Art-on-a-Chip: Preserving Microfluidic Chips for Visualization and Permanent Display.

"After a certain high level of technical skill is achieved, science and art tend to coalesce in aesthetics, plasticity, and form. The greatest scientists are always artists as well." said Albert Einstein.

Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring.

The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high-paced workflows necessary to support modern large molecule drug discovery. A high-level aspiration is a true integration of "lab-on-a-chip" methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development.

Ion channel pharmacology under flow: automation via well-plate microfluidics.

Automated patch clamping addresses the need for high-throughput screening of chemical entities that alter ion channel function. As a result, there is considerable utility in the pharmaceutical screening arena for novel platforms that can produce relevant data both rapidly and consistently. Here we present results that were obtained with an innovative microfluidic automated patch clamp system utilizing a well-plate that eliminates the necessity of internal robotic liquid handling.

Well plate microfluidic system for investigation of dynamic platelet behavior under variable shear loads.

The study of platelet behavior in real-time under controlled shear stress offers insights into the underlying mechanisms of many vascular diseases and enables evaluation of platelet-focused therapeutics. The two most common methods used to study platelet behavior at the vessel wall under uniform shear flow are parallel plate flow chambers and cone-plate viscometers. Typically, these methods are difficult to use, lack experimental flexibility, provide low data content, are low in throughput, and require large reagent volumes.

Using well-plate microfluidic devices to conduct shear-based thrombosis assays.

Shear stress plays a critical role in regulating platelet adhesion and thrombus formation at the site of vascular injury. As such, platelets are often examined in vitro under controlled shear flow conditions for their hemostatic and thrombotic functions. Common shear-based platelet analyses include the evaluation of genetic mutants, inhibitory or experimental compounds, matrix substrates, and the effects of different physiological and pathological shear forces.

IonFlux: a microfluidic patch clamp system evaluated with human Ether-à-go-go related gene channel physiology and pharmacology.

Ion channel assays are essential in drug discovery, not only for identifying promising new clinical compounds, but also for minimizing the likelihood of potential side effects. Both applications demand optimized throughput, cost, and predictive accuracy of measured membrane current changes evoked or modulated by drug candidates. Several competing electrophysiological technologies are available to address this demand, but important gaps remain.

Continuous differential impedance spectroscopy of single cells.

A device for continuous differential impedance analysis of single cells held by a hydrodynamic cell trapping is presented. Measurements are accomplished by recording the current from two closely-situated electrode pairs, one empty (reference) and one containing a cell. We demonstrate time-dependent measurement of single cell impedance produced in response to dynamic chemical perturbations.

Platelet adhesion and aggregation under flow using microfluidic flow cells.

Platelet aggregation occurs in response to vascular injury where the extracellular matrix below the endothelium has been exposed. The platelet adhesion cascade takes place in the presence of shear flow, a factor not accounted for in conventional (static) well-plate assays. This article reports on a platelet-aggregation assay utilizing a microfluidic well-plate format to emulate physiological shear flow conditions.

Expansion channels for low-pass filtering of axial concentration gradients in microfluidic systems.

Chemical gradients that run axially in a microfluidic channel often contain undesirable high-frequency concentration variations, or noise, that results from mechanical and thermal fluctuations in the system. In this paper, we describe a passive microfluidic component called an 'expansion channel' (EC), that removes high frequency noise through axial dispersion. We show that the behavior of the filter can be modeled analytically, using an expression for the transfer function of the microfluidic channel, derived by Xie et al.

A low-cost, manufacturable method for fabricating capillary and optical fiber interconnects for microfluidic devices.

Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels.

Integrated microfluidic cell culture and lysis on a chip.

We present an integrated microfluidic cell culture and lysis platform for automated cell analysis that improves on systems which require multiple reagents and manual procedures. Through the combination of previous technologies developed in our lab (namely, on-chip cell culture and electrochemical cell lysis) we have designed, fabricated, and characterized an integrated microfluidic platform capable of culturing HeLa, MCF-7, Jurkat, and CHO-K1 cells for up to five days and subsequently lysing the cells without the need to add lysing reagents. On-demand lysis was accomplished by local hydroxide ion generation within microfluidic chambers, releasing both proteinacious (GFP) and genetic (Hoescht-stained DNA) material.