The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors.
Biotechnol Prog
; 20(1): 338-45, 2004.
Article
em En
| MEDLINE
| ID: mdl-14763861
ABSTRACT
Whole animal testing is an essential part in evaluating the toxicological and pharmacological profiles of chemicals and pharmaceuticals, but these experiments are expensive and cumbersome. A cell culture analog (CCA) system, when used in conjunction with a physiologically based pharmacokinetic (PBPK) model, provides an in vitro supplement to animal studies and the possibility of a human surrogate for predicting human response in clinical trials. A PBPK model mathematically simulates animal metabolism by modeling the absorption, distribution, metabolism, and elimination kinetics of a chemical in interconnected tissue compartments. A CCA uses mammalian cells cultured in interconnected chambers to physically represent the corresponding PBPK. These compartments are connected by recirculating tissue culture medium that acts as a blood surrogate. The purpose of this article is to describe the design and basic operation of the microscale manifestation of such a system. Microscale CCAs offer the potential for inexpensive, relatively high throughput evaluation of chemicals while minimizing demand for reagents and cells. Using microfabrication technology, a three-chamber ("lung"-"liver"-"other") microscale cell culture analog (microCCA) device was fabricated on a 1 in. (2.54 cm) square silicon chip. With a design flow rate of 1.76 microL/min, this microCCA device achieves approximate physiological liquid-to-cell ratio and hydrodynamic shear stress while replicating the liquid residence time parameters in the PBPK model. A dissolved oxygen sensor based on collision quenching of a fluorescent ruthenium complex by oxygen molecules was integrated into the system, demonstrating the potential to integrate real-time sensors into such devices.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Consumo de Oxigênio
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Técnicas Biossensoriais
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Técnicas de Cultura de Células
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Mucosa Respiratória
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Hepatócitos
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Biomimética
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Microfluídica
Tipo de estudo:
Evaluation_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biotechnol Prog
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA