Atomic layer deposition enables multi-modal three-dimensional electron microscopy of isoporous membranes.

Block copolymers (BCPs) are promising materials for water purification. They enable the fabrication of integral asymmetric isoporous membranes with high permeability and good selectivity. Commonly, the characterization of such hierarchical structures is performed by conventional electron microscopy (EM) means, namely scanning and transmission electron microscopy (SEM and TEM, respectively). However, due to the inherent lack of contrast between BCP domains, external contrast agents are required to achieve informative, high-resolution imaging. In addition, such EM techniques are typically limited to a certain cross-section or surface morphology only. In this paper, we harness the selective growth of AlOx in the pore-forming domains of BCPs to create an internal and stable contrast difference between the blocks. This in turn allowed us to perform advanced three-dimensional characterization of the membranes with focused ion beam (FIB)-SEM and TEM tomography, providing an understanding of the 3D structure and properties such as 3D geometry of the pores, 3D tortuosity, and 3D permeability. This 3D characterization also provides better correlations between the membrane structure and its performance. Such knowledge can allow better design and fine-tuning of BCP membranes and other membranes for their applications.

Hybrid Organic-Inorganic-Organic Isoporous Membranes with Tunable Pore Sizes and Functionalities for Molecular Separation.

Accomplishing on-demand molecular separation with a high selectivity and good permeability is very desirable for pollutant removal and chemical and pharmaceutical processing. The major challenge for sub-10 nm filtration of particles and molecules is the fabrication of high-performance membranes with tunable pore size and designed functionality. Here, a versatile top-down approach is demonstrated to produce such a membrane using isoporous block copolymer membranes with well-defined pore sizes combined with growth of metal oxide using sequential infiltration synthesis and atomic layer deposition (SIS and ALD). The pore size of the membranes is tuned by controlled metal oxide growth within and onto the polymer channels, enabling up to twofold pore diameter reduction. Following the growth, the distinct functionalities are readily incorporated along the membrane nanochannels with either hydrophobic, cationic, or anionic groups via straightforward and scalable gas/liquid-solid interface reactions. The hydrophilicity/hydrophobicity of the membrane nanochannel is significantly changed by the introduction of hydrophilic metal oxide and hydrophobic fluorinated groups. The functionalized membranes exhibit a superior selectivity and permeability in separating 1-2 nm organic molecules and fractionating similar-sized proteins based on size, charge, and hydrophobicity. This demonstrates the great potential of organic-inorganic-organic isoporous membranes for high-performance molecular separation in numerous applications.

Atomic Layer Deposition for Gradient Surface Modification and Controlled Hydrophilization of Ultrafiltration Polymer Membranes.

In recent years, atomic layer deposition (ALD) has emerged as a powerful technique for polymeric membrane surface modification. In this research, we study Al2O3 growth via ALD on two polymeric phase-inverted membranes: polyacrylonitrile (PAN) and polyetherimide (PEI). We demonstrate that Al2O3 can easily be grown on both membranes with as little as 10 ALD cycles. We investigate the formation of Al2O3 layer gradient through the depth of the membranes using high-resolution transmission electron microscopy and elemental analysis, showing that at short exposure times, Al2O3 accumulates at the top of the membrane, reducing pore size and creating a strong growth gradient, while at long exposure time, more homogeneous growth occurs. This detailed characterization creates the knowledge necessary for controlling the deposition gradient and achieving an efficient growth with minimum pore clogging. By tuning the Al2O3 exposure time and cycles, we demonstrate control over the Al2O3 depth gradient and membranes' pore size, hydrophilicity, and permeability. The oil antifouling performance of membranes is investigated using in situ confocal imaging during flow. This characterization technique reveals that Al2O3 surface modification reduces oil droplet surface coverage.

Tin oxide nanostructure fabrication via sequential infiltration synthesis in block copolymer thin films.

Tin oxide (SnO2) nanostructures are attractive for sensing, catalysis, and optoelectronic applications. Here we investigate the fabrication of SnOx nanostructures through sequential infiltration synthesis (SIS) in block copolymer (BCP) film templates. While the growth of metal and metal oxides within polymers and BCP films via SIS has been demonstrated until now using small precursors such as trimethyl aluminum and diethyl zinc, we hypothesize that SIS can be performed using larger precursors and demonstrate SnOx SIS with tetrakis(dimethylamino)tin (TDMASn) and hydrogen peroxide. Tuning the SIS reaction and BCP chemistry resulted in highly ordered, polystyrene-block-poly(2-vinyl pyridine) (P2VP)-templated porous SnOx - AlOx and SnOx nanostructures. Detailed investigation using in-situ microbalance, high resolution electron microscopy, elemental analysis and infra-red spectroscopy shows that SnOx can directly grow within P2VP homopolymer and BCP films. Simultaneously with the growth, SnOx SIS process also contributes to the polymer etch. Performing SnOx SIS with pretreatment of a single AlOx SIS cycle increases the SnOx growth and protects the BCP template from etching. This is the first report of SnOx SIS opening a pathway for additional tetrakis-based organometallic precursors to be utilized in growth processes within polymers.

Collagenase Nanoparticles Enhance the Penetration of Drugs into Pancreatic Tumors.

Overexpressed extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) limits drug penetration into the tumor and is associated with poor prognosis. Here, we demonstrate that a pretreatment based on a proteolytic-enzyme nanoparticle system disassembles the dense PDAC collagen stroma and increases drug penetration into the pancreatic tumor. More specifically, the collagozome, a 100 nm liposome encapsulating collagenase, was rationally designed to protect the collagenase from premature deactivation and prolonged its release rate at the target site. Collagen is the main component of the PDAC stroma, reaching 12.8 ± 2.3% vol in diseased mice pancreases, compared to 1.4 ± 0.4% in healthy mice. Upon intravenous injection of the collagozome, ∼1% of the injected dose reached the pancreas over 8 h, reducing the level of fibrotic tissue to 5.6 ± 0.8%. The collagozome pretreatment allowed increased drug penetration into the pancreas and improved PDAC treatment. PDAC tumors, pretreated with the collagozome followed by paclitaxel micelles, were 87% smaller than tumors pretreated with empty liposomes followed by paclitaxel micelles. Interestingly, degrading the ECM did not increase the number of circulating tumor cells or metastasis. This strategy holds promise for degrading the extracellular stroma in other diseases as well, such as liver fibrosis, enhancing tissue permeability before drug administration.

Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue.

Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We propose that surgical procedures can rely on natural tissue remodeling tools-enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.