Optical Atomic Force Microscopy

Atomic force microscopy (AFM), is a state-of-the-art imagining system that uses a sharp probe to scan backwards and forwards over the surface of an object. The probe tip can have atomic dimensions, meaning that AFM can image the surface of an object at near atomic resolution. However, the limitation of these systems is that, just like with a record player, the needle has to be held by a mechanical arm or cantilever. This restricts the access to the sample and prevents the probing of deep channels or indeed any surface that isn't predominantly horizontal.Our idea is to hold the tip of an AFM in an optical beam, without any mechanical constraint. Optical tweezers use the momentum of light beams to trap and move individual spheres, here we will use them to hold and control the AFM tip - without need for any mechanical fixing.We have shown the use of data-projector technology to shape light beams to hold many objects, and that this can give control over a simple probe. We have also shown that high-speed cameras can measure the force acting on the probe with 100 times greater sensitivity than most AFMs. Finally we have shown that the interface of optical tweezers can be made intuitive, e.g. controlled by iPhone or force-feedback joystick!In this project we will develop our use of video game graphics cards for high-speed control and force-feedback to give the user a tactile interface, perhaps utilising the professional equivalent of a Wii motion controller. We will automate a fully-3D scanning system so that complete surface images will be obtained. We will create new probe types, functionalised to give various contrast enhancements. Initially our images will be of standard AFM test samples, but beyond this benchmarking we have budgeted for visits by leading biophysical researchers to test our new approach in their real applications. These range from cell-to-cell interactions to the differentiation of single stem cells.The project is ambitious breaking new ground in optical tweezers, AFM and imaging technologies, but the track records of the collaborating teams lend credence to the success of this project.

Who will benefit from this research? The impact of this research will be in the life sciences where the optical AFM will open up fields of investigation inaccessible with conventional AFM. This will be important for studying cellular surface structure and the effects of external stimuli. The optical AFM represents a major development in AFM which will also impact materials science. The optical AFM will drive the advancement of associated technologies such as control of nanotools in 3D, 3D force measurements, force feedback in 3D, and the suppression of thermal noise motion. Commercialization of optical AFM is an achievable impact. We have experience of this through our spin-out company Infinitesima Ltd. Commercial interest also exists in the component manufacturers such as Boulder Nonlinear Systems, Hamamatsu, laser (Coherent, M2) and microscope supplies (Olympus, Zeiss, and Nikon). Similarly, AFM companies, particularly those involved also in optical tweezers, such as JPK, will also have a keen interest. The probes for the optical AFM are, of course, of a different specification and structure, and the manufacture of these offers another commercialization opportunity - including for another one of our spin-out companies, NanoTrix. Society will benefit through the research that will be undertaken with this revolutionary instrument both as a result of better understanding of cellular processes but also through the training of Research Associates in state-of-the-art instrumentation and development. How will they benefit from this research? The potential impact of stem cell therapies and cancer cell research on the nation's healthcare is immense, and a lead in this area would have a major wealth-generating impact. A scientific break-through that translates into healthcare therapies and devices could grow a new economic activity increasing UK competitiveness. The ability to identify diseased cardiac cells, to repair and restore normal function through stem-cell treatment of infarcted hearts, and provide new directions in cancer therapy would have major impact in the reduction of the burden on the healthcare system of the chronically ill. Similarly, this new 3D imaging method will provide new knowledge of structure and behaviour of retinal cells which will be of benefit to those suffering from retinal degradation. The development of the optical AFM, with a highly intuitive multi-touch interface, for the manipulation of living cells and the measurement of interaction forces in a controlled environment will bring a new tool and skill set to cell researchers. The project is highly interdisciplinary involving physics, physiology, and clinical medicine. Exposure to this environment will have a major positive impact on the outlook and skills of the research assistants involved in the project. It not only gives specific experience and knowledge in fields outside their individual disciplines, it also encourages and enhances their open-mindedness to interdisciplinary research. What will be done to ensure that they benefit from this research? The interdisciplinary nature of this project provides natural routes to many of the potential beneficiaries of the project. We will develop a dedicated website, as we have done for the holographic assembler, and run dedicated workshops in the use of this optical AFM. We will engage with the public on open days and SET activities. In the past nine years we have worked with the University's enterprise team for exploitation through patenting and spin-out companies. The direct links to the NHS will ensure that the healthcare benefits will reach the appropriate communities and will be optimised for the full impact of this research.