Low-cost and straight forward rapid prototyping of flexible microfluidic devices using a desktop digital craft cutter is presented. This rapid prototyping method can consistently achieve microchannels as thin as 200 microm in width and can be used to fabricate three-dimensional (3D) microfluidic devices using only double-sided pressure sensitive adhesive (PSA) tape and laser printer transparency film. Various functional microfluidic devices are demonstrated with this rapid prototyping method. The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment.

The development of ultraminiaturized identification tags has applications in fields ranging from advanced biotechnology to security. This paper describes micrometer-sized glass barcodes containing a pattern of different fluorescent materials that are easily identified by using a UV lamp and an optical microscope. A model DNA hybridization assay using these ''microbarcodes'' is described. Rare earth-doped glasses were chosen because of their narrow emission bands, high quantum efficiencies, noninterference with common fluorescent labels, and inertness to most organic and aqueous solvents. These properties and the large number (>1 million) of possible combinations of these microbarcodes make them attractive for use in multiplexed bioassays and general encoding. Encoded bead bioassays are emerging as an attractive alternative to traditional slide-based microarrays because beadbased bioassays offer multiplexing of both probes and samples (the ''analyte''), and they have significantly fewer drawbacks related to mass transport-limited binding of analytes to the immobilized probes. Several approaches have been described for the fabrication of encoded beads: those in which the coding material is randomly distributed in the bead (1, 2) and those in which the coding material is present in a defined pattern on the bead (3). Because different patterns of the same coding materials (e.g., position and thickness of metal stripes on cylindrical particles) result in distinguishable beads (3), a larger number of uniquely encoded beads can be obtained relative to beads with randomly distributed coding materials (e.g., polymer beads infused with mixtures of quantum dots) (2).Current methods for fabricating encoded beads are limited in terms of either the number of possible codes or the compatibility of the beads with bioassays and fluorescence detection. The most widely used method for making encoded beads, infusing polymer microspheres with mixtures of fluorescent dyes in predefined ratios, is not well suited for the fabrication of large (Ͼ10 5 ) numbers of uniquely distinguishable beads. Trau and coworkers have used silica microspheres containing fluorescent dyes for encoding polymer beads by using split-pool methods, and have also described the formation of dye-doped concentric silica layers around core silica particles (4). There are only a limited number of spectrally well-resolved dyes that do not also interfere with commonly used biological labels. Moreover, measurements of intensities and their ratios are inherently difficult, which limits the number of levels at which a dye can be incorporated to give distinguishable beads. Mixtures of quantum dots embedded in polymer microspheres offer significant advantages over conventional fluorescent dyes because they are relatively more photostable and have narrow emission linewidths (2). However, quantum dots are made of toxic materials (e.g., CdS, CdSe, CdTe) (5), and difficulties distinguishing between codes based on different amounts of the same quantum dots are similar to those ...

This paper reported the identification of a novel optical signature for epidermal growth factor (EGF) receptor signaling in human epidermoid carcinoma A431 cells mediated by EGF. The optical signature was based on dynamic mass redistribution (DMR) in living cells triggered by EGFR activation, as monitored in real time with resonant waveguide grating biosensors. Analysis of the modulation of the EGF-induced DMR signals by a variety of known modulators provided links of various targets to distinct steps in the cellular responses. Results showed that the dynamic mass redistribution in quiescent A431 cells mediated by EGF required EGFR tyrosine kinase activity, actin polymerization, and dynamin and mainly proceeded through MEK. The DMR signals obtained serve as integrated signatures for interaction networks in the EGFR signaling.

We describe a perfusion-based microfluidic device for three-dimensional (3D) dynamic primary human hepatocyte cell culture. The microfluidic device was used to promote and maintain 3D tissue-like cellular morphology and cell-specific functionality of primary human hepatocytes by restoring membrane polarity and hepatocyte transport function in vitro without the addition of biological or synthetic matrices or coagulants. A unique feature of our dynamic cell culture device is the creation of a microenvironment, without the addition of biological or synthetic matrices or coagulants, that promotes the 3D organization of hepatocytes into cord-like structures that exhibit functional membrane polarity as evidenced by the expression of gap junctions and the formation of an extended, functionally active, bile canalicular network.

Considerable advances have been made in the development of micro-physiological systems that seek to faithfully replicate the complexity and functionality of animal and human physiology in research laboratories. Sometimes referred to as “organs-on-chips”, these systems provide key insights into physiological or pathological processes associated with health maintenance and disease control, and serve as powerful platforms for new drug development and toxicity screening. In this Focus article, we review the state-of-the-art designs and examples for developing multiple “organs-on-chips”, and discuss the potential of this emerging technology to enhance our understanding of human physiology, and to transform and accelerate the drug discovery and pre-clinical testing process. This Focus article highlights some of the recent technological advances in this field, along with the challenges that must be addressed for these technologies to fully realize their potential.