation or infection, allowing for preventive measures and timely actions towards specific treatments. Additionally, advanced sensors could continuously monitor patients, eliminating the need for medical staff to take blood or urine samples multiple times a day. This automated monitoring and data management could help keep healthcare accessible and affordable for all, while simultaneously reducing the workload for healthcare professionals by contributing to workflow efficiency.

 

Let’s innovate together

For these applications, imec is seeking collaboration with both industry partners and end users to further develop and validate its liquid sensing technology portfolio. For organ-on-chip, we aim to establish partnerships with pharmaceutical companies that recognise the potential of transitioning from animal trials to organ-on-chip technologies. We are also open to forming a consortium with interested parties who see the value in our organ-on-chip work and wish to collaborate on grant applications and shared research initiatives.