Quantum measurement of biology

Abstract

This thesis reports the development of a quantum enhanced microparticle tracking technique, which applied to measurements within living cells, allowed the first demonstrations of both biological measurements beyond the quantum noise limit and quantum enhanced spatial resolution within biology. The sensitivity of any optical measurement is limited by noise which follows from quantization of the electromagnetic field. This thesis theoretically characterizes the resulting quantum limit on particle tracking precision; both in the limit of perfect measurements and for the measurements used in real experiments, and theoretically establishes an experimental strategy which could allow the quantum limit to be surpassed via the application of non-classical light. Further, a computational tool is developed which allows rapid characterization of particle tracking experiments, thus providing researchers the benefit of rigorous theoretical predictions without requiring detailed calculations. Following this, classical technologies are developed which can improve microparticle tracking sensitivity and which are enabling steps toward integration of non-classical light. An interferometric strategy is described whereby signal-to-noise is improved by removing unwanted light from the detector. An optical lock-in technique is developed which eliminates low-frequency noise, thus allowing quantum noise limited performance at low frequencies. This is a crucial requirement for quantum enhanced measurements, and can also improve precision in classical experiments. Dark-field illumination is also explored as a method to remove unwanted background light, and the optimal illumination angle is calculated for our intended experiments. These advances are then applied in the development of the first quantum enhanced particle tracking apparatus. Squeezed states of light are used to improve particle tracking precision by 2.7 dB, demonstrating quantum enhanced microscopy for the first time. This was applied to perform the first measurements of living systems with quantum enhanced precision. Naturally occurring lipid particles were tracked within the cytoplasm of Saccharomyces cerevisiae yeast cells, with squeezed light enhancing precision by 2.4 dB. The thermal motion of these particles could then be analyzed to infer the viscosity and elasticity of the local environment, with squeezed light allowing 64% faster observations, thus improving the sensitivity to dynamic biological changes. This experiment was then extended to spatially resolved quantum imaging, with lipid particles used as scanning probes in a technique called photonic force microscopy. The particles sample variations in the local environment with resolution limited by measurement precision rather than the diffraction limit. The use of squeezed light was found to enhance spatial resolution by 14% at an absolute resolution level of 10 nm, comparable to leading classical experiments. This was the first demonstration of both sub-diffraction limited resolution and quantum enhanced resolution in biology, and places practical applications of quantum imaging within reach. Finally, the future challenges and prospects of quantum enhanced particle tracking are outlined.n