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Solving computationally hard problems using conventional computing architectures is often slow and energetically inefficient. Quantum computing may help with these challenges, but it is still in the early stages of development. A quantum-inspired alternative is to build domain-specific architectures with classical hardware. Here we report a sparse Ising machine that achieves massive parallelism where the flips per second—the key figure of merit—scales linearly with the number of probabilistic bits. Our sparse Ising machine architecture, prototyped on a field-programmable gate array, is up to six orders of magnitude faster than standard Gibbs sampling on a central processing unit, and offers 5–18 times improvements in sampling speed compared with approaches based on tensor processing units and graphics processing units. Our sparse Ising machine can reliably factor semi-primes up to 32 bits and it outperforms competition-winning Boolean satisfiability solvers in approximate optimization. Moreover, our architecture can find the correct ground state, even when inexact sampling is made with faster clocks. Our problem encoding and sparsification techniques could be applied to other classical and quantum Ising machines, and our architecture could potentially be scaled to 1,000,000 or more p-bits using analogue silicon or nanodevice technologies. 

Abstract Genetically encoded reporters have greatly increased our understanding of biology. While fluorescent reporters have been widely used, photostability and phototoxicity have hindered their use in long‐term experiments. Bioluminescence overcomes some of these challenges but requires the addition of an exogenous luciferin limiting its use. Using a modular approach, Autonomous Molecular BioluminEscent Reporter (AMBER), an indicator of membrane potential is engineered. Unlike other bioluminescent systems, AMBER is a voltage‐gated luciferase coupling the functionalities of the Ciona voltage‐sensing domain (VSD) and bacterial luciferase, luxAB. When co‐expressed with the luciferin‐producing genes, AMBER reversibly switches the bioluminescent intensity as a function of membrane potential. Using biophysical and biochemical methods, it is shown that AMBER switches its enzymatic activity from an OFF to an ON state as a function of the membrane potential. Upon depolarization, AMBER switches from a low to a high enzymatic activity state, showing a several‐fold increase in the bioluminescence output (ΔL/L). AMBER in the pharyngeal muscles and mechanosensory touch neurons ofCaenorhabditis elegansis expressed. Using the compressed sensing approach, the electropharingeogram of theC. eleganspharynx is reconstructed, validating the sensor in vivo. Thus, AMBER represents the first fully genetically encoded bioluminescent reporter without requiring exogenous luciferin addition.