ArticleAnalytical chemistry2023
Multidimensional Protein Solubility Optimization with an Ultrahigh-Throughput Microfluidic Platform.
Article in Analytical chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization.Nature chemistry · 2026Article
- PhaseXplorer Creates High-Dimensional Phase Diagrams with Closed-Loop Active Learning.ACS nano · 2025Article
- Automated navigation of condensate phase behavior with active machine learning.Nature communications · 2025Article
- Improved MALDI-MS Imaging of Polar andAnalytical chemistry · 2025Article
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-based biologics are highly suitable for drug development as they exhibit low toxicity and high specificity for their targets. However, for therapeutic applications, biologics must often be formulated to elevated concentrations, making insufficient solubility a critical bottleneck in the drug development pipeline. Here, we report an ultrahigh-throughput microfluidic platform for protein solubility screening. In comparison with previous methods, this microfluidic platform can make, incubate, and measure samples in a few minutes, uses just 20 μg of protein (>10-fold improvement), and yields 10,000 data points (1000-fold improvement). This allows quantitative comparison of formulation excipients, such as sodium chloride, polysorbate, histidine, arginine, and sucrose. Additionally, we can measure how solubility is affected by the combinatorial effect of multiple additives, find a suitable pH for the formulation, and measure the impact of mutations on solubility, thus enabling the screening of large libraries. By reducing material and time costs, this approach makes detailed multidimensional solubility optimization experiments possible, streamlining drug development and increasing our understanding of biotherapeutic solubility and the effects of excipients.
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Registered trials
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