Label-free detection of proteins in optofluidic fibres
Lead Research Organisation:
University of Cambridge
Department Name: Physics
Abstract
CONTEXT
Proteins form the molecular machinery of life, and much of biological, biochemical and medical research revolves around the study of proteins and their interactions. We propose the development of a novel sensing platform that can study proteins and their interactions by continuously measuring their optical properties.
MOTIVATION, AIMS AND OBJECTIVES
Studying proteins in traditional optical microscopy is hindered by the proteins' low refractive index contrast, resulting in low-quality images. One solution commonly employed are fluorescent labels. However, this technique has its own set of drawbacks and affects the protein behaviour under study. In comparison, non-optical approaches such as electron microscopy offer excellent resolving power, but are unable to study proteins in their native environments. For the study of proteins, especially concerning their dynamics (aggregation, diffusion, shape changes), optical measurements are therefore the generally preferred method, and a new range of optical methods must be developed to fulfill this need.
RESEARCH METHODOLOGY AND TECHNIQUES
Photonic crystal fibres (PCFs) offer the ability to guide light based on interference effects arising from the light's wave-like properties. Owing to this propagation mechanism, a microfluidic central channel can be incorporated into them while retaining their guidance properties. Additionally, such hollow-core PCFs (HC-PCFs) present themselves as an extensible microfluidic sensing platform.[1] Several favourable characteristics[2] make HC-PCFs an attractive tool to be able to measure the optical characteristics of proteins. We will develop an integrated microfluidic setup using HC-PCFs to enable new kinds of optical studies to be performed on proteins.
APPLICATIONS OF THIS RESEARCH
Recent research identifies approximately 50 disorders as linked to protein aggregation, and their prevalence in the population is expected to counteract the continued increase in life expectancy that has occurred over the past decades.[3] The UK in general and Cambridge in particular have recently seen a push towards this area of research, such as with the Centre for Misfolding Diseases opening in 2018. Our research will continue to build on and extend these efforts further by diversifying the set of methods available to study proteins.
ALIGNMENT TO EPSRC RESEARCH THEMES
- Light matter interaction and optical phenomena
- We will gain new understanding of the light-matter interaction between proteins and light of different wavelength, confined in PCF of different geometry and light guidance
- Biophysics and soft matter physics
- Our work will add to the understanding of proteins as a fundamental building block of biology, in particular in confined spaces (i.e. with increased surface interactions, akin to compartementalisation)
- Optical devices and subsystems
- We explore new applications of HC-PCFs, including their further integration with microfluidic systems to aid automation and increase throughput
COLLABORATIONS
Collaborations for this project exist both within academia and to industry. Cambridge offers a strong biochemical research community that can supply protein samples. Already within the Sensor CDT, several such opportunities exist. In industry, Fluidic Analytics is a Cambridge-based startup that will be involved in this research. Collaborators at the Max Planck Institute for the Science of Light supply and design the HC-PCFs used for the project.
REFERENCES
[1] S. Unterkofler et al. "Microfluidic integration of photonic crystal fibers for online photochemical reaction analysis". In: Optics Letters (2012)
[2] Ana M. Cubillas et al. "Photonic crystal fibres for chemical sensing and photochemistry". In: Chem. Soc. Rev. (2013)
[3] Tuomas P. J. Knowles, Michele Vendruscolo, and Christopher M. Dobson. "The amyloid state and its association with protein misfolding diseases". In: Nature Reviews (2014)
Proteins form the molecular machinery of life, and much of biological, biochemical and medical research revolves around the study of proteins and their interactions. We propose the development of a novel sensing platform that can study proteins and their interactions by continuously measuring their optical properties.
MOTIVATION, AIMS AND OBJECTIVES
Studying proteins in traditional optical microscopy is hindered by the proteins' low refractive index contrast, resulting in low-quality images. One solution commonly employed are fluorescent labels. However, this technique has its own set of drawbacks and affects the protein behaviour under study. In comparison, non-optical approaches such as electron microscopy offer excellent resolving power, but are unable to study proteins in their native environments. For the study of proteins, especially concerning their dynamics (aggregation, diffusion, shape changes), optical measurements are therefore the generally preferred method, and a new range of optical methods must be developed to fulfill this need.
RESEARCH METHODOLOGY AND TECHNIQUES
Photonic crystal fibres (PCFs) offer the ability to guide light based on interference effects arising from the light's wave-like properties. Owing to this propagation mechanism, a microfluidic central channel can be incorporated into them while retaining their guidance properties. Additionally, such hollow-core PCFs (HC-PCFs) present themselves as an extensible microfluidic sensing platform.[1] Several favourable characteristics[2] make HC-PCFs an attractive tool to be able to measure the optical characteristics of proteins. We will develop an integrated microfluidic setup using HC-PCFs to enable new kinds of optical studies to be performed on proteins.
APPLICATIONS OF THIS RESEARCH
Recent research identifies approximately 50 disorders as linked to protein aggregation, and their prevalence in the population is expected to counteract the continued increase in life expectancy that has occurred over the past decades.[3] The UK in general and Cambridge in particular have recently seen a push towards this area of research, such as with the Centre for Misfolding Diseases opening in 2018. Our research will continue to build on and extend these efforts further by diversifying the set of methods available to study proteins.
ALIGNMENT TO EPSRC RESEARCH THEMES
- Light matter interaction and optical phenomena
- We will gain new understanding of the light-matter interaction between proteins and light of different wavelength, confined in PCF of different geometry and light guidance
- Biophysics and soft matter physics
- Our work will add to the understanding of proteins as a fundamental building block of biology, in particular in confined spaces (i.e. with increased surface interactions, akin to compartementalisation)
- Optical devices and subsystems
- We explore new applications of HC-PCFs, including their further integration with microfluidic systems to aid automation and increase throughput
COLLABORATIONS
Collaborations for this project exist both within academia and to industry. Cambridge offers a strong biochemical research community that can supply protein samples. Already within the Sensor CDT, several such opportunities exist. In industry, Fluidic Analytics is a Cambridge-based startup that will be involved in this research. Collaborators at the Max Planck Institute for the Science of Light supply and design the HC-PCFs used for the project.
REFERENCES
[1] S. Unterkofler et al. "Microfluidic integration of photonic crystal fibers for online photochemical reaction analysis". In: Optics Letters (2012)
[2] Ana M. Cubillas et al. "Photonic crystal fibres for chemical sensing and photochemistry". In: Chem. Soc. Rev. (2013)
[3] Tuomas P. J. Knowles, Michele Vendruscolo, and Christopher M. Dobson. "The amyloid state and its association with protein misfolding diseases". In: Nature Reviews (2014)
