Multiplexed Dosing Assays by Digitally Definable Hydrogel Volumes

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Personalized medicine requires sensitive drug assays using minimal cell or tissue volumes.
• Current methods for multiplexed drug sensitivity testing can be costly and complex.
• Patient-specific combination chemotherapy necessitates precise control over drug dosing.

Purpose of the Study:

• To develop a flexible, cost-efficient method for producing multiplexed drug dosing assays.
• To demonstrate precise quantitative dosing of multiple compounds within hydrogel matrices.
• To validate the assay's utility for personalized medicine applications, including chemotherapy.

Main Methods:

• Spatially defined projected light photopolymerization of hydrogels with embedded active compounds.
• Utilizing high-resolution light projector technology to define individual compound doses.
• Employing poly(ethylene glycol) diacrylates (PEGDA) for hydrogel matrix formation and tuning.
• Demonstrating dosing of hydrophilic/hydrophobic compounds and liposomal drug delivery.

Main Results:

• Quantitative dosing of multiple proteins (fluorescently labeled albumins) with a 1-2 order of magnitude dynamic range.
• Successful dosing of hydrophilic and hydrophobic chemotherapy agents (oxaliplatin, SN-38, 5-fluorouracil, folinic acid).
• Cytotoxicity studies showed equivalent effects for dissolved versus released compounds.
• Demonstrated stable liposomal encapsulation and heat-triggered release of oxaliplatin.

Conclusions:

• Projected light photopolymerization offers a versatile and cost-effective approach for multiplexed drug sensitivity assays.
• The developed hydrogel-based assay enables precise, customizable drug dosing for personalized medicine.
• This technology has significant potential for advancing patient-specific combination chemotherapy and drug delivery research.