Abstract:In synthetic biology, the dazzling methodological innovations in sequencing, editing and synthesis of genomes have resulted in an unprecedented capability in "design and manufacturing of genotype". On the other hand, "testing of cellular phenotype and function" has increasingly become one major bottleneck. Single-cell technologies have tremendous implications and potentials in rapid testing of cellular function. However, ideally, such single-cell methods should allow non-invasive live-cell probing, be label-free, provide landscapelike phenotyping capability, distinguish complex functions, operate with high speed, sufficient throughput and low-cost, and finally, be able to couple with downstream omics analysis via cell sorting. In this perspective article, we focus on recent progress in label-free molecular spectroscopy-activated phenotyping, sorting and sequencing of single-cells, and discuss the key challenges and emerging trends of the area. We propose that alliance among the array of non-invasive spectroscopy methods or modes, when coupled with downstream high-throughput cell sorting and omics profiling, will establish and broaden a bridge that connects spectroscopy and genetics, in science, technologies, and communities. This bridge will lead to novel and creative solutions to high-throughput, landscape-like testing and screening of synthetic cells. Moreover, it will fulfill the promise of spectroscopy-enabled single-cell "phenome-genome" as a new type of biological big-data, and accelerate the pace of "data-driven" synthetic biology.