Rapid assembly of living micro-tissues with holographic optical tweezers; Cell 'LEGO' for regenerative medicine

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The headline or sound bite for this project is 'laser-guided positioning of live cells and building of living micro-tissues - a new, cell scale manufacturing process for pharmaceutical testing and regenerative medicine'. The project showcases how scientists from seemingly unrelated backgrounds in tissue engineering and optical physics are collaborating to develop new healthcare technologies. The driver for the project is the increasing need to produce living human tissues, in the culture dish, with structures and functions that are as close as possible to those in the body and to use these in vitro tissues to more effectively test, develop and improve new and existing medicines and therapies. This approach can minimize use of animals in research and also reduce potentially costly, both health and economic, failures with new medicines.Our ability to achieve this ambitious goal of manufacturing living micro-tissues with lasers is underpinned by an instrument called an optical tweezers. Optical tweezers, invented in the 1980s exploit a phenomenon, whereby a tightly focused beam of laser light creates a localized force at its point of focus and has the effect of attracting small particles towards it - a so called optical trap or optical trapping. Suspending the particles within fluid gives a damping force producing a single (laser) beam optical trap that is stable in three dimensions (3D) - by moving the beam of laser light, the trapped particle can be also moved and controlled in multiple directions and subsequently positioned at defined points/locations with 'laser precision'. A range of different types and sizes of particles can be trapped and moved including, 2 micron (one 500th of a millimetre) glass beads to live human cells, which are typically 10 microns (one 100th of a millimetre) in size. Importantly, the properties of the laser, in terms of its power and wavelength are such that it causes little or no damage to cells and certainly in the time taken (seconds/minutes) to trap and move them.An evolution of this instrument is the holographic optical tweezers, where the single laser beam is split to create multiple traps, each capable of holding and moving particles. This is done using a spatial light modulator (SLM), a component typically found in an overhead and/or data projector. The SLM acts as a diffractive optical element, or hologram, and can be continuously updated via a computer program. Thus, multiple traps can be created in 3D and each trap independently controlled and positioned to create predetermined configurations and patterns. Using conventional microscope optics and a joy stick or iPad touch screen, the traps can be visualized in real time and controlled with the dexterity of a 'virtual hand'. Here, we will use this technology to exert hitherto unattainable levels of control over the movements and positioning of live cells, with the predefined precision akin to natural processes of tissue development and formation. With dynamic, precision control at the scale of the individual cell, we will show how holographic optical tweezers can be used to manufacture definable and tuneable, 3D micro-tissues; micro-tissue components, such as cells or small (~5 micron) polymer particles containing drugs, can be assembled together within minutes in a manner similar to building with 'cell LEGO'. With inherent control over manufacturing complexity we can deliver 'simple' 3D cell aggregates with applications in drug discovery and pharmaceutical testing, each aggregate consistent with the next, assembled with an exact number of cells and drug-loaded microparticles. This will be the focus of this phase of the project. Developing the project further we will also seek to push the boundaries for manufacture of more complex, bespoke structures that mimic specific tissues like liver, skin, heart etc and can be used to better understand disease processes and develop new therapies.