A self‐regulating cell culture analog device to mimic animal and human toxicological responses

Shuler, M. L.; Ghanem, Ahmed N; Quick, Deborah J.; Wong, Ming-Ching; Miller, Paula

doi:10.1002/(sici)1097-0290(19961005)52:1<45::aid-bit5>3.3.co;2-0

Cited by 15 publications

(22 citation statements)

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“…Lung and liver-related cell lines were cultured in the two bottles separately, and toxicity of naphthalene and its metabolites generated from the liver cell line was observed. Since the first development, several variations of the device were developed, along with a mathematical PBPK model that described the system [65][66][67][68].…”

Section: Microscale Cell Culture Analog (Lcca) Based On a Pbpk Modelmentioning

confidence: 99%

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In vitro microscale systems for systematic drug toxicity study

Sung

Shuler

2009

Bioprocess Biosyst Eng

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After administration, drugs go through a complex, dynamic process of absorption, distribution, metabolism and excretion. The resulting time-dependent concentration, termed pharmacokinetics (PK), is critical to the pharmacological response from patients. An in vitro system that can test the dynamics of drug effects in a more systematic way would save time and costs in drug development. Integration of microfabrication and cell culture techniques has resulted in 'cells-on-a-chip' technology, which is showing promise for high-throughput drug screening in physiologically relevant manner. In this review, we summarize current research efforts which ultimately lead to in vitro systems for testing drug's effect in PK-based manner. In particular, we highlight the contribution of microscale systems towards this goal. We envision that the 'cells-on-a-chip' technology will serve as a valuable link between in vitro and in vivo studies, reducing the demand for animal studies, and making clinical trials more effective.

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Section: Microscale Cell Culture Analog (Lcca) Based On a Pbpk Modelmentioning

confidence: 99%

“…The concept of pharmacokinetic-based testing has been demonstrated at a proof-of-concept level [68,[70][71][72]. In particular, combination of a mathematical modeling approach such as a PBPK modeling and an in vitro platform such as a lCCA can provide a valuable insight into the mechanisms for drug toxicity [66].…”

Section: Outlook and Conclusionmentioning

confidence: 99%

In vitro microscale systems for systematic drug toxicity study

Sung

Shuler

2009

Bioprocess Biosyst Eng

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“…The Cell Culture Analogue Concept. The basic concept for a cell culture analogue device has been described elsewhere (70,71). The motivation for development of a CCA comes from the need for alternative methods to predict human response to exposure to chemicals or pharmaceuticals.…”

Section: Cell Culture Analogs (Ccas)mentioning

confidence: 99%

Integration of Cell Culture and Microfabrication Technology

Park

Shuler

2003

Biotechnology Progress

479

337

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Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

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“…A cell culture analog (CCA) system can be used as a preliminary toxicological and pharmacological test [1]. Development of microfabrication technology has allowed a microscale cell culture analog (µCCA) chip to be more suitable for a toxicological and pharmacological tests [2].…”

Section: Introductionmentioning

confidence: 99%

Real-time quantitative fluorescence measurement of microscale cell culture analog systems

Kim²,

Tatosian

et al. 2007

SPIE Proceedings

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A microscale cell culture analog (µCCA) is a cell-based lab-on-a-chip assay that, as an animal surrogate, is applied to pharmacological studies for toxicology tests. A µCCA typically comprises multiple chambers and microfluidics that connect the chambers, which represent animal organs and blood flow to mimic animal metabolism more realistically. A µCCA is expected to provide a tool for high-throughput drug discovery. Previously, a portable fluorescence detection system was investigated for a single µCCA device in real-time. In this study, we present a fluorescence-based imaging system that provides quantitative real-time data of the metabolic interactions in µCCAs with an emphasis on measuring multiple µCCA samples simultaneously for high-throughput screening. The detection system is based on discrete optics components, with a high-power LED and a charge-coupled device (CCD) camera as a light source and a detector, for monitoring cellular status on the chambers of each µCCA sample. Multiple samples are characterized mechanically on a motorized linear stage, which is fully-automated. Each µCCA sample has four chambers, where cell lines MES-SA/DX-5, and MES-SA (tumor cells of human uterus) have been cultured. All cell-lines have been transfected to express the fusion protein H2B-GFP, which is a human histone protein fused at the amino terminus to EGFP. As a model cytotoxic drug, 10 µM doxorubicin (DOX) was used. Real-time quantitative data of the intensity loss of enhanced green fluorescent protein (EGFP) during cell death of target cells have been collected over several minutes to 40 hours. Design issues and improvements are also discussed.

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A self‐regulating cell culture analog device to mimic animal and human toxicological responses

Cited by 15 publications

References 0 publications

In vitro microscale systems for systematic drug toxicity study

In vitro microscale systems for systematic drug toxicity study

Integration of Cell Culture and Microfabrication Technology

Real-time quantitative fluorescence measurement of microscale cell culture analog systems

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