A hybrid microfluidic platform for cell-based assays via diffusive and convective trans-membrane perfusion

Area of Science:

• Biomedical Engineering
• Microfluidics
• Cell Biology

Background:

• Membrane-supported cell culture is crucial for mimicking in vivo conditions.
• Microfluidic platforms offer precise control over cellular microenvironments.
• Developing integrated systems for cell culture and drug screening is a key challenge.

Purpose of the Study:

• To present a novel 3D hybrid polymer microfluidic chip with a polycarbonate track-etched membrane (PCTEM) for membrane-supported cell culture.
• To demonstrate the platform's utility for screening antitumor chemotoxic agents, specifically mitomycin C (MMC), on the HL60 myeloid leukemia cell line.
• To evaluate two chip designs for diffusive and convective reagent delivery and their impact on cell viability assays.

Main Methods:

• Fabrication of a 3D hybrid microfluidic chip integrating PCTEM.
• Development of two chip designs for distinct reagent delivery modes (diffusive and convective).
• On-chip cell culture of HL60 cells followed by exposure to varying concentrations of mitomycin C (MMC).
• Off-chip cell viability analysis using the trypan blue dye exclusion assay.

Main Results:

• The microfluidic platform successfully supported HL60 cell culture under both shear-free and through-membrane flow conditions.
• On-chip cell viability assay results were consistent with off-chip measurements.
• Approximately 40% cell survival was observed at a 50 μM concentration of mitomycin C.

Conclusions:

• The developed 3D hybrid microfluidic chip with PCTEM is a versatile platform for membrane-supported cell culture and drug screening.
• The platform enables precise control over reagent exposure time and offers flexibility in membrane choice and potential for parallelization.
• This system provides a reliable method for assessing the cytotoxic effects of chemotherapeutic agents on leukemia cells.