PLATFORM: Exploring the Potential of Compartmentalisation for Selections and Ultra-high-throughput Screening
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
We have assembled a team of scientists from Cambridge, France, Israel and the USA to develop the use of microdroplets in microfluidics as microreactors. These droplets (which measure a few millionth of a metre across) are equivalent to very small reaction flasks in which chemical or biological reactions can be performed on a minute scale. The droplets are made, manipulated and analysed in microfluidic systems, consisting of networks of microscopic channels through which the droplets flow in a stream of oil. It will be possible to make and analyse millions of droplets in an hour.Cambridge has pioneered the use of microdroplets for biological applications. Our current ambition is to maintain our lead in the area, while at the same time expanding the range of experiments that can be performed, and showing that the methodology has applications across biology and into chemistry and material sciences. The Platform grant will be used to fund our expanding research in this area. It will provide greater flexibility in our existing research in several ways, for example by providing extra funds for experienced researchers to spend more time with us, or to fund scientists who come with fellowships but no extra money to support their science. In particular it will make it easier for us to send our researchers to learn techniques in collaborating laboratories in France, Israel and the USA. It will also allow us to be adventurous with our science and start exploratory new projects, especially ones that cross normal scientific boundaries.
Organisations
Publications
Abalde-Cela S
(2011)
Microdroplet fabrication of silver-agarose nanocomposite beads for SERS optical accumulation
in Soft Matter
Bai Y
(2010)
A double droplet trap system for studying mass transport across a droplet-droplet interface.
in Lab on a chip
Casadevall I Solvas X
(2011)
High-throughput age synchronisation of Caenorhabditis elegans.
in Chemical communications (Cambridge, England)
Casadevall I Solvas X
(2012)
Microfluidic evaporator for on-chip sample concentration.
in Lab on a chip
Casadevall I Solvas X
(2011)
Fluorescence detection methods for microfluidic droplet platforms.
in Journal of visualized experiments : JoVE
Courtois F
(2009)
Controlling the retention of small molecules in emulsion microdroplets for use in cell-based assays.
in Analytical chemistry
Courtois F
(2009)
Towards biological experimentation in microfludic microdroplets
in La Houille Blanche
Courtois F
(2008)
An integrated device for monitoring time-dependent in vitro expression from single genes in picolitre droplets.
in Chembiochem : a European journal of chemical biology
Draper MC
(2012)
Compartmentalization of electrophoretically separated analytes in a multiphase microfluidic platform.
in Analytical chemistry
| Description | The platform grant has proved invaluable in providing underpinning funding for our microdroplets group and helped it develop into two major interdisciplinary research groups and a spin out company. The platform grant was used to fund science across the spectrum from device design and fabrication through to a range of diverse applications. Specifically we developed novel traps for holding droplets, a method for surface-induced droplet fusion, a way to selectively separate and de-emulsify droplets (patented). A key focus has been the detection of droplet contents by mass spectrometry (patented). This is of potentially significant commercial interest. We also developed novel fluorous surfactants. This has proved particularly important. Using funding from the Platform grant we used microdroplets in a range of application areas, including: in vitro protein expression from single genes; quantitative enzymatic and cell based assays; and in developing methodology to follow reactions on a sub millisecond timescale. Ongoing projects include establishing methods to screen for enzymatic ethanol production in microdroplets; to grow yeast in droplets to assess selectivity effects of enzyme inihbitors from growth curve measurements; and to grow mammalian cells in microdroplets, to facilitate transfection experiments. Funding from the Platform grant has been pivotal in underpinning existing collaborations, including a collaborative study with Prof Dan Tawfik (Weizman, Israel) on quantitative comparison of bulk emulsion and microfluidic droplet protocols. It has also been especially useful for catalyzing the development of new collaborations. These include: (1) on stem cells with Prof Fiona Watt (Centre for Stem Cell Research) to study single cell signalling and cell fate in cells on defined supports. We prepared monodisperse gel beads with skin stem cells compartmentalized inside that are suitable for cell growth and can be implanted in mice to study the formation hair follicles. (2) On algal biofuels with Prof Alison Smith (Plant Sciences). We have developed methodology to culture algae in droplets and simultaneously measure their chlorophyll and lipid content. This will enable screening libraries of modified algae thousands of times faster than present methods. (3) On enzyme expression with Prof John Oakeshott (CSIRO), and Profs Nick Dixon and Chris Easton (ANU, Australia). (4) On the fabrication of novel SERS active nanocomposites with Prof Luis Liz-Martin, (Vigo, Spain). The Platform funding has been used to extend contracts, provide short term support, provide exploratory funding, and to develop new collaborations. It played a pivotal role in firmly establishing microdroplet technology at Cambridge. |
| Exploitation Route | Microdroplet technology is a new platform technology that has potential applications in many areas of experimental science, most obviously molecular and cell biology, but also chemistry and material science. We have created a University spin out company (Sphere Fluidics http://www.spherefluidics.eu/) that has already been involved in collaborations with two US companies. We have used every opportunity to promote the science in academia and industry. We have also provided advice and training to companies interested in the technology. For example, when Kodak were interested in exploring the use of PDMS for device fabrication for ultrafast droplet formation, we provided training in all aspects of PDMS-based droplet microfluidics. Prototypes were made in the university lab by a Kodak employee and the expertise transferred to Kodak. We have given several lectures for the European Microfluidics Consortium. The Department of Chemistry has continued to invest in this area with the recent appointment of Dr Toumas Knowles to a lectureship. The PIs continue to expand their interests in this area. Most notably Dr Huck (now Professor) recently moved to take up a Chair in Nijmegen to focus exclusively on microdroplets. We have been successful in obtaining significant follow on funds for our microdroplet research, to maintain the momentum created from the Platform Grant funding. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | They stimulated further research which led to the creation of several spinouts |
