Holographic Micro Flow Meter for Biological Sensing

Ever been caught by a speed camera? Most work by taking two images in quick succession the speed of your car being calculated from the separation of its images. We have invented a similar technique for measuring the speed of micron sized objects moving within a fluid. Our technique relies on optical tweezers, tightly focussed beam of light to trap and hold micro-sized test particles in the fluid. Pulsing the tweezers repeated releases the objects into the fluid flow and the speed camera records their velocity, before the particles are re trapped. The result of many measurements is averaged to give the velocity of the fluid flow to an accuracy of one micron per second. One area where we will apply our technique is micro-fluidics, micron-sized networks of fluid channels allowing the transfer and mixing of chemical reagents, probes or bio-objects. Such systems are the basis of 'lab on chip' technology, cheaper, more compact and faster than their full sized lab equivalents. The small scale of lab chips means that fluid behaviour is non-intuitive, water flow being more like concrete, hence the ability to measure the fluid is both elegant and instructive. Beyond gaining an understanding of micro-fluidic flow, our aim is to apply the technique to various bio-applications. Fluid flow around a cell creates mechanical stress, modifying the cell response with a parameter that is not understood; motile cells can swim in a fluid, but again the interplay between the creation and sensing of fluid flow is poorly understood. We believe that our ability to measure the fluid flow with both spatial and temporal resolution combined with our proven expertise in other imaging and sensing technologies will allow us to address these and many other interesting issues.

The aim of the proposal is to develop a new sensitive sensor technology that will, for the first time provide a method to monitor real-time changes of fluid flow in and around biological and bio-analytical microstructures, with extremely high temporal and spatial resolution. Our new technique is based on modulated holographic optical tweezers with which we deliberately release the particle from the optical trap and map its velocity and direction within the fluid. The velocity field is calculated from successive images (c.f. a speed camera) several millisec apart. Then re-establish the trap and the particle is drawn back into the trap by the gradient force of the tweezers. This process is repeated between 40 and 50 times a second. The velocity, as measured from many such cycles, can be averaged to give a precise value. This value is determined whilst the probe particle is in free flow (when the tweezers beam is off) and is therefore totally independent of any dynamic change in the tweezers performance. Our 'tweezers-speed-camera' technique hence combines the accuracy of PIV with the non-perturbing performance of a trapped particle tweezers. The methods will be implemented on a microscope as an imaging platform and will therefore be ideally suited to making measurements in a range of biological and sensory systems including diagnostic lab-on-a-chip devices, biosensors, isolated cells and their organelles. We are particularly interested in using the flow sensors, in combination with microfluidic systems in order to study two specific biological questions, namely: (i) the effects of shear-stress on single cells; and, in a closely related study (ii) the function of cilia and flagella as sensory organelles as well as actuators of fluid flow. Co-funded by EPSRC Life Science Interface Programme.