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Standalone Lab-on-a-Chip Systems toward the Evaluation of Therapeutic Biomaterials in Individualized Disease
Danny Jian Hang Tng1, Peiyi Song1, Rui Hu1
1School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
Abstract:
As each tumor is unique, treatments should be individualized in terms of their drug formulation and time dependent dosing. In vitro lab-on-a-chip (LOC) drug testing is a viable avenue to individualize treatments. A drug testing platform in the form of a customizable standalone LOC system is proposed for treatment individualization in vitro. The platform was used to individualize the treatment of pancreatic cancer by using PANC-1 and MIA PaCa-2 cell lines cultured on-chip. Using on-chip drug uptake, growth, and migration inhibition assays, the therapeutic effect of various treatment combinations was analyzed. Thereafter, optimized treatments were devised for each cell line. The individualized dosage for MIA PaCa-2 cell line was found to be between 0.05-0.1 μg/μL of doxorubicin (DOX), where the greatest growth and migration inhibition effects were observed. As the PANC-1 cell line showed resistance to DOX only formulations, a multidrug approach was used for individualized treatment. Compared to the DOX only formulations, the individualized treatment produced the same degree of migration inhibition but with 5-10 times lower concentration of DOX, potentially minimizing the side-effects of the treatment. Furthermore, the individualized treatment had an average of 672.4% higher rate of growth inhibition. Finally, a preliminary study showed how a tested formulation from the LOC system can be translated for use by employing a nanoparticle system for controlled delivery, producing similar therapeutic effects. The use of such systems in clinical practice could potentially revolutionize treatment formulation by maximizing the therapeutic effects of existing treatments while minimizing their potential side effects through individualization of treatment.
Insights
Individualized cancer treatment using lab-on-a-chip (LOC) drug testing optimizes drug dosage and combinations. This approach enhances therapeutic effects and minimizes side effects for personalized medicine.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery Systems
Background:
- Tumor heterogeneity necessitates individualized treatment strategies.
- Current in vitro drug testing methods lack the precision for personalized dosing.
- Lab-on-a-chip (LOC) technology offers a promising platform for customized drug screening.
Purpose of the Study:
- To develop and validate a customizable LOC system for in vitro individualization of pancreatic cancer treatment.
- To analyze the therapeutic effects of various drug combinations on specific pancreatic cancer cell lines.
- To determine optimized drug formulations and dosages for enhanced efficacy and reduced toxicity.
Main Methods:
- Development of a standalone, customizable LOC platform.
- Culture of PANC-1 and MIA PaCa-2 pancreatic cancer cell lines on-chip.
- Conducting on-chip assays for drug uptake, cell growth inhibition, and migration inhibition.
Main Results:
- Individualized doxorubicin (DOX) dosage for MIA PaCa-2 cells identified (0.05-0.1 μg/μL) for maximal growth and migration inhibition.
- PANC-1 cells, resistant to DOX alone, showed effective treatment via a multidrug approach.
- Individualized treatment achieved comparable migration inhibition with 5-10x lower DOX concentration and significantly higher growth inhibition (672.4%) compared to DOX-only formulations.
Conclusions:
- The developed LOC platform enables effective in vitro individualization of pancreatic cancer treatment.
- Optimized multidrug strategies can overcome drug resistance and improve therapeutic outcomes.
- LOC-based personalized treatment has the potential to revolutionize drug formulation, maximizing efficacy while minimizing side effects.

