SBIR Phase I: Superpenetration Multiphoton Microscopy with MEMS SLMs

This Small Business Innovation Research Program (SBIR) Phase I project aims to develop and demonstrate a superpenetration multiphoton microscope (S-MPM) that will more than double the imaging depth achievable in highly scattering biological tissue. MPM technology has revolutionized the field of subsurface biological imaging, but its depth of penetration is limited. The severe scattering introduced by biological tissue - especially neural tissue - prevents most commercial MPM instruments imaging beyond a few scattering mean free paths. With this limitation, research on cells and cell networks at the frontier of neuroscience is constrained. A recent breakthrough in coherent light propagation and control through highly scattering media demonstrated the possibility of enhancing focal intensity by factors of several hundred on the far side of a medium, despite any amount of scattering, by using a spatial light modulator to modify the phase of the coherent light on the near side of the medium. This project will combine MPM and BMC's fast microelectromechanical spatial light modulators (MEMS SLMs) to offer a compelling and affordable way to exploit this breakthrough in optical science that will make a substantial impact on biomedical and neurobiological research. The broader impact/commercial potential of this project is to substantially improve multiphoton microscopy techniques that have grown exponentially in importance over the past two decades. If successful, the research outcomes will have broad impact on the field of neurobiology by allowing researchers to routinely probe molecular-scale structures and functions at depths of up to 1mm in brain tissue. This enhanced capability will effectively double the achievable penetration depth, with only modest additional instrument cost. The MEMS SLM work that comprises the bulk of the Phase I work plan will generate an important new commercial component, a fast, low cost, MEMS SLM subsystem. Since the proposed instrument will only require use of less than half of the MEMS SLM dynamic range, the drive electronics can be reduced in size and simplified allowing easy integration and significantly reducing cost by using off-the-shelf components and at the same time increase the temporal bandwidth of the system.. The result will be a fivefold reduction in cost and a fivefold increase in speed, which will also have a significant impact on other commercial applications such as free-space laser communication, femtosecond laser.