Biomolecular crystals are an emerging class of piezoelectric materials that are both biocompatible and biodegradable, which enables their use in biomedical applications and smart devices while ensuring eco-friendly production and disposal. However, accurate quantification of the piezoelectric response of soft sub-micron crystals remains a significant challenge, as conventional piezoelectric measurement techniques are suited to ceramics, thin films, and polymers. Here, we demonstrate the use of a novel piezoresponse force microscopy (PFM) methodology for robust, reliable quantification of the electromechanical response of biomolecular crystals. As a strong test of high accuracy and precision, we show that PFM, integrated with quantum mechanical (QM) density functional theory (DFT) calculations, can distinguish the piezoelectric responses of near-isopiezoelectric amino acid crystals. We show that a statistical approach, combined with experimental best practices, provides effective piezoelectric coefficients of biomolecular single crystals accurately and unambiguously. This work opens the door to high-throughput screening and characterisation of natural and engineered soft piezoelectric crystals for eco-friendly energy harvesters and biodegradable medical implants, reducing dependence on lead-based and rare-earth-containing piezoelectric materials.

生物分子晶体是一类新兴的压电材料，具有生物相容性和可生物降解性，因此可以在生物医学应用和智能设备中使用，同时确保生态友好的生产和处置。但是，由于传统的压电测量技术适用于陶瓷，薄膜和聚合物，因此准确量化软亚微米晶体的压电响应仍然是一项重大挑战。在这里，我们演示了使用新颖的压电响应力显微镜（PFM）方法对生物分子晶体的机电响应进行鲁棒，可靠的量化。作为对高精度和高精度的强有力测试，我们证明了PFM与量子力学（QM）密度泛函理论（DFT）计算相集成，可以区分近等压电氨基酸晶体的压电响应。我们表明，一种统计方法，结合实验最佳实践，可以准确无误地提供生物分子单晶的有效压电系数。这项工作为高通量筛选和表征用于生态友好型能量收集器和可生物降解的医疗植入物的天然和工程软压电晶体打开了大门，从而减少了对铅基和稀土类压电材料的依赖。