Adaptive optics for three-dimensional microscopy and photonic engineering
Lead Research Organisation:
University of Oxford
Department Name: Engineering Science
Abstract
Light is a versatile tool for imaging and engineering on microscopic scales. Optical microscopes use focused light so that we can view specimens with high resolution. These microscopes are widely used in the life sciences to permit the visualisation of cellular structures and sub-cellular processes. However, the resolution of an optical microscope is often adversely affected by the very presence of the specimen it images. Variations in the optical properties of the specimen introduce optical distortions, known as aberrations, that compromise image quality. This is a particular problem when imaging deep into thick specimens such as skin or brain tissue. Ultimately, the aberrations restrict the amount of the specimen that can be observed by the microscope, the depth often being limited to a few cellular layers near the surface. This is a serious limitation if one wants to observe cells and their processes in their natural environment, rather than on a microscope slide. I am developing microscopes that will remove the problematic aberrations and enable high resolution imaging deep in specimens.Focused light also has other less well-known uses. It can be used to initiate chemical reactions that create polymer or metal building blocks for fabrication on the sub-micrometre scale. These blocks, with sizes as small as a few tens of nanometers, can be built into structures in a block-by-block fashion. Alternatively, larger blocks of material can be sculpted into shape using the high intensities of focused lasers. These optical methods of fabrication show potential for use in the manufacture of nanotechnological devices. When manufacturing such devices, the laser must be focused through parts of the pre-fabricated structure. The greater the overall size and complexity of the structures, the more the effects of aberrations degrade the precision of the fabrication system. My research centres on the use of advanced techniques to measure and correct such distortions, restoring the accuracy of these optical systems.Traditional optical systems consist mainly of static elements, e.g. lenses for focusing, mirrors for reflecting and scanning, and prisms for separating different wavelengths. However, in the systems I use the aberrations are changing constantly. Therefore they require an adaptive method of correction in which the aberrations are dynamically compensated. These adaptive optics techniques were originally developed for astronomical and military purposes, for stabilising and de-blurring telescope images of stars and satellites. Such images are affected by the aberrations introduced by turbulence in the Earth's atmosphere. The most obvious manifestation of this is the twinkling of stars seen by the naked eye. Recent technological developments, such as compact and affordable deformable mirrors for compensating the optical distortions, mean that this technology is now being developed for more down-to-Earth reasons. This has opened up the possibility of using adaptive optics in smaller scale applications.In conjunction with researchers in Japan and Australia, I will develop adaptive optical fabrication systems that will be able to produce complex micrometre-scale structures with greater accuracy than was previously possible. With biologists in the University of Oxford, I will use adaptive optics to increase the capabilities of microscopes in imaging deep into thick specimens. This will enable biologists to learn more about the processes that occur within cells and the development of organisms. The aberration correction technology will also have use in other areas such as medical imaging, optical communications and astronomy.
People |
ORCID iD |
| Martin Booth (Principal Investigator) |
Publications
Booth M
(2014)
Adaptive optical microscopy: the ongoing quest for a perfect image
in Light: Science & Applications
Booth MJ
(2010)
Full spectrum filterless fluorescence microscopy.
in Journal of microscopy
Botcherby EJ
(2013)
Fast measurement of sarcomere length and cell orientation in Langendorff-perfused hearts using remote focusing microscopy.
in Circulation research
Botcherby EJ
(2009)
Real-time slit scanning microscopy in the meridional plane.
in Optics letters
Botcherby EJ
(2012)
Aberration-free three-dimensional multiphoton imaging of neuronal activity at kHz rates.
in Proceedings of the National Academy of Sciences of the United States of America
Botcherby EJ
(2008)
Real-time extended depth of field microscopy.
in Optics express
Carbone G
(2011)
Uniform Lying Helix Alignment on Periodic Surface Relief Structure Generated via Laser Scanning Lithography
in Molecular Crystals and Liquid Crystals
Corbett AD
(2014)
Quantifying distortions in two-photon remote focussing microscope images using a volumetric calibration specimen.
in Frontiers in physiology
Cumming BP
(2011)
Adaptive aberration compensation for three-dimensional micro-fabrication of photonic crystals in lithium niobate.
in Optics express
Débarre D
(2008)
Adaptive optics for structured illumination microscopy.
in Optics express
Débarre D
(2009)
Image-based adaptive optics for two-photon microscopy.
