This paper introduces a new method of data-driven microscope design for virtual fluorescence microscopy. We use a deep neural network (DNN) to effectively design optical patterns for specimen illumination that substantially improve upon the ability to infer fluorescence image information from unstained microscope images. To achieve this design, we include an illumination model within the DNN’s first layers that is jointly optimized during network training. We validated our method on two different experimental setups, with different magnifications and sample types, to show a consistent improvement in performance as compared to conventional microscope imaging methods. Additionally, to understand the importance of learned illumination on the inference task, we varied the number of illumination patterns being optimized (and thus the number of unique images captured) and analyzed how the structure of the patterns changed as their number increased. This work demonstrates the power of programmable optical elements at enabling better machine learning algorithm performance and at providing physical insight into next generation of machine-controlled imaging systems.

Recent machine learning techniques have dramatically changed how we process digital images. However, the way in which we capture images is still largely driven by human intuition and experience. This restriction is in part due to the many available degrees of freedom that alter the image acquisition process (lens focus, exposure, filtering, etc). Here we focus on one such degree of freedom - illumination within a microscope - which can drastically alter information captured by the image sensor. We present a reinforcement learning system that adaptively explores optimal patterns to illuminate specimens for immediate classification. The agent uses a recurrent latent space to encode a large set of variably-illuminated samples and illumination patterns. We train our agent using a reward that balances classification confidence with image acquisition cost. By synthesizing knowledge over multiple snapshots, the agent can classify on the basis of all previous images with higher accuracy than from naively illuminated images, thus demonstrating a smarter way to physically capture task-specific information.