The regulation of cell growth has fundamental physiological, biotechnological and medical implications. However, methods that can continuously monitor individual cells at sufficient mass and time resolution hardly exist. Particularly, detecting the mass of individual microbial cells, which are much smaller than mammalian cells, remains challenging. Here, we modify a previously described cell balance (‘picobalance’) to monitor the proliferation of single cells of the budding yeast, Saccharomyces cerevisiae, under culture conditions in real time. Combined with optical microscopy to monitor the yeast morphology and cell cycle phase, the picobalance approaches a total mass resolution of 0.45 pg. Our results show that single budding yeast cells (S/G2/M phase) increase total mass in multiple linear segments sequentially, switching their growth rates. The growth rates weakly correlate with the cell mass of the growth segments, and the duration of each growth segment correlates negatively with cell mass. We envision that our technology will be useful for direct, accurate monitoring of the growth of single cells throughout their cycle.

细胞生长的调节具有基本的生理学、生物技术和医学意义。然而，几乎不存在能够以足够的质量和时间分辨率连续监测单个细胞的方法。特别是，检测比哺乳动物细胞小得多的单个微生物细胞的质量仍然具有挑战性。在这里，我们修改了先前描述的细胞平衡（'picobalance'）以监测发芽酵母，酿酒酵母的单细胞增殖，在实时培养条件下。结合光学显微镜监测酵母形态和细胞周期阶段，皮克天平的总质量分辨率接近 0.45 pg。我们的结果表明，单个出芽酵母细胞（S/G2/M 期）依次增加多个线性区段的总质量，从而改变它们的生长速率。生长速率与生长段的细胞质量弱相关，每个生长段的持续时间与细胞质量呈负相关。我们设想，我们的技术将有助于直接、准确地监测单细胞在整个周期中的生长情况。