in Optics letters
Gould TJ
(2012)
Adaptive optics enables 3D STED microscopy in aberrating specimens.
in Optics express
Gould TJ
(2013)
Auto-aligning stimulated emission depletion microscope using adaptive optics.
in Optics letters
Huang L
(2016)
Aberration correction for direct laser written waveguides in a transverse geometry.
in Optics express
Humphreys PC
(2014)
Strain-optic active control for quantum integrated photonics.
in Optics express
Jesacher A
(2013)
Refractive index profiling of direct laser written waveguides: tomographic phase imaging
in Optical Materials Express
Jesacher A
(2010)
Parallel direct laser writing in three dimensions with spatially dependent aberration correction.
in Optics express
Jesacher A
(2009)
Adaptive harmonic generation microscopy of mammalian embryos.
in Optics letters
Jesacher A
(2010)
Adaptive optics for direct laser writing with plasma emission aberration sensing.
in Optics express
MacLachlan DG
(2016)
Development of integrated mode reformatting components for diffraction-limited spectroscopy.
in Optics letters
Marshall GD
(2011)
Three-dimensional imaging of direct-written photonic structures.
in Optics letters
Rahman SA
(2013)
Direct wavefront sensing in adaptive optical microscopy using backscattered light.
in Applied optics
Salter P
(2012)
Dynamic control of directional asymmetry observed in ultrafast laser direct writing
in Applied Physics Letters
Salter P
(2013)
Analysis of the Three-Dimensional Focal Positioning Capability of Adaptive Optic Elements
in International Journal of Optomechatronics
Salter PS
(2012)
Focussing over the edge: adaptive subsurface laser fabrication up to the sample face.
in Optics express
Salter PS
(2012)
Adaptive slit beam shaping for direct laser written waveguides.
in Optics letters
Salter PS
(2011)
Addressable microlens array for parallel laser microfabrication.
in Optics letters
Salter PS
(2014)
Exploring the depth range for three-dimensional laser machining with aberration correction.
in Optics express
Simmonds R
(2013)
Modelling of multi-conjugate adaptive optics for spatially variant aberrations in microscopy
in Journal of Optics
Simmonds RD
(2011)
Three dimensional laser microfabrication in diamond using a dual adaptive optics system.
in Optics express
Simmonds RD
(2012)
Effects of aberrations and specimen structure in conventional, confocal and two-photon fluorescence microscopy.
in Journal of microscopy
Smith CW
(2011)
Agitation-free multiphoton microscopy of oblique planes.
in Optics letters
Spring JB
(2013)
On-chip low loss heralded source of pure single photons.
in Optics express
Sun B
(2015)
Pulse front adaptive optics in two-photon microscopy.
in Optics letters
Sun B
(2015)
Pulse front adaptive optics: a new method for control of ultrashort laser pulses.
in Optics express
Thayil A
(2010)
The influence of aberrations in third harmonic generation microscopy
in Journal of Optics
Thayil A
(2011)
Self calibration of sensorless adaptive optical microscopes
in Journal of the European Optical Society: Rapid Publications
Thayil A
(2011)
Long-term imaging of mouse embryos using adaptive harmonic generation microscopy.
in Journal of biomedical optics
Wang B
(2009)
Optimum deformable mirror modes for sensorless adaptive optics
in Optics Communications
Watanabe T
(2010)
Characterisation of the dynamic behaviour of lipid droplets in the early mouse embryo using adaptive harmonic generation microscopy.
in BMC cell biology
Zhou G
(2009)
Axial birefringence induced focus splitting in lithium niobate.
