Study cellular reponses at the microscale by creating heterogenity in cultured cells using a microfluidic probe

We introduce a new approach to study cellular responses in different cell subpopulations while not disrupting the microenvironments. We believe this might become a useful tool to investigate resistance-related cellular responses in cancer cells. Please click Additional Files below to see the full abstract

Dynamic control of high-voltage actuator arrays by light-pattern projection on photoconductive switches

The ability to control high-voltage actuator arrays relies, to date, on expensive microelectronic processes or on individual wiring of each actuator to a single off-chip high-voltage switch. Here we present an alternative approach that uses on-chip photoconductive switches together with a light projection system to individually address high-voltage actuators. Each actuator is connected to one or more switches that are nominally OFF unless turned ON using direct light illumination. We selected hydrogenated amorphous silicon as our photoconductive material, and we provide complete characterization of its light to dark conductance, breakdown field, and spectral response. The resulting switches are very robust, and we provide full details of their fabrication processes. We demonstrate that the switches can be integrated in different architectures to support both AC and DC-driven actuators and provide engineering guidelines for their functional design. To demonstrate the versatility of our approach, we demonstrate the use of the photoconductive switches in two distinctly different applications control of micrometer-sized gate electrodes for patterning flow fields in a microfluidic chamber, and control of centimeter-sized electrostatic actuators for creating mechanical deformations for haptic displays

Computational Immunohistochemistry: Recipes for Standardization of Immunostaining

Cancer diagnosis and personalized cancer treatment are heavily based on the visual assessment of immunohistochemically-stained tissue specimens. The precision of this assessment depends critically on the quality of immunostaining, which is governed by a number of parameters used in the staining process. Tuning of the staining-process parameters is mostly based on pathologists' qualitative assessment, which incurs inter- and intra-observer variability. The lack of standardization in staining across pathology labs leads to poor reproducibility and consequently to uncertainty in diagnosis and treatment selection. In this paper, we propose a methodology to address this issue through a quantitative evaluation of the staining quality by using visual computing and machine learning techniques on immunohistochemically-stained tissue images. This enables a statistical analysis of the sensitivity of the staining quality to the process parameters and thereby provides an optimal operating range for obtaining high-quality immunostains. We evaluate the proposed methodology on HER2-stained breast cancer tissues and demonstrate its use to define guidelines to optimize and standardize immunostaining

Reconfigurable microfluidics: real-time shaping of virtual channels through hydrodynamic forces

To break the current paradigm in microfluidics that directly links device design to functionality, we introduce microfluidic "virtual channels" that can be dynamically shaped in real-time. A virtual channel refers to a flow path within a microfluidic flow cell, guiding an injected reagent along a user-defined trajectory solely by hydrodynamic forces. Virtual channels dynamically reproduce key microfluidic functionality: directed transport of minute volumes of liquid, splitting, merging and mixing of flows. Virtual channels can be formed directly on standard biological substrates, which we demonstrate by sequential immunodetection at arrays of individual reaction sites on a glass slide and by alternating between local and global processing of surface-adherent cell-block sections. This approach is simple, versatile and generic enough to form the basis of a new class of microfluidic techniques

Fluidic Bypass Structures for Improving the Robustness of Liquid Scanning Probes

Objective: We aim to improve operational robustness of liquid scanning probes. Two main failure modes to be addressed are an obstruction of the flow path of the processing liquid and a deviation from the desired gap distance between probe and sample. Methods: We introduce a multi-functional design element, a microfluidic bypass channel, which can be operated in dc and in ac mode, each preventing one of the two main failure modes. Results: In dc mode, the bypass channel is filled with liquid and exhibits resistive behavior, enabling the probe to passively react to an obstruction. In the case of an obstruction of the flow path, the processing liquid is passively diverted through the bypass to prevent its leakage and to limit the buildup of high pressure levels. In ac mode, the bypass is filled with gas and has capacitive characteristics, allowing the gap distance between the probe and the sample to be monitored by observing a phase shift in the motion of two gas-liquid interfaces. For a modulation of the input pressure at 4 Hz, significant changes of the phase shift were observed up to a gap distance of 25 mu m. Conclusion: The presented passive design element counters both failure modes in a simple and highly compatible manner. Significance: Liquid scanning probes enabling targeted interfacing with biological surfaces are compatible with a wide range of workflows and bioanalytical applications. An improved operational robustness would facilitate rapid and widespread adoption of liquid scanning probes in research as well as in diagnostics