Development of one-dimensional multipoint detection lifetime spectroscopy for monitoring single molecule binding kinetics within fluidic channels
Lead Research Organisation:
Imperial College London
Department Name: Chemistry
Abstract
There is a significant need across research and medical communities for highly sensitive spectroscopic techniques. Perhaps one of the most significant challenges facing physical and biological scientists is the accurate detection and identification of single molecules in free-solution environments for extended periods with high speed timing resolution. Currently such technologies do not exist. More specifically, we seek to drastically revamp conventional single molecule detection approaches by improving the performance in terms of timing, sensitivity, and spatial resolution via the integration of a novel multipoint detection spectrometer with nanofluidics. This technology will be used for tracking molecules in real time down the length of a fluidic channel. This tool will be used for studying molecular binding of Calmodulin (CaM) in the presence of calcium ions. This technology will function by flowing single molecules within a fluidic chip and monitoring changes in CaM conformations via fluorescence resonance energy transfer lifetimes in real time. This approach utilizes conventional semiconductor processing techniques to fabricate the fluidic devices and the detection technology builds on aspects of highly sensitive avalanche photodiode array detectors. We expect this work to have major impact and open up new possibilities for nano-analytical tools in the chemical and biological sciences. Importantly fundamental questions regarding different conformational states explored by a molecule, quantification of transition rates, and identification of transition pathways will be addressed.
Organisations
People |
ORCID iD |
Joshua Edel (Principal Investigator) |
Publications
Cecchini MP
(2011)
Flow-based autocorrelation studies for the detection and investigation of single-particle surface-enhanced resonance Raman spectroscopic events.
in Analytical chemistry
Crick CR
(2015)
Precise attoliter temperature control of nanopore sensors using a nanoplasmonic bullseye.
in Nano letters
Freedman K
(2016)
On-Demand Surface- and Tip-Enhanced Raman Spectroscopy Using Dielectrophoretic Trapping and Nanopore Sensing
in ACS Photonics
Ivanov AP
(2015)
On-demand delivery of single DNA molecules using nanopipets.
in ACS nano
Ivanov AP
(2014)
High precision fabrication and positioning of nanoelectrodes in a nanopore.
in ACS nano
Pitchford WH
(2015)
Synchronized optical and electronic detection of biomolecules using a low noise nanopore platform.
in ACS nano
Rutkowska A
(2015)
Electrodeposition and bipolar effects in metallized nanopores and their use in the detection of insulin.
in Analytical chemistry
Description | ERC Consolidator Grant |
Amount | € 1,970,000 (EUR) |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 08/2017 |
End | 09/2022 |
Description | Human Frontier Science Programme |
Amount | £644,000 (GBP) |
Funding ID | RGY0075 |
Organisation | Human Frontier Science Program (HFSP) |
Sector | Charity/Non Profit |
Country | France |
Start |
Description | Human Frontier Science Programme |
Amount | £644,000 (GBP) |
Funding ID | RGY0075 |
Organisation | Human Frontier Science Program (HFSP) |
Sector | Charity/Non Profit |
Country | France |
Start |