in Optics express
| Description | Numerous new methods were introduced to improve the capabilities of optical microscopes and laser-based micro/nano-fabrication systems. At a fundamental level, new theoretical methods for adaptive optics were developed, providing new approaches to current challenges in this field. Adaptive optics was incorporated in a range of high resolution microscopes, enabling significant improvements in the ability to image at depth inside specimens. These microscopes were used for applications in biomedical research, permitting the observation of biological processes in thick tissue specimens, rather than simply cells on microscope slides. Other methods were developed for laser-based micro and nano-fabrication. The use of adaptive optics enable fabrication of three-dimensional structures inside materials, including photonics crystals, waveguide circuits and diamond structures. Other advances involved the parallelisation of laser writing methods in order to increase fabrication speed. These methods will be used in future manufacturing applications. |
| Exploitation Route | The technologies developed in this project could be used in an industrial context, such as improved optical microscopes and new methods for manufacturing. This research is leading to better microscopes that can be used extensively in a range of scientific areas, most particularly in biomedical research. The development of new laser fabrication techniques is providing a practical route to the use of this technology in wider contexts, including manufacture of more complex optical and photonics devices. |
| Sectors | Digital/Communication/Information Technologies (including Software),Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other |
| Description | The methods for aberration correction in microscopes are being adopted for many applications in biomedical research, where the need to obtain accurate and clear images from deep inside specimens is essential to improve scientific understanding. Dynamic laser machining is now being employed to create light handling chips for quantum optical processing, a method that could transform computation and communications. These machining methods are also being applied to the fabrication of intricate diamond structures, which will have numerous industrial applications. These technologies have now formed the basis of a spin-off company providing laser machining services and instrumentation. |
| First Year Of Impact | 2013 |
| Sector | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Retail |
| Impact Types | Economic |
| Description | EPSRC Programme Grant |
| Amount | £3,504,134 (GBP) |
| Funding ID | EP/K032518/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2013 |
| End | 04/2018 |
| Description | ERC Advanced Grant |
| Amount | € 3,234,789 (EUR) |
| Funding ID | 695140 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 09/2016 |
| End | 08/2021 |
| Description | Flexcos research grant |
| Amount | £347,004 (GBP) |
| Funding ID | EP/M017923/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2015 |
| End | 04/2018 |
| Description | Funding from BBSRC |
| Amount | £116,277 (GBP) |
| Funding ID | BB/J020907/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2013 |
| End | 01/2014 |
| Description | Funding from EPSRC Bright IDEAS scheme |
| Amount | £239,502 (GBP) |
| Funding ID | EP/H049037/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2010 |
| End | 02/2012 |
| Description | Funding from Wellcome Trust |
| Amount | £873,480 (GBP) |
| Funding ID | 095927/B/11/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2011 |
| End | 09/2016 |
| Description | Funding from the Medical Research Council |
| Amount | £1,979,847 (GBP) |
| Funding ID | MR/K01577X/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2013 |
| End | 01/2018 |
| Description | Grant from EU Framework Programme 7 |
| Amount | € 598,263 (EUR) |
| Funding ID | Caminems |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 07/2009 |
| End | 06/2012 |
| Description | Research Programme Grant from the Leverhulme Trust |
| Amount | £237,648 (GBP) |
| Funding ID | RPG-2013-04 |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2013 |
| End | 04/2016 |
| Description | University of Oxford |
| Amount | £7,600 (GBP) |
| Organisation | University of Oxford |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 06/2012 |
| End | 07/2012 |
| Description | Quantum Oxford |
| Organisation | University of Oxford |
| Department | Department of Physics |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Application of adaptive laser writing methods to the manufacture of photonics devices for quantum optics. |
| Collaborator Contribution | Expertise in quantum optics and applications of quantum photonics technology. |
| Impact | Ongoing. |
| Start Year | 2011 |
| Title | Adaptive correction of aberrations |
| Description | Method for laser fabrication at the edge of devices. |
| IP Reference | GB1206542.1 |
| Protection | Patent application published |
| Year Protection Granted | 2012 |
| Licensed | No |
| Impact | NA |
| Title | Adaptive optics for combined pulse and phase front control |
| Description | Adaptive optics for combined pulse and phase front control of an ultrashort pulsed laser. |
| IP Reference | GB1204846.8 |
| Protection | Patent application published |
| Year Protection Granted | 2012 |
| Licensed | No |
| Impact | NA |
| Title | Laser Fabrication System and Method |
| Description | Method for parallelised laser fabrication. |
| IP Reference | GB1103814.8 |
| Protection | Patent granted |
| Year Protection Granted | 2011 |
| Licensed | No |
| Impact | NA |
| Title | Stimulated emission depletion microscopy |
| Description | Method for controlling a STED microscope using adaptive optics. |
| IP Reference | US 61/692,367 |
| Protection | Patent application published |
| Year Protection Granted | |
| Licensed | No |
| Impact | In process. |
| Company Name | Opsydia Ltd |
| Description | Precision laser machining enabled by adaptive optical technologies for applications in security, branding and sensing. |
| Year Established | 2017 |
| Impact | The company has already in the first few months a significant customer to which laser machining services are being provided. The company employs two full-time scientific staff. |
| Website | http://www.opsydia.com |