Applications of Adaptive Focused Acoustics to Compound Management

Nixon, Elizabeth; Holland-Crimmin, Sue; Lupotsky, Brian; Chan, James; Curtis, Jon; Dobbs, Karen; Blaxill, Zoe

doi:10.1177/1087057109335677

Cited by 12 publications

(12 citation statements)

References 5 publications

(5 reference statements)

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“…10 For the most part, these applications use acoustic energy at the higher power end of the range provided by AFA instrumentation. At the lower power end of the acoustic energy range, AFA has been used to promote efficient mixing of solutions 11 and to remove bacteria adhered nonspecifically to microporous filters. 12 We therefore undertook a study to explore the potential of applying low power level AFA energy to improve the performance of microtiter plate ELISAs by (1) accelerating antigen/antibody binding with improved mixing of reaction solutions and (2) reducing NSB by AFA-mediated removal of nonspecifically bound entities.…”

Section: Research-article2014mentioning

confidence: 99%

Adaptive Focused Acoustics (AFA) Improves the Performance of Microtiter Plate ELISAs

Green¹,

Rudd

Laugharn

2014

SLAS Discovery

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We investigated the use of Adaptive Focused Acoustics (AFA) technology to improve the performance of microtiter plate enzyme-linked immunosorbent assays (ELISAs). Experiments were performed with commercially available AFA instrumentation and off-the-shelf 96-well microtiter plate sandwich ELISAs. AFA was applied over a range of acoustic energies, temperatures, and durations to the antigen/antibody binding step of an ELISA for measuring HIV-1 p24 in tissue culture samples. AFA-mediated antigen/antibody binding was enhanced up to 2-fold over passive binding at comparable temperatures and was superior or comparable at low temperature (8-10 °C) to passive binding at 37 °C. Lower nonspecific binding (NSB), lower inter-and intra-assay coefficients of variation (CVs), higher Z′ factors, and lower limits of detection (LODs) were measured in AFA-mediated assays compared with conventional passive binding. In a more limited study, AFA enhancement of antigen/antibody binding and lower NSB was measured in an ELISA for measuring IGFBP-3 in human plasma. We conclude from this study that application of AFA to antigen/antibody binding steps in microtiter plate ELISAs can enhance key assay performance parameters, particularly Z′ factors and LODs. These features render AFA-mediated binding assays potentially more useful in applications such as high-throughput screening and in vitro diagnostics than assays processed with conventional passive antigen/antibody binding steps.

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Section: Research-article2014mentioning

confidence: 99%

Adaptive Focused Acoustics (AFA) Improves the Performance of Microtiter Plate ELISAs

Green¹,

Rudd

Laugharn

2014

SLAS Discovery

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“…The Covaris L8 is an adaptive focused acoustics instrument that uses high-powered acoustic waves to dissolve the compounds. Compound dissolution ensures maximum compound activity by ensuring homogenous samples in DMSO [4]. …”

Section: Chemical-library Managementmentioning

confidence: 99%

Research Spotlight: The University of Kansas High-Throughput Screening Laboratory. Part II: Enabling Collaborative Drug-Discovery Partnerships Through Cutting-Edge Screening Technology

2011

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The University of Kansas High-Throughput Screening (KU HTS) core is a state-of-the-art drug-discovery facility with an entrepreneurial open-service policy, which provides centralized resources supporting public- and private-sector research initiatives. The KU HTS core was established in 2002 at the University of Kansas with support from an NIH grant and the state of Kansas. It collaborates with investigators from national and international academic, nonprofit and pharmaceutical organizations in executing HTS-ready assay development and screening of chemical libraries for target validation, probe selection, hit identification and lead optimization. This is part two of a contribution from the KU HTS laboratory.

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“…Earlier reports have generally shown that methods using both traditional sonication and focused acoustics are relatively soft and show little impact on compound degredation. 9,10 The purity of the compounds was further analyzed over the course of multiple solubilization cycles, as would be required in the compound management environment, to evaluate the combined impact of exposure and solubilization cycles on sample stability. These results (shown as raw data in Suppl.…”

Section: Solubilization Studymentioning

confidence: 99%

Characterization of Short-Term Temperature, Exposure, and Solubilization Effects on Library Compound Quality

et al. 2011

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IntroductIon Multiple groups have recognized that maintaining compound quality is dependent on both storage conditions and sample handling methods.1-3 Our workflows within Amgen have been built around low-volume, single-use operational tubes that are periodically prepared as replicates from high-volume, multiuse archive tubes, both stored at temperatures of -8 or -20 °C. This design minimizes the number of times an archive tube must be accessed by instead relying on the single-use tubes for normal operations. This approach effectively serves the majority of the collection, but we have recently noticed that certain compounds enter stages of high demand for a shortened period (<3 months) of time. These high-demand compounds often require frequent replenishment from multiuse archive tubes, which can affect the number of freeze-thaw cycles a compound undergoes. The extended sample handling time can lead to a decrease in overall order fulfillment efficiency and degradation in sample quality from unnecessary exposure outside of the store. Although one potential solution might be to prepare more initial single-use tubes, it is often hard to predict how much material will be required, and the preferred approach has been to replenish on-demand.One alternative approach is short-term storage at room temperature, which would eliminate the need for thawing and reduce sample handling time. Other groups have shown that compound quality can remain stable for 4 to 6 months 4-6 at room temperature, but the labware was significantly different from our archive operations, leading to questions around the form factor used to store compounds. In this study, we wanted to understand the impact of short-term storage at room temperature as compared to the effect of multiple freeze-thaw cycles on overall compound quality in labware relevant to our operations. For our characterization of freeze-thaw events, we were primarily interested in the cumulative effect of both the freeze-thaw and the water uptake that is common with sample handling during formatting Many compound collections are stored under the same temperature conditions, which can limit flexibility by increasing the processing time required for high-demand compounds. In this study, the authors wanted to evaluate the impact of a hybridstorage approach where high-demand compounds are stored for a shortened time period at room temperature to expedite processing operations. The use of a Covaris adaptive-focused acoustics platform was also characterized as a potential enhancement or alternative to storage at elevated temperatures. This study evaluated the impact of temperature, exposure, and solubilization on overall compound quality for short-term storage. A small library of 25 representative compounds was evaluated over an 18-week period to monitor the change in purity and concentration by high-performance liquid chromatography with ultraviolet detection. The authors concluded that temperature had a significant impact on compound concentration, and the effects due to exposure cycles...

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Applications of Adaptive Focused Acoustics to Compound Management

Cited by 12 publications

References 5 publications

Adaptive Focused Acoustics (AFA) Improves the Performance of Microtiter Plate ELISAs

Adaptive Focused Acoustics (AFA) Improves the Performance of Microtiter Plate ELISAs

Research Spotlight: The University of Kansas High-Throughput Screening Laboratory. Part II: Enabling Collaborative Drug-Discovery Partnerships Through Cutting-Edge Screening Technology

Characterization of Short-Term Temperature, Exposure, and Solubilization Effects on Library Compound Quality

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