Functional precision medicine aims to identify effective treatments for patients without targetable mutations. Current research in oncology screens patient-derived models of cancer using endpoint assays. However, these assays fail to capture dynamic responses and tumor heterogeneity. We developed multiparametric quantitative phase imaging (mQPI), a labelfree technique, to screen single cells in real-time. Our work shows mQPI correlates with endpoint assays in measuring drug response in cells from patient derived xenograft organoids (PDxOs), while also capturing time of response and singlecell heterogeneity. Additionally, we demonstrate that mQPI can differentiate organoids that come from the same patient, but which originated from different sites.
The field of microfluidics provides a robust toolkit for biomedical applications such as disease diagnosis and drug discovery, especially when combined with advanced microscopy techniques. An important challenge facing the combination of microfluidic devices with quantitative microscopy techniques, such as quantitative phase imaging (QPI), is the mismatch in refractive index between channel structures and aqueous media. This mismatch can introduce artifacts at material interfaces due to scattering and, in the case of QPI, phase unwrapping. We will show that these issues can be addressed through the use of MY133-V2000, a UV-curable, fluorinated polymer with a low refractive index similar to water (n = 1.33). MY133-V2000 can be fabricated into microfluidic devices using standard soft lithography techniques based on an SU-8 or polydimethylsiloxane (PDMS) mold. The addition of fluorine reduces the overall polarizability of the material, lowering refractive index. However, this introduces a new challenge due to the typically low adhesion of fluorinated polymers. We will discuss device integration and packaging strategies to overcome this limitation. Using QPI, we will demonstrate measurement of the distribution of cell biomass in live, adherent cells, both in the center of the channel and at the interface with microchannel structures, to demonstrate the dramatic reduction in artifacts due to the matching indices of refraction. We will also discuss applications to other microscopy techniques, including fluorescence. MY133-V2000 therefore provides QPI researchers with the opportunity to leverage the advantages of microfluidics for a diverse range of biomedical applications.
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