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Next Generation Lab-On-a-Chip For Advanced Diagnostics

Periodic Reporting for period 1 - PiLOC (Next Generation Lab-On-a-Chip For Advanced Diagnostics)

Período documentado: 2021-04-01 hasta 2022-03-31

Microfluidics technology has revolutionised key applications like drug development, stem cell research, microbiological analysis, medical diagnosis, personalised medicine and chemical biology, just to name but a few. Microfluidic systems are always more present in chemistry and biochemistry labs, driving the development of new components and processes for the injection, mixing, pumping, and storing of fluids in the microchannels.
In this way, the progress of microfluidics technology has opened a completely new market for Lab-On-Chip systems (LOC), which are miniaturised devices intended to replicate what happens in a real lab, drastically improving cost efficiency, parallelization, ergonomics, diagnostic speed and sensitivity.
So, while thousands microfluidic channels are the highway where cells flow, in order to perform biomechanical operations a LOC must integrate pumps, electrodes, valves, and electronics.
Considering that the largest majority of microfluidic chips is made of glass or silicon due to the mature manufacturing process and excellent optical properties, surface stability, solvent compatibility, one question is puzzling the LOC industry: how to deal with the increased complexity of systems?
Unfortunately, while microfluidic channels can be easily manufactured with polymers, active components like actuators and valves integration is an unsolved issue, as their full integration with polymers would take place at processing temperature far beyond the melting point of polymers, and the only way to have such components in a LOC is by gluing them, which is totally unreproducible and leading to unreliable outcomes.
At Piemacs, a high tech startup company stemming from the pioneering research activities carried out at the EPFL’s Muralt’s lab, we propose a novel technology for the seamless integration of valves, pumps, injectors made with piezoelectric thin films onto polymer microfluidic chips, thus leading to the next generation low-cost and high performance LOC. This will allow monolithic fabrication of LOC using MEMS technology, benefiting from the advancements in MEMS manufacturing and the facilities available at EPFL. In the FET-OPEN BioWings the Consortium is developing a piezoelectric thin film to be used as an actuator material. As muscles, Piezoelectric thin films can produce force (or displacement) as function of applied electric filed.
The work performed include:
WP1: An analysis of the microfluidics industry has been carried out, to validate the competitive positioning of the Piloc technology with respect to the available alternatives.
The result has shown that the uniqueness of the original value proposition of the Piloc technology (i.e. seamless integration of actuators and valves into low-cost polymeric microfluidic channels) does not hold, particularly because there are other competing technologies with similar performance that already satisfy the customers’ needs of cheap and compact systems.
That’s why the analysis has been focused on the identification of another field of application where the Piloc technology could have a substantial market impact.
In this sense, we have identified the application of Piloc in high-frequency microfluidic channels for cells separation as the most promising scenario, at the same time validating the opportunity with a potential early customer (the company Acousort).
Following the identification of the potential value delivered by the Piloc technology in acoustophoresis cell separation approaches, which span blood-plasma, pathogen-plasma and exosomes-plasma separation, we have analysed the market potential and we have prepared a 5 years business plan to guide the further development of the technology.
Besides, given the context in which the activities have been carried out, a periodic Risk Management activity has been implemented, particularly to ensure the proper execution of the business and technical activities.

WP2: In terms of technology development, the activities of WP2 the core technology proposed in this proposal is successfully demonstrated. These results prove the validity of the proposed technology and can use as a ground to keep this technology a candidate for further studies. However, in order to take such a technology to the market and compete with existing technologies to fabricate microfluidic chips two major challenges must be addressed.
• Incompatibility with state-of-the-art micro fabrication process. Polymers are mainly considered a contaminant for many tools used in microfabrication.
• Choice of the polymer, current market of microfluidic chips is dominated by glass chips. Finding a polymer that can perform like a glass chip in terms of rigidity and reliability is proved that is not a trivial task.
After analyzing several candidate, SU8, was the polymer selected in this proposal for prove of the technology.
Microfluidics is a huge and expanding market, growing at one of the fastest rates in the biotech domain. Indeed, it is expected to move from the current around 15B€ to more than 40B€ by 2025, marking a 22.9% Compound Annual Growth Rate.
Precision medicine, advanced diagnostics (for instance, the fastest COVID-19 tests are based on microfluidic devices), point of care testing and utmost portability are the propelling factors of this market. Besides, there are several applications that are predicted to further boost the popularity of LOC, such as microfluidics-based 3D cell culture systems, organ-on-a-chip and novel drug delivery technologies.
The main bottleneck for a more widespread adoption of LOC in research and clinical practice is price constraint, which turns into the question for manufacturers of how to reduce the cost of goods sold (COGS) in view of large scale manufacturing volumes.
That’s why, decades after its inception, the microfluidics market has not reached tipping point.
With the PiLOC technology we foresee a possible reduction of the manufacturing cost down to few €cent per chip against current 2€-5€ for low-end disposable devices, and in the range of 5€-10€/chip for high-end systems which will replace best in class 500 €/chip silicon LOC. This result will be driven by:
• Replacement of Si-glass with low cost polymers, and integration of active components directly onto the microfluidic channels, avoiding the use of discrete valves, pumps, injectors and actuators.
• Manufacturing process replicating that of MEMS devices, leading to a reduction in the number of assembly steps, resulting in higher overall yields and a reduction in engineering costs (NRE). It also reduces the complexity of the manufacturing equipment, which lowers the investment cost (CAPEX) and reduces the effort to set-up processes.
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