Particle Filtration and Accumulation by Solute-driven Transport (FAST) for bio-analysis in microfluidic devices

Lead Research Organisation: Loughborough University
Department Name: Chemical Engineering

Abstract

The outcomes of many health interventions critically depend on the ability to identify the disease in a timely manner so the most appropriate therapy can be chosen promptly. Consequently, there is an immediate and growing need to develop healthcare technologies for rapid and accurate detection of bio-markers, associated with specific diseases, and/or disease causative agents, such as pathogenic microorganisms. Microfluidics and lab-on-a-chip technology offer a huge potential for the development of next generation fast and ultra-sensitive bio-analytical devices for diagnostic and therapeutic applications.

Particle handling operations - including separation, filtration, concentration, trapping and sorting - are ubiquitous in microfluidic diagnostic technologies and can ultimately dictate the speed, accuracy and selectivity of testing devices. An ideal particle handling technique would be fast (high-throughput), selective (i.e. targeting only the particles of interest), easy to integrate into a multifunctional microfluidic device and, most importantly, not reliant on the use of external fields. This proposal aims to introduce an innovative particle manipulation technique to address all these requirements. This research will also demonstrate the proof-of-concept for using this technique to develop fast and sensitive diagnostic testing devices.

Rapid filtration, trapping and accumulation of target particles within the cavities of micro-structured surfaces will be achieved in continuous flow settings by harvesting the chemical energy associated with salt contrast generated by parallel multi-component flows. The mechanisms governing the particle dynamics will be investigated through a combination of experimental and numerical techniques. The dependence of trapping and concentration efficiency on particle properties (especially size and surface chemistry) will be elucidated. The output of this study will be an optimally-designed microfluidic platform, through which two in-vitro diagnostic devices will be developed. One device will enable the rapid filtration of cell-like particles (e.g. liposomes) based on their lipid membrane composition which is an important indicator of a cell's state of health. This assay will offer new opportunities for early detection of drug induced cell death and rapid drug pharmacokinetics screening. Another device will enable the fast and ultrasensitive detection of a biomarker indicative of pathological conditions, including atherosclerosis, pancreatitis and some forms of cancers. Synthetic bio-compatible particles will be incubated in a sample solution where the specific interaction with the disease biomarkers will cause i) the fluorescent signal emission from the particle and ii) a change in particle surface chemistry. The latter effect is intended to enable the conversion of the chemical energy - stored in the form of salt contrast - into particle motion. As a result, the biomarker-activated fluorescent particles will be rapidly trapped and accumulated within target regions of the device whereas the non-fluorescent particles will remain unaffected by the presence of the salt. This will enable a massive signal amplification for the diagnostic assay and, consequently, a fast and accurate detection of biomarker concentration in the analysed sample.

In summary, this research will lay the foundation for the development of a new family of low-cost, portable bio-analytical devices based on particle filtration and accumulation by solute-driven transport (FAST) for diagnostic and therapeutic applications. These innovative and highly-sensitive diagnostic tools will enable clinicians to perform rapid and accurate diagnosis and, hence, make timely and informed clinical treatment decisions which are more likely to lead to successful health outcomes.

Planned Impact

The project aligns with the EPSRC's prosperity outcomes in Health and Productivity and has potential for significant impacts at different levels. Many chronic disorders, including cardiovascular and metabolic diseases, dementia and cancers, may be asymptomatic until the latter stages of the disease, at which point the chances of successful treatments are reduced and the cost of health intervention increased. It is predicted that in UK every year around 50,000 individuals receive a late diagnosis of cancer, this resulting in ca. £210 million in extra cost for the NHS [Birtwistle et al, Saving lives, averting costs. Cancer Res. UK, 2014]. These numbers increase rapidly when other forms of asymptomatic diseases are accounted for.

Societal and economic impact will be realised through improved diagnosis and treatment opportunities offered by the development of a new paradigm for bioanalysis in microfluidic systems. By establishing a new particle manipulation strategy and introducing a proof-of-principle microfluidic platform for bio-analysis, this research will support the development, over the next 10-15 years, of novel low-cost bio-analytical microsystems with better sensitivity, shorter analysis time and higher throughput. Providing clinicians with such new bio-analytical tools will enable them to make more accurate diagnoses at earlier stages in the disease's course even in out-of-hospital settings (e.g. GP's surgery or patient's home). Consequently, patients - especially elderly individuals, those with asymptomatic and/or chronic diseases and/or limited mobility - will benefit from earlier diagnoses, improved treatment and, hence, higher chances of better health outcomes. Project outcomes and follow-up research activities, detailed in the "Pathways to Impact", will contribute towards the UK life science sector's ambition to radically transform the paradigm of healthcare delivery over the next two decades by shifting from a healthcare system providing costly treatments in hospitals for late-stage patients to a more economically sustainable system based on low-cost point-of-need early diagnoses, prevention and rapid intervention.