| First Year Of Impact | 2010 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BBSRC Studentship |
| Amount | £70,000 (GBP) |
| Funding ID | BB/I016589/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2011 |
| End | 09/2015 |
| Description | ERC Advanced Grant |
| Amount | £1,890,000 (GBP) |
| Funding ID | 246812 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 04/2010 |
| End | 03/2015 |
| Description | European Research Council |
| Amount | £135,965 (GBP) |
| Funding ID | PIEF-GA-2009-255262 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 05/2010 |
| End | 04/2012 |
| Description | European Research Council |
| Amount | £135,965 (GBP) |
| Funding ID | PEF-GA-2010-276275 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 06/2011 |
| End | 05/2013 |
| Description | Follow-on-fund (from Impact Acceleration Account) |
| Amount | £59,814 (GBP) |
| Funding ID | EP/K503757/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2013 |
| End | 10/2014 |
| Description | MC-IIF - International Incoming Fellowships (IIF) |
| Amount | € 174,240 (EUR) |
| Funding ID | 255500 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 06/2010 |
| End | 05/2012 |
| Description | Partnership Development Award (from Impact Acceleration Account) |
| Amount | £44,588 (GBP) |
| Funding ID | EP/K503757/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2014 |
| End | 10/2015 |
| Description | Standard Research |
| Amount | £1,067,243 (GBP) |
| Funding ID | EP/H046593/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2010 |
| End | 04/2014 |
| Title | IONISATION MASS SPECTROMETRY |
| Description | Systems that employ microdroplets are used in embodiments for Microdroplet Electrospray Ionisation Mass Spectrometry (ESI MS). Thus, a method of detecting an analyte includes providing an oil composition comprising oil and an aqueous microdroplet comprising the analyte, the oil composition comprising a surfactant to stabilise the aqueous microdroplet in the oil composition; and performing ionisation mass spectrometry analysis of the oil composition. |
| IP Reference | US2013187040 |
| Protection | Patent application published |
| Year Protection Granted | 2013 |
| Licensed | Yes |
| Impact | None |
| Title | MICROFLUIDIC DEVICES |
| Description | We describe a method of layer-by-layer deposition of a plurality of layers of material onto the wall or walls of a channel of a microfluidic device, the method comprising: loading a tube with a series of segments of solution, a said segment of solution bearing a material to be deposited; coupling said tube to said microfluidic device; and injecting said segments of solution into said microfluidic device such that said segments of solution pass, in turn, through said channel depositing successive layers of material to perform said layer-by-layer deposition onto said wall or walls of said channel. Embodiments of the methods are particularly useful for automated surface modification of plastic, for example PDMS (Poly(dimethylsiloxane)), microchannels. We also describe methods and apparatus for forming double-emulsions. |
| IP Reference | US2012168010 |
| Protection | Patent application published |
| Year Protection Granted | 2012 |
| Licensed | Yes |
| Impact | None |
| Title | MICROFLUIDIC SYSTEMS |
| Description | This invention relates to microfluidic systems and more particularly to methods and apparatus for accessing the contents of micro droplets (114) in an emulsion stream. A method of accessing the contents of a droplet (114) of an emulsion in a microfluidic system, the method comprising: flowing the emulsion alongside a continuous, non-emulsive stream of second fluid (118) to provide an interface (120) between said emulsion and said stream of second fluid (118); and in embodiments applying one or both of an electric (112a, 112b) and magnetic field across said interface (120) to alter a trajectory of a said droplet (114) of said emulsion to cause said droplet to coalesce with said stream of second fluid (118); and accessing said contents of said droplet (114) in said second stream (118). |
| IP Reference | US2012091004 |
| Protection | Patent application published |
| Year Protection Granted | 2012 |
| Licensed | Yes |
| Impact | None |
| Title | Microdroplet emulsion system |
| Description | Methods and systems for providing chemical and/or biological materials in a quantised form. The method comprises: preparing an emulsion comprising a plurality of microdroplets each holding a controlled amount of the material, storing the chemical or biological material in the microdroplets in the emulsion, transferring a portion of the emulsion microdroplets to a container for transportation, transporting the container to a user of the material, wherein the user receives the material in a quantised form in the microdroplets of the emulsion and de-emulsifying the received microdroplets containing the material in quantised form to extract the material for subsequent use. There is also apparatus for handling such emulsions. |
| IP Reference | GB2482911 |
| Protection | Patent application published |
| Year Protection Granted | 2012 |
| Licensed | Yes |
| Impact | None |
| Company Name | Sphere Fluidics Limited |
| Description | Sphere Fluidics Limited is an established Life Sciences company which has developed unique products for use in single cell analysis and characterisation and provides collaborative Research and Development services in this area. |
| Year Established | 2010 |
| Impact | Sphere Fluidics is one of the very few teams in the world with expertise in single cell analysis and pico droplet technology. The company has leading-edge, patented technology and proprietary know-how enables analysis and detection of single cells and their biomolecules. Sphere Fluidics has extensive management experience in successfully commercialising innovative science and engineering. Its expertise in new science with key applications has particular impact for novel biopharmaceutical and biosimilar discovery. Sphere Fluidics' novel process for single cell analysis and characterisation provides significant saving of time, resource and money compared to conventional workflows. |
| Website | http://www.spherefluidics.eu/index.php |
| Description | Droplet Reactors with Catalytic Interfaces: An Active Fluorous Phase for Segmented-Flow Microfluidic Reactions |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Shared research output with other research scientists in the field Interest in our research at the Microdroplets group in the Univesity of Cambridge, UK |
| Year(s) Of Engagement Activity | 2009 |