RESUMO
With circulating tumor cells (CTCs) playing a critical role in cancer metastasis, the quantitation and characterization of CTCs promise to provide precise diagnostic and prognostic information in service of personalized therapies. However, as CTCs are extremely rare, high yield, high purity strategies are required to target and isolate CTCs from patient samples. Recently, we demonstrated the selective capture of CTCs upon antibody-functionalized polyethylene glycol diacrylate (PEGDA) hydrogels photopolymerized within polydimethylsiloxane (PDMS) microfluidic molds. Isolated CTC purity was subsequently enriched by selectively releasing desired cells from photodegradable hydrogel capture surfaces. However, the fabrication of these acrylate-based hydrogels by photopolymerization is subject to oxygen inhibition, which dramatically affects the physical and chemical properties of hydrogel interfaces formed in proximity to PDMS boundaries. To evaluate how antibody conjugation density and cell capture is impacted by fabrication parameters affected by oxygen inhibition, PEGDA hydrogel features were polymerized within PDMS micromolds under different UV exposure conditions and linker (acrylate-PEG-biotin) concentrations. Predictions of acrylate conversion throughout the hydrogel feature were performed using a 1D reaction-diffusion model that describes oxygen-inhibited photopolymerization. The functional consequences of photopolymerization parameters and solution stoichiometry on CTC capture were experimentally quantified and evaluated. Results show that hydrogel surfaces polymerized under shorter exposure times and with higher linker concentrations display superior functionalization and higher CTC capture efficiency. Conversely, highly cross-linked hydrogel surfaces polymerized under longer exposure times are insensitive to functionalization and display poor capture, regardless of linker concentration. By highlighting the importance of oxygen-inhibited photopolymerization, these findings provide guidelines to design micromolded hydrogels with controlled ligand expression. In addition to enhancing the selective cell capture capacity of immunofunctional hydrogels, the ability to quantifiably design hydrogel interfaces described here will improve the sensitivity of hydrogel biosensors, provide a platform to finely screen cell-matrix interactions, and generally enhance the fidelity of micromolded hydrogel features.
RESUMO
Interactions among ions, molecules, and confining solid surfaces are universally challenging and intriguing topics. Lacking a molecular-level understanding of such interactions in complex organic solvents perpetuates the intractable challenge of simultaneously achieving high permeance and selectivity in selectively permeable barriers. Two-dimensional covalent organic frameworks (COFs) have demonstrated ultrahigh permeance, high selectivity, and stability in organic solvents. Using reactive force field molecular dynamics modeling and direct experimental comparisons of an imine-linked carboxylated COF (C-COF), we demonstrate that unprecedented organic solvent nanofiltration separation performance can be accomplished by the well-aligned, highly crystalline pores. Furthermore, we show that the effective, as opposed to designed, pore size and solvated solute radii can change dramatically with the solvent environment, providing insights into complex molecular interactions and enabling future application-specific material design and synthesis.
RESUMO
We report a new synthetic protocol for preparing highly ordered two-dimensional nanoporous covalent organic frameworks (2D-COFs) based on a quinoxaline backbone. The quinoxaline framework represents a new type of COF that enables postsynthetic modification by placing two different chemical functionalities within the nanopores including layer-to-layer cross-linking. We also demonstrate that membranes fabricated using this new 2D-COF perform highly selective separations resulting in dramatic performance enhancement post cross-linking.
