In contrast to sequence‐specific techniques such as polymerase chain reaction, DNA sequencing does not require prior knowledge of the sample for surveying DNA. However, current sequencing technologies demand high inputs for a suitable library preparation, which typically necessitates DNA amplification, even for single‐molecule sequencing methods. Here, electro‐optical zero‐mode waveguides (eZMWs) are presented, which can load DNA into the confinement of zero‐mode waveguides with high efficiency and negligible DNA fragment length bias. Using eZMWs, highly efficient voltage‐induced loading of DNA fragments of various sizes from ultralow inputs (nanogram‐to‐picogram levels) is observed. Rapid DNA fragment identification is demonstrated by burst sequencing of short and long DNA molecules (260 and 20 000 bp) loaded from an equimolar picomolar‐level concentration mixture in just a few minutes. The device allows further studies in which low‐input DNA capture is essential, for example, in epigenetics, where native DNA is required for obtaining modified base information.
Stable, highly productive mammalian cells are critical for manufacturing affordable and effective biological medicines. Establishing a rational design of optimal biotherapeutic expression systems requires understanding how cells support the high demand for efficient biologics production. To that end, we performed transcriptomics and high‐throughput imaging studies to identify putative genes and morphological features that underpin differences in antibody productivity among clones from a Chinese hamster ovary cell line. During log phase growth, we found that the expression of genes involved in biological processes related to cellular morphology varied significantly between clones with high specific productivity (qP > 35 pg/cell/day) and low specific productivity (qP < 20 pg/cell/day). At Day 10 of a fed‐batch production run, near peak viable cell density, differences in gene expression related to metabolism, epigenetic regulation, and proliferation became prominent. Furthermore, we identified a subset of genes whose expression predicted overall productivity, including glutathione synthetase (Gss) and lactate dehydrogenase A (LDHA). Finally, we demonstrated the feasibility of cell painting coupled with high‐throughput imaging to assess the morphological properties of intracellular organelles in relation to growth and productivity in fed‐batch production. Our efforts lay the groundwork for systematic elucidation of clone performance using a multiomics approach that can guide future process design strategies.
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