On chip two-photon metabolic imaging for drug toxicity testing

Area of Science:

• Biomedical Engineering
• Cell Biology
• Pharmacology

Background:

• Traditional cell-based assays for drug screening and toxicity testing often lack real-time monitoring capabilities and can be invasive.
• Mimicking in vivo conditions, such as blood flow via perfusion culture, is crucial for accurate cellular response assessment.
• Metabolic imaging offers a label-free approach to evaluate cellular health and function non-invasively.

Purpose of the Study:

• To develop and validate a microfluidic system integrated with metabolic imaging for monitoring cellular drug responses.
• To compare the efficacy of this novel system with traditional well-plate assays for drug toxicity testing.
• To establish a fast, non-invasive, and reliable method for drug screening and real-time monitoring of in vitro cell cultures.

Main Methods:

• Development of a microfluidic system for perfusion cell culture.
• Label-free optical imaging of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) fluorescence.
• Non-invasive evaluation of cellular morphology and redox ratio imaging for drug response assessment.
• Comparison of IC50 values obtained from imaging analysis with MTS assay results.

Main Results:

• The microfluidic system accurately monitored cell viability and drug response.
• Redox ratio imaging provided sensitive and comparable IC50 values to the traditional MTS assay.
• The developed method demonstrated high sensitivity and reliability in drug response evaluation.

Conclusions:

• The integrated microfluidic and metabolic imaging system offers a powerful tool for non-invasive, real-time monitoring of cellular drug responses.
• This approach provides a fast, reliable, and sensitive alternative for drug screening and toxicity testing.
• The system holds potential for advancing in vitro cell culture studies and personalized medicine.