This research has further potential for economic impact by contributing to innovation in UK industry leading to commercial realisation of innovative bio-analytical and in-vitro diagnostics technologies - a market in the UK worth ca. £2.6 billion in 2014 and expected to reach £3.4 billion in 2020. End users of this research include enterprises in the UK focusing on manufacture of portable microfluidic systems for applications in chemistry, biology and medicine. Providing industry manufacturers with innovative methods for particle manipulation and bio-analysis will offer tremendous opportunities for design and commercialisation of a new family of microfluidic system products for bio-analysis, diagnostics, drug screening and drug delivery. This will enrich the product portfolio of these end users, enhance their global competitiveness and allow them to exploit new and rapidly expanding markets, such as those emerging from a growing population of elderly individuals with complex health needs. Examples of innovative products may include point-of-need diagnostic chips, microfluidic systems for cell filtration/analysis and microdevices for drug-cell interaction studies and drug development.

Finally, it is well recognised that interdisciplinary research has a critical role in bridging the gap between industry and academia - especially in the field of microfluidics and healthcare technologies. By bringing together project partners and advisors with expertise ranging from colloid and interface science to biochemistry, from the physics of liquids to healthcare and diagnostics, research staff at PhD and post-doctoral levels will be trained in a highly interdisciplinary environment and equipped with technical and transferable skills required to become future research leaders in UK industry and academia.

Publications

10 25 50
 
Description We discovered a novel physical mechanism that enables the rapid accumulation and trapping of small (sub-micron) particles within dead-end structures, such as close-ended pores and microchannels.

Biological fluids are full of particles and being able to trap and release them is a key underpinning capability for several technological applications, including the analysis of body fluids such as blood and saliva. Diagnostics - such as virus detection - can be limited by the number of biological particles intercepted by the diagnostic instrument so the ability to concentrate particles in one area could lead to more accurate detection and as a result, earlier medical interventions. Current methods to concentrate particles do exist, but they involve lab-based technology such as centrifuges and cannot be used to trap particles inside the body.

We identified a new mechanism that can be used to trap particles in both living and artificial biological systems.
We designed and manufactured a bespoke microchannel device, just a few times thicker than a human hair, containing microcavities and openings that can be flooded with salty water streams. We demonstrated that slight difference in the salinity level [saltiness] of the water streams is enough to keep the particles stationary and the salt within the microcavities acts similar to a magnet, drawing the particles down into the dead-end regions. This process can be reversed, which has huge implications for applications that require the trapping and later release of particles, for example, the time-controlled delivery of multiple drugs into dead-end regions.
Exploitation Route Too early to say (the award is still active)
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description CR Barber Trust Fund travel bursary scheme
Amount £100 (GBP)
Organisation Institute of Physics (IOP) 
Sector Learned Society
Country United Kingdom
Start 10/2019 
End 10/2019
 
Description Integrated atomic force and confocal fluorescence lifetime imaging microscope with fibre-coupled infrared detector for materials research
Amount £817,063 (GBP)
Funding ID EP/T006412/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 12/2021
 
Description SCI Messel Travel Bursary 2020
Amount £500 (GBP)
Organisation Society of Chemical Industry 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2020 
End 02/2021
 
Description Travel Grants for PhD Students and Early Career Scientists, Faraday Division, Royal Society of Chemistry
Amount £800 (GBP)
Funding ID T19-3341 
Organisation Royal Society of Chemistry 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 11/2019
 
Title Supplementary Information Files for Reversible trapping of colloids in microgrooved channels via diffusiophoresis under steady-state solute gradients 
Description Supplementary Information Files for Reversible trapping of colloids in microgrooved channels via diffusiophoresis under steady-state solute gradients
The controlled transport of colloids in dead-end structures is a key capability that can enable a wide range of applications, such as bio-chemical analysis, drug delivery and underground oil recovery. This letter presents a new trapping mechanism that allows the fast (i.e., within a few minutes) and reversible accumulation of sub-micron particles within dead-end micro-grooves by means of parallel streams with different salinity level. For the first time, particle focusing in dead-end structures is achieved under steady-state gradients. Confocal microscopy analysis and numerical investigations show that the particles are trapped at a flow recirculation region within the grooves due to a combination of diffusiophoresis transport and hydrodynamic effects. Counterintuitively, the particle velocity at the focusing point is not vanishing and, hence, the particles are continuously transported in and out of the focusing point. The accumulation process is also reversible and one can cyclically trap and release the colloids by controlling the salt concentration of the streams via a flow switching valve. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://repository.lboro.ac.uk/articles/dataset/Supplementary_Information_Files_for_Reversible_trapp...
 
