Significance Microscopic analysis of cellular architectures within a diseased tissue often provides an independent assay relative to measurements of molecular biomarkers from that same tissue. Both methods may point to the same disease state, but the relationship between the two is often not clear. We explore a connection by investigating how growth factor-driven protein signaling depends upon the distance separating pairs of cancer cells. A thermodynamic-derived theory identifies the intercellular separation that corresponds to the steady state of the signaling. That length scale is found to be the dominant cell separation distance in bulk tissue culture. The approach is tested in one cell line and validated in another, and may provide insight into the diffusive nature of certain brain cancer phenotypes.

We report on a radiopharmaceutical imaging platform designed to capture the kinetics of cellular responses to drugs. Methods: A portable in vitro molecular imaging system comprising a microchip and a β-particle imaging camera permitted routine cell-based radioassays of small numbers of either suspended or adherent cells. We investigated the kinetics of responses of model lymphoma and glioblastoma cancer cell lines to 18F-FDG uptake after drug exposure. Those responses were correlated with kinetic changes in the cell cycle or with changes in receptor tyrosine kinase signaling. Results: The platform enabled direct radioassays of multiple cell types and yielded results comparable to those from conventional approaches; however, the platform used smaller sample sizes, permitted a higher level of quantitation, and did not require cell lysis. Conclusion: The kinetic analysis enabled by the platform provided a rapid (∼1 h) drug screening assay.

Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.

Surface chemistry meets tissue engineering: A novel surface-patterning approach for creating arrays of DNA squares is combined with a unique method for DNA-encoding of cells to construct dense arrays of distinct single cells. The cell patterns can be transferred from the substrate surface into thin hydrogel films, and these layers can be stacked to form 3D tissue constructs.

We describe an automated, self-powered chip based on lateral flow immunoassay for rapid, quantitative, and multiplex protein detection from pinpricks of whole blood. The device incorporates on-chip purification of blood plasma by employing inertial forces to focus blood cells away from the assay surface, where plasma proteins are captured and detected on antibody "barcode" arrays. Power is supplied from the capillary action of a piece of adsorbent paper, and sequentially drives, over a 40 minute period, the four steps required to capture serum proteins and then develop a multiplex immunoassay. An 11 protein panel is assayed from whole blood, with high sensitivity and high reproducibility. This inexpensive, self-contained, and easy to operate chip provides a useful platform for point-of-care diagnoses, particularly in resource-limited settings.

An efficient, site-specific and scalable approach has been developed to produce high-quality and individually addressable conducting polymer nanowire electrode junctions (CPNEJs) in a parallel-oriented array. Polypyrrole and PEDOT conducting polymer nanowires (CPNWs) with uniform diameters (ca. 60-150 nm) were introduced into the desired electrode junctions in a precise manner by performing a three-step constant-current electrochemical process at a low current density and a low concentration of monomers. A low scan rate, cyclic voltammetric method was also employed and gave similar results. These CPNEJ arrays function as a miniaturized sensor for the parallel and real-time detection of gas and organic vapour. The electrochemical approaches utilized allow the conducting polymer chains to self-organize in the CPNWs to form novel polycrystalline structures, observed by high resolution TEM. The weak diffraction rings at 4.88 Å and 4.60 Å were observed for PEDOT and polypyrrole CPNWs, respectively.

Developing biochemical and cell biological assay for screening biomolecules, evaluating their characteristics in biological processes, and determining their pharmacological effects represents a key technology in biomedical research. A PDMS-based integrated microfluidic platform was fabricated and tested for facilitating the labeling of ligand on the nanogram scale and sequential cell binding analysis in a manner that saves both time and reagents. Within this microfluidic platform, ligand labeling, cell immobolization, and optical analysis are performed in a miniaturized, continuous and semi-automated manner. This microfluidic device for ligand labeling and cell analysis is composed of two functional modules: (i) a circular reaction loop for fluorophore-labeling of the ligand and (ii) four parallel-oriented incubation chambers for immobilization of cells, binding of ligand to different cell populations, and optical evaluation of interactions between the labeled ligand and its cell targets. Epidermal growth factor (EGF) as the ligand and different cell lines with various levels of EGF receptor expression have been utilized to test the feasiblity of this microfluidic platform. When compared to studies with traditional Petri dish handling of cells and tissues, or even microwell analyses, experiments with the microfluidic platform described here are much less time consuming, conserve reagents, and are programmable, which makes these platforms a very promising new tool for biological studies.

In this paper, we introduce a new approach for the in situ electrochemical fabrication of an individually addressable array of conducting polymer nanowires (CPNWs) positioned within an integrated microfluidic device and also demonstrate that such an integrated device can be used as a chemical sensor immediately after its construction.

In this paper, we demonstrate a template-free, site-specific, and scalable electrochemical method for the fabrication of individually addressable polyaniline nanoframework electrode junctions in a parallel-oriented array. These polyaniline nanoframeworks, which are composed of numerous intercrossing polyaniline nanowires that have uniform diameters ranging from 40 to 80 nm, can be used for the chemical sensing of HCl and NH_3 gases and ethanol vapor and for sensing the pH of aqueous NaCl solutions.