2D15 Microfluidic devices for cell based assay : high-throughput drug dose response assay
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Microfluidic devices for cellKeywords:
Drug response
High-Throughput Screening
High throughput screening system is reviewed primely in this article, with emphasis on factors such as acting targets, suitability of assay methods to various targets, major parameters and efficiency evaluation, which play important roles in designing and implementation of high throughput screening system.
High-Throughput Screening
Screening techniques
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臨床的に明らかに薬疹が確診される患者に対して原因薬剤を追求するために原因薬剤含有白色ワセリンを用いてパッチテスト(閉鎖法)を行い, パッチテスト陰性の症例16例, あるいは何らかの理由によりパッチテストが施行できなかった症例4例, 合計20症例の原因薬剤未確定患者を対象とし, 原因薬剤検索のin vitro検査法として薬剤刺激によるリンパ球のIFN-γ産生の測定を行い, その陽性率を薬剤刺激リンパ球幼若化試験(DLST)と比較検討した。20症例の薬疹患者末梢血リンパ球を原因薬剤を添加して培養し, 培養上清中のIFN-γ活性を測定し, 薬剤無添加状態で患者末梢血リンパ球を培養した培養上清中のIFN-γ活性と比較し, 刺激比180%以上を陽性とした。薬剤刺激によるIFN-γ産生は20症例中9例で陽性(陽性率45%)を示し, 一方, DLSTは19症例中4例で陽性(陽性率21%)を示した。症例数が少ないため両者間の陽性率に統計学的な有意差はなかったが, このようにIFN-γ産生試験ではDLSTと同等以上の陽性率が得られ, パッチテスト陰性あるいは未実施, すなわち原因薬剤未確定薬疹患者においても次のステップの原因薬剤確定のin vitro検査法のひとつになりうる可能性が示唆された。
Drug response
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We report an ultrahigh throughput multi-color microfluidic flow cytometer with 32 detection channels and 64 sheath-flow channels. This flow cytometer is realized by integrating a high N.A. microball lens array with a 3D microfluidic device, which allows introducing cell samples into 32 sample channels, and sheath flows into 64 channel for parallel microfluidic focusing using only two inlets. A throughput of 384,000 cell/sec has been accomplished on a single device.
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This chapter reviews industrial applications of high throughput screening (HTS) technologies. One should define high throughput in the context of homogeneous catalysis. Most work in this area should be more correctly termed medium throughput or, in comparison to biological screening, even low throughput screening. Due to the need for the realization of a robust experimental protocol, only about 100, or less, experiments yielding useful data can be carried out per day. The type of high throughput discussed in the chapter has established itself as a useful and general tool for quickly starting projects (lead discovery) as well as for optimization (parameter screening). Highly automated equipment became available and concepts were developed in this field. At the same time, pharmaceutical companies also began to propagate a philosophy of outsourcing. This led to a bubble, with small companies being established and large companies investing in technology and know how in order to meet this perceived demand.
High-Throughput Screening
Realization (probability)
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Combinatorial materials synthesis methods and high throughput screening techniques have been developed to accelerate the process of materials discovery and optimization. In order to apply combinatorial strategies for the innovative materials technology successfully, there are three main stages involved, that is: (i) design of the material chip; (ii) high throughput synthesis of the chip; and (iii) rapid characterization of the chip.i.e. high throughput screening. Further more,high throughput screening is the most important component of combinatorial materials science and technology, it is a major limitation at present. This paper summarizes varieties of high throughput screening methods including microspot X-ray methods, optical measurement techniques, and a novel evanescent microwave microscope used to characterize structural, optical, magnetic, and electrical properties of samples on inorganic material chips.
High-Throughput Screening
Combinatorial synthesis
Characterization
Screening techniques
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High-Throughput Screening
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Acoustic droplet ejection (ADE) as a means of transferring library compounds has had a dramatic impact on the way in which high-throughput screening campaigns are conducted in many laboratories. Two Labcyte Echo ADE liquid handlers form the core of the compound transfer operation in our 1536-well based ultra-high-throughput screening (uHTS) system. Use of these instruments has promoted flexibility in compound formatting in addition to minimizing waste and eliminating compound carryover. We describe the use of ADE for the generation of assay-ready plates for primary screening as well as for follow-up dose-response evaluations. Custom software has enabled us to harness the information generated by the ADE instrumentation. Compound transfer via ADE also contributes to the screening process outside of the uHTS system. A second fully automated ADE-based system has been used to augment the capacity of the uHTS system as well as to permit efficient use of previously picked compound aliquots for secondary assay evaluations. Essential to the utility of ADE in the high-throughput screening process is the high quality of the resulting data. Examples of data generated at various stages of high-throughput screening campaigns are provided. Advantages and disadvantages of the use of ADE in high-throughput screening are discussed.
High-Throughput Screening
Instrumentation
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Pharmacogenomics
Pharmacodynamics
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High throughput drug screening is an important content of novel drug researches. The works of high throughput drug screening were reviewed in this paper; the bottleneck was also introduced. For example, when the solution is～ μl, some problems are met, and the interaction of chemical with drug target is difficult to detect. Aimed at these, a novel opticalcoded technology based on spectroscopically recognizable barcoded beads is presented for its application in high throughput screening (HTS), and our works on it were also showed.
Screening techniques
High-Throughput Screening
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Abstract Drugs and other exogenous substances may be viewed as agents that exert characteristic effects on cells and tissues, but they may also be regarded as agents on which individuals exert important differential effects. To develop explanatory and predictive insights relevant to pharmacogenetics, pharmacologists are more likely to view the effects of a specific drug from the former perspective, while geneticists are more likely to see them from the latter. From a pharmacological viewpoint, individual responsiveness depends on the intrinsic properties of the drug at hand and can be analyzed from observations of its pharmacokinetic and the pharmacodynamic properties. Often the plasma drug concentration or pattern of drug metabolites correlates with an unusual therapeutic effect or an adverse drug reaction, and observations of parameters such as peak and steady-state levels of the drug in plasma, half-lives of drugs in plasma, the ratio of parent drug to metabolite, or the urinary pattern of drug metabolites are successfully employed to study the doseresponse and dynamics of the response.
Pharmacodynamics
Drug response
Active metabolite
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