Title Supplementary Information Files for Reversible trapping of colloids in microgrooved channels via diffusiophoresis under steady-state solute gradients 
Description Supplementary Information Files for Reversible trapping of colloids in microgrooved channels via diffusiophoresis under steady-state solute gradients
The controlled transport of colloids in dead-end structures is a key capability that can enable a wide range of applications, such as bio-chemical analysis, drug delivery and underground oil recovery. This letter presents a new trapping mechanism that allows the fast (i.e., within a few minutes) and reversible accumulation of sub-micron particles within dead-end micro-grooves by means of parallel streams with different salinity level. For the first time, particle focusing in dead-end structures is achieved under steady-state gradients. Confocal microscopy analysis and numerical investigations show that the particles are trapped at a flow recirculation region within the grooves due to a combination of diffusiophoresis transport and hydrodynamic effects. Counterintuitively, the particle velocity at the focusing point is not vanishing and, hence, the particles are continuously transported in and out of the focusing point. The accumulation process is also reversible and one can cyclically trap and release the colloids by controlling the salt concentration of the streams via a flow switching valve. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
URL https://repository.lboro.ac.uk/articles/dataset/Supplementary_Information_Files_for_Reversible_trapp...
 
Description Solute-driven Transport of Nanoparticles in Confined Geometries 
Organisation Claude Bernard University Lyon 1 (UCBL)
Country France 
Sector Academic/University 
PI Contribution My research group has developed the idea and design the research programme for this joint collaborative research. A PhD student of my group has also been working full time on this collaborative research project. My group has also performed the experimental and numerical work for this collaborative research.
Collaborator Contribution My collaborators at the University Claude Bernard Lyon 1 has contributed to this collaboration through free-of-charge access to their laboratories and facilities in France, provision of bespoke microdevices manufactured in their cleanroom facilities as well as through their expertise on micro/nano-fluidics, liquid and interface dynamics, solute-driven flow and particle transport. They have also been actively contributing to the experimental and theoretical research work undertaken during this collaboration.
Impact Oral Presentation at 72nd Annual Meeting of the APS Division of Fluid Dynamics, November 2019, Seattle (USA) Oral Presentation at 32nd Conference of the European Colloid and Interface Society, Ljubljana (Slovenia) September 2019 Poster Presentation at "Applications of Diffusiophoresis in Drying, Freezing and Flowing Colloidal Suspensions", CECAM Workshop, Lausanne (Switzerland) November 2019 Oral Presentation at 2nd Annual Early Career Colloid Meeting ECCo 2019
Start Year 2018
 
Description Group and Project Website and Social Media Activity 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I have set up a website to advertise my group's research activities, including those associated to this project. The website (www.particlemicrofluidics.com) describes the type of research undertaken by my team as well as report the engagement and dissemination activities undertaken by my team members. I also advertise such activities on my Twitter media account. My social media account and group website are visited by other academics and industry representatives, scientific journalists and undergraduate and postgraduate students. Outcomes of this engagement activities includes invited interviews on media for experts comments and the establishment of new contacts with potential industrial partners as well as PhD student canditate willing to engage with this research project.
Year(s) Of Engagement Activity 2019
URL http://www.particlemicrofluidics.com
 
Description Press Release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Press release by Loughborough University highlighting the research outcomes of the project and their implications for future technology development.
Link: https://www.lboro.ac.uk/media-centre/press-releases/2020/december/salt-bioengineering-new-paper/

The press released was covered by national and international news outlet including the scientific magazine, The Engineer
Link: https://www.theengineer.co.uk/study-finds-salt-could-revolutionise-bio-analysis/

and the science website phys.org
Link: https://phys.org/news/2020-12-experts-mechanism-submicron-particles-minutes.html
Year(s) Of Engagement Activity 2020
URL https://www.lboro.ac.uk/media-centre/press-releases/2020/december/salt-bioengineering-new-paper/