Proteins-molecular machines that underpin all biological life-are of significant therapeutic and industrial value. Directed evolution is a high-throughput experimental approach for improving protein function, but has difficulty escaping local maxima in the fitness landscape. Here, we investigate how supervised learning in a closed loop with DNA synthesis and high-throughput screening can be used to improve protein design. Using the green fluorescent protein (GFP) as an illustrative example, we demonstrate the opportunities and challenges of generating training datasets conducive to selecting strongly generalizing models. With prospectively designed wet lab experiments, we then validate that these models can generalize to unseen regions of the fitness landscape, even when constrained to explore combinations of non-trivial mutations. Taken together, this suggests a hybrid optimization strategy for protein design in which a predictive model is used to explore difficultto-access but promising regions of the fitness landscape that directed evolution can then exploit at scale.

A micro-scale, high-force, large displacement and low-voltage piezoelectric actuator has been developed using a compact strain amplifying flextensional mechanism. The device is fabricated using an SU-8 beam structure as an external amplifying mechanism for a thin-film PZT strip (area 11.4 × 10−4 cm2, thickness 0.4 µm) sandwiched between Pt top and bottom electrodes. Each actuator ‘cell’ can be arrayed in series and/or in parallel to accommodate different force/displacement requirements. Testing of the initial prototype design showed a maximum blocking force of 55 µN and a peak displacement of 1.18 µm at 10 V. Fabricated devices consisting of three actuator cells in series were tested, demonstrating a strain amplification ratio in excess of 10:1 per cell.

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