Automated robotic liquid handling/laser-based nephelometry system for high throughput measurement of kinetic aqueous solubility

Dehring, Karen A.; Workman, Heather; Miller, Keith; Mandagere, Arun K.; Poole, Salwa K.

doi:10.1016/j.jpba.2004.07.022

Cited by 72 publications

(34 citation statements)

References 7 publications

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“…Significant progress has also been made in the development of robotic systems for dispensing reagents and media into wells of microplates at a high speed with high accuracy [9]. Liquid handling robots are now available from several companies, for example, Tecan and Beckman Coulter [10].…”

Section: Introductionmentioning

confidence: 99%

Batch Transfer of Zebrafish Embryos Into Multiwell Plates

Zhang

Lü

Gelinas

et al. 2011

IEEE Trans. Automat. Sci. Eng.

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Abstract-This paper reports a prototype cooperative robotic system capable of transferring zebrafish embryos in parallel and depositing a single embryo per well in a 96-well microplate. A cell holding device was developed to trap multiple embryos in a regular pattern. The cell holding device and a microplate were positioned and aligned along multiple axes by the system. Embryo release strategies were systematically studied and compared. Experiments demonstrated that out of the 1056 zebrafish embryos used in experiments (i.e., 44 times parallel transfer into 11 96-well plates), 996 wells were successfully filled with one and only one zebrafish embryo, representing a success rate of 94.3%. Further experiments confirmed that the transferred embryos were able to develop into zebrafish with 100% survival rate.Note to Practitioners-Biological experiments and drug screen require the transfer of individual zebrafish embryos into standard multiwell microplates. Manually pipetting one and only one embryo into each well is tedious and time consuming. Different from the only commercial system for automated zebrafish embryo transfer, which is based on conventional, expensive flow cytometry, the proof-of-principle system reported in this paper utilizes a cell immobilization device and a cooperative robotic mechanism for parallel transfer of zebrafish embryos. The system architecture and transfer techniques promise efficient, cost-effective zebrafish embryo transfer for applications requiring molecule tests on a high number of cells.Index Terms-Batch transfer, control and alignment, cooperative robotic mechanism, drug screen, high-throughput screen (HTS), multiwell microplate, zebrafish embryo.

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Section: Introductionmentioning

confidence: 99%

Batch Transfer of Zebrafish Embryos Into Multiwell Plates

Zhang

Lü

Gelinas

et al. 2011

IEEE Trans. Automat. Sci. Eng.

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Initial screens focus on kinetic solubility measurements for compound libraries since they offer the advantage of short equilibration times and use of dimethylsulfoxide (DMSO) solubilized samples [3][4][5][6]. These assays are well suited for initial binning [6] of compounds and categorizing different chemical series. Computational approaches are an option for small subsets of new chemical entities (NCEs), however applied across diverse discovery sets, these methods still fall short of desired accuracy required for decision making in drug discovery programs [7].…”

Section: Introductionmentioning

confidence: 99%

Automated approach to couple solubility with final pH and crystallinity for pharmaceutical discovery compounds

Seadeek

Ando

Bhattachar

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

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“…[2][3][4] For example, high-throughput measurement of kinetic solubility has been reported using an integrated system of robotic liquid handling, plate handling, and nephelometry detection. 5 To improve the detection sensitivity, highthroughput solubility assays using a UV plate reader have also been developed. 6,7 In all these methods, however, the DMSO cosolvent has to be less than 5% (v/v) in the aqueous buffer in order to avoid solubility enhancement by the presence of DMSO.…”

Section: Introductionmentioning

confidence: 99%

An Automated Screening Assay for Determination of Aqueous Equilibrium Solubility Enabling SPR Study During Drug Lead Optimization

Tan¹,

Semin

Wacker

et al. 2005

JALA: Journal of the Association for Laboratory Automation

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A queous solubility is one of the most critical physicochemical properties to be determined in the process of drug lead optimization. Particularly, an equilibrium solubility method is highly valuable to the study of structure property relationship (SPR), while meeting the needs of analytical sensitivity, reproducibility, and throughput. In this report, an automated solubility assay in a 96-well library format was designed and developed by means of robotic liquid handling, centrifugal separation, and HPLC-UV quantification. Requiring 1 mg of solid compound, this assay was used to determine the equilibrium solubility in three user-selected media, that is, 0.01 N HCl, phosphate buffer saline (PBS), and fasted state simulated intestinal fluid (SIF), with a throughput of up to 192 compounds a week. The assay parameters, including the equilibration time and the separation technique, were optimized to ensure that the thermodynamic solubility was measured at the presence of excess solid compound. A fast gradient HPLC method was developed with single-point on-plate calibration for each compound, followed by a customized 96-well chromatographic data analysis. The reporting solubility range was 1-200 mg/mL, appropriate for oral drug candidate selection at the stage of discovery lead optimization. Based on the test results obtained on the commercially available drugs and Amgen research compounds, this assay was considered to be equivalent to the conventional shake-flask methods. Examples were given to demonstrate that the thermodynamic solubility determined by this assay enabled the SPR study to support drug lead optimization. ( JALA 2005;10:364-73)

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Automated robotic liquid handling/laser-based nephelometry system for high throughput measurement of kinetic aqueous solubility

Cited by 72 publications

References 7 publications

Batch Transfer of Zebrafish Embryos Into Multiwell Plates

Batch Transfer of Zebrafish Embryos Into Multiwell Plates

Automated approach to couple solubility with final pH and crystallinity for pharmaceutical discovery compounds

An Automated Screening Assay for Determination of Aqueous Equilibrium Solubility Enabling SPR Study During Drug Lead Optimization

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