* Monolithically integrated interferometric biochiPs for label-free earlY deTection of Human dIseAses
PYTHIA project aims at the development of an innovative optoelectronic biochip for the early diagnosis of human diseases through label-free multi-analyte detection. These biochips are envisioned to "prophesise" potential predisposition to, or diagnose the early onset of human diseases, paving the way for advances in personalised health care. The principle of operation of the PYTHIA biochip is based on Broad-Band Mach-Zehnder Interferometry which improves the sensing capabilities over other main stream optical detection schemes. The PYTHIA biochip is built around an optoelectronic transducer consisting of a VIS-NIR light source and an interferometric waveguide all monolithically integrated on a single Si chip. The integration of all passive and active optical components on the same Si chip achieves the highest miniaturization level and overcomes the limitations of all optical transducers developed so far. Its breakthrough design makes use of conventional microchip technologies while circumventing common manufacturability issues. The final goal of the biochip is to enable the medical community to simultaneously diagnose a variety of diseases.
The transducer's ultimate integration level allows for the development of arrays consisting of individually functionalized interferometers coupled to their excitation source, and converging to a common detector for multiplexed operation. Encapsulation at wafer scale with a microfluidic system allows for the easy delivery of samples, while boarding on a disposable cartridge ensures the facile contact with the measuring apparatus.
The final system will be capable of simultaneous multi-analyte detection, real-time reaction monitoring and data processing, requiring minimal sample volumes and a few minutes of operation.
The system is completed by a user-friendly software for ease-of-use that does not require the presence of highly trained personnel and can be applied in any size diagnostic centre or even a privately owned practice. The final system will have the ability to be tailored to diverse diagnostic applications and patient or population genetic profiles.
The great potential and analytical breakthroughs of the proposed biochip will be demonstrated through its use in:
- Prostate cancer, a frequently occurring disease severely burdening health care systems.
- MEN2, a medical condition, linked to an inherited faulty gene (RET), demonstrating the ability of the biochip for efficient predisposition screening of population-specific genetic profiles.
- Retinitis Pigmentosa (inherited diseases group causing retinal degeneration and vision loss) demonstrating substantial downgrading of the diagnostics costs of genetically complex diseases.
Policy Context
The development of miniaturised and more powerful analytical and diagnostic tools for the early detection of diseases & for point-of-care monitoring systems is of very high priority for the whole healthcare sector.
Photonic biosensors are considered as very promising solutions towards this objective. Despite their attractive attributes, the existing optical biosensors are burdened with the need of external optical components and the final systems are bulky regardless of the miniaturisation level of the biosensors themselves.
For the fabrication of the next generation of compact, portable, cost-efficient biosensors which will allow for the label-free, real-time detection of biomolecules (like proteins and DNA strands) at very low concentrations in small-volume samples, "smarter" designs are direly required. These designs should also result into biosensing devices able to be mass produced and used in any size clinical centre or even private practice by non-specialised personnel.
Technology solution
The principle of operation of the PYTHIA biosensor device is significantly different from the existing detection approaches and is based on broad-band Mach-Zehnder interferometry (BBMZI). The basic sensor scheme consists of a VIS-NIR light source and a waveguide monolithically fabricated on a silicon wafer, while its principle of operation is the spectroscopic interference due to the optical path difference originating by biochemical events. The signal recording will be realised either via an also monolithically fabricated photodetector or via an external spectrophotometer.
The integrated nature of the basic biosensor scheme allows for the development of arrays tailored to specific diagnostic applications. Each biosensor array will be comprised of individually functionalised light source/optical waveguide series coupled to a single detector for multiplexing operation. Encapsulation with an appropriately designed microfluidic system will allow for the easy delivery of the samples to be analysed and ensure the facile contact with the external low-noise electronic components. The encapsulated array will be fixed on a cartridge, ready to be manually inserted to its final position in the housing, where it will be directly connected to the optical and electrical interconnects. The biochip, controlled by accompanying user-friendly software, will be capable of simultaneous multi-analyte detection (e.g. mutations of specific genes), and real-time monitoring and processing, with a detection duration that will not exceed a few minutes with minimal blood sample volumes or specimens.
Technology choice: Proprietary technologyMain results, benefits and impacts
Vision
The PYTHIA project aims at the development of a novel optoelectronic transducer based on broad-band Mach-Zehnder Interferometry (BB-MZI), suitable for wafer scale fabrication, functionalisation and encapsulation and its application to the early diagnosis of human diseases through the label-free, multi-analyte detection of gene mutations and proteins.
The PYTHIA biochip is the only device in the world where all active and passive optical components (light source, waveguides, photodetector) are monolithically integrated all in the same Si chip, and fabricated by standard silicon technologies only.
The electro-optical bio-transducer, addresses all key issues of existing optical biochips: miniaturisation, ultimate integration level, improved sensitivity and detection limits, repeatability, and adaptability to various diagnostic schemes (genomics and proteomics).
The PYTHIA biochip becomes the only truly integrated, fully-compact, all-Si optical biosensor that can be readily implemented to mass-production.
The biochip, controlled by accompanying user-friendly software, will be capable of simultaneous multi-analyte and real-time detection, with an assay duration that will not exceed a few minutes with minimal blood sample volumes or specimens.
Results
The PYTHIA optoelectronic transducer consists of a VISNIR light source and a waveguide monolithically fabricated on a Si wafer and patterned in two arms. Its principle of operation is the spectroscopic interference due to the optical path difference between the reference and properly functionalised sensing arm originating from biochemical events. The signal recording is realised either via an also monolithically fabricated photodetector or via an external spectrophotometer.
The basic biosensor scheme allows for the development of arrays consisting of individually functionalised light source/optical waveguide series coupled to a single detector for multiplexing operation.
Wafer-scale encapsulation along with an appropriately designed microfluidic system allow for the easy delivery of the samples and ensure the facile contact with the external low-noise electronic components. The encapsulated array is fixed on a cartridge ready to be manually inserted to its final position in the housing.
The electrical and optical characterisation of the first batch of optoelectronic transducers provided a solid confirmation of the BB-MZI concept and useful information for the design optimisation of the biosensor chips. The transducers were functionalised and encapsulated with a microfluidic cell to be possible to evaluate them in real conditions. For the Biotin- Streptavidin model assay, the detection of streptavidin in the picomolar range was easily demonstrated, which is comparable with the state of the art values for labelfree biosensors.
The progress in the design and fabrication of the biochip along with the preliminary results obtained so far are convincing that the PYTHIA biochip and measuring apparatus will be able to diagnose diseases at an early stage, determine whether one will suffer from hereditary diseases and provide head-up warnings for one's well-being.
Return on investment
Return on investment: Not applicable / Not availableLessons learnt
This field will be completed by the submitter when the lessons learnt have been identified and understood.
Scope: Cross-border, International