Abstract
The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high‐paced workflows necessary to support modern large molecule drug discovery. A high‐level aspiration is a true integration of “lab‐on‐a‐chip” methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light‐induced electrokinetics with micro‐ and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single‐cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low‐throughput bioprocess workflows in biopharma and life science research.
Highlights
INTRODUCTION OF LIGHTINDUCED ELECTROKINETICS AND IMPACT ON BIOLOGICS DISCOVERYA new generation of techniques based on forces exerted by a light beam is enabling interactive biology at the cellular level, opening new opportunities in drug discovery
The on‐chip relative titer ranking (RTR) assay results for IgG secretion from these rapid transient expressions correlate with mAb titer from standard expression cultures as measured by the FortéBio Octet® system, similar to the RTR rankings from stable Chinese hamster ovary (CHO) process (Figure 5b)
Six different fluorescein‐labeled yeast displaying peptides were loaded and penned sequentially in specified chip regions, FIGURE 6 Single‐cell quantitative assay | (a) Workflow schematic: After loading, cells are identified and trapped into light cages facilitating single‐ cell penning via opto‐electro‐ positioning (OEP)
Summary
INTRODUCTION OF LIGHTINDUCED ELECTROKINETICS AND IMPACT ON BIOLOGICS DISCOVERYA new generation of techniques based on forces exerted by a light beam (known as optical manipulations) is enabling interactive biology at the cellular level, opening new opportunities in drug discovery. KEYWORDS advanced biotechnology, bioassay development, digital cell biology, drug discovery, nanoscale cell culture, optical manipulation techniques, single cell technology The integrated technology has the flexibility and capability to enable a broad array of applications applicable to commercial large molecule drug development, including antibody discovery, clonal selection, gene editing, linking phenotype to genotype, and cell line development.
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