When nanoparticles (NPs) are exposed to the biological environment, their surfaces become covered with proteins and biomolecules (e.g. lipids). Here, we report that this protein coating, or corona, reduces the targeting capability of surface engineered NPs by screening the active sites of the targeting ligands.

Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this has been a major barrier for applications to biological systems. Recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.

A microfluidic platform for the construction of microscale components and autonomous systems is presented. The platform combines liquid-phase photopolymerization, lithography, and laminar flow to allow the creation of complex and autonomous microfluidic systems. The fabrication of channels, actuators, valves, sensors, and systems is demonstrated. Construction times can be as short as 10 min, providing ultrarapid prototyping of microfluidic systems. C onstruction of microscale systems generally has been approached from two perspectives. Either the components are fabricated separately and then assembled (as at the macroscale) or lithography-based microfabrication methods are used to create the components at their desired locations (e.g., polysilicon surface micromachining). Assembly of micrometer-sized objects has proven to be nontrivial because electrostatic and other surface forces are overwhelming at the microscale, making manipulation difficult (1). Through appropriate geometric design, these forces can be harnessed to self-assemble small parts (2). Conventional lithographic approaches show promise, but the many disparate materials and processes hinder the fabrication of complex systems. For example, the processes used to construct one system component (e.g., a sensor) may be incompatible with those for other components (e.g., pumps and valves). To realize microscale systems for many different applications, unconventional approaches are needed to overcome these difficulties. The physics of scaling (i.e., laminar flow, high surface-to-volume ratio) can lead to significantly improved performance in some medical and biological applications and also allow for in-channel construction. Whitesides and coworkers (3) have demonstrated several in-channel fabrication techniques that use laminar flow to create textured walls and to build metal traces within microchannels. Smela et al. (4) demonstrated conductive microscale actuators built on flat substrates by patterning conductive polymers using lithography. Two-photon polymerization has been used to create three-dimensional (3D) structures from a polymer gel precursor (5, 6).Previously, we reported the ability to build in-channel autonomous hydrogel valves by using a photopolymerization process (7). It has been demonstrated that stimuli-responsive hydrogels are the natural materials for microfluidic systems in terms of scaling physics because smaller size leads to faster volume changes for these diffusion-controlled processes. Here, we expand this photopolymerization method to a fabrication platform for total system construction. This fabrication platform, which we refer to as microfluidic tectonics (FT), utilizes microfluidics, photopolymerization, and materials chemistry to create autonomous microfluidic systems controlled by the local fluidic environment. FT allows one to develop a wide variety of microfluidic systems by using one common construction platform, providing several key advantages. First, it provides a general, integrated platform for the construction of...

Lateral variations in membrane composition are postulated to play a central role in many cellular events, but it has been difficult to probe membrane composition and organization on length scales of tens to hundreds of nanometers. We present a high-resolution imaging secondary ion mass spectrometry technique to reveal the lipid distribution within a phase-separated membrane with a lateral resolution of approximately 100 nanometers. Quantitative information about the chemical composition within small lipid domains was obtained with the use of isotopic labels to identify each molecular species. Composition variations were detected within some domains.