Micro-device for analyzing biological fluids

A smart microfluidic control system that is capable of monitoring clinically-relevant parameters can sample, dispense, and deliver biological fluids to a sensing unit.
10 May 2007
Marius Andrei Avram and Marioara Avram

We have designed and implemented a smart microfluidic control system. It consists of microchannels with strategically-located reservoirs and microvalves, logical microfluidic gates and micropumps, and capillary and rotary microviscosity meters. It features an integrated multiplexer and microdispenser based on a nozzle array, and an integrated biosensor array for simultaneous detection of multiple clinically-relevant parameters. Biochip output is inserted into the analyzer unit at the point at which a trigger signal from the electronic controller initiates microfluidic sequencing.

Micro-total analysis and automatic control systems

Much research in the past decade has focused on the development of micro-total-analysis systems (μTAS) and lab-on-a-chip devices.1 μTAS systems have been developed for a number of biochemical operations, frequently for clinical measurements such as blood gas and glucose/lactate levels as well as for DNA sequence analysis. Other applications include proteomics, combinatorial synthesis or analysis, immunoassays, toxicity monitoring, and even forensic analysis.2 The range of uses for μTAS devices is expanding rapidly as more researchers become aware of their significant benefits.1

Researchers have also explored active control devices, including microvalves and micropumps to govern fluid flow. But inherent disadvantages include high cost, difficult integration, fabrication and assembly, and complex control circuitry. A large number and variety of passive microfluidic devices have been successfully demonstrated, including passive valves, mixers, diffusion-based extractors, filters and membranes, and a few actuation schemes.

Figure 1. Microchannel simulations: (a) a straight channel; (b) a bifurcate furcated channel; (c) a constricted channel; (d) a channel patterned like the inside of a blood vessel.

Our approach

To develop efficient smart microfluidic systems it is essential to understand the microscale phenomena that govern properties of fluid flow through microchannels. Microscale differs from macroscale flow in one key aspect: the significance of surface tension forces. In a microfluidic channel (or microchannel), viscous flow reductions are usually matched by surface tension drops across an advancing or receding meniscus.

Choice of substrate material is critical to a smart microfluidic system. Traditionally, most biochemical-analysis systems have used silicon (Si) or glass as substrates for the microfluidic motherboards. However, considerable efforts have been expended to explore other—primarily polymer-based—substrates. These offer numerous advantages, such as low cost, rugged construction, ease of fabrication, and rapid prototyping. A key advantage in using polymers is the wide variety of surface properties they offer, which can be readily modified to meet the fluidic and/or biocompatibility requirements of the biochemical analysis system. Various criteria dictate the choice of substrate material, including ease of processing, physical characteristics (e.g., high mechanical strength), biocompatibility, and cost. The main polymers suffer from certain disadvantages such as low resistance to organic solvents, high gas permeability, and low operating-temperature range. Furthermore, polymer micromachining techniques are still under development and are not as mature as Si/glass processing techniques.

Polymer processing, by contrast, is a mature, established science for macroscale applications, and μTAS researchers can readily exploit the significant data collected by polymer experts to create multi-functional, low-cost, disposable microfluidic modules. Since a hydrophobic surface is essential for smart microfluidic systems, polymer substrates are ideal.

What we've done

To engineer a device capable of performing complex analysis, we must incorporate as many components as possible on a single chip. To this end, we designed, fabricated, and simulated different types of microchannels. We have also developed a magneto-sensitive detection system for the viscosimeter.

Figure 2. Straight and endothelial-profiled microchannels.

Our simulations provide insight into blood flow through vessels. Straight microchannels—as displayed in Figure 1(a)—have shown us how viscosity varies as a function of the diameter of the microchannel. Bifurcated microchannels—as shown in Figure  1(b)—provide information about blood flow through a branching point from larger to smaller blood vessels. Interior roughness is studied by applying a surface contour to the walls of the channels. This surface pattern is comparable to that of the endothelial lining of the vessels. Endothelial cell patterned channel—as shown in Figure  1(d)—provides a means to subject viscoelastic fluids to compression and relaxation. Also, cell motility can be studied with these types of microchannels.

The first test microchannels (see Figure 2) were fabricated on a Corning 7740 glass substrate using wet etching with hydrofluoric-based solutions.3 To design the viscometer, we employed a microgear wheel fabricated with the cut and refill technique. Rotation rate is measured by a magnetoresistant sensor that uses Permalloy to relay information from the microdynamic gear wheel system. This system is a noncontact transducer. It has the advantage of reduced frictional drag on the moving parts and should be highly reliable.

An ensemble of magnetoresistive sensor arrays with a non-contact transducer transforms the rotor rotation rate into an electrical signal. Two Wheatstone bridge sensors are arranged to improved capability by measuring both X and Y components of the field at the same point. Both sensors are full Wheatstone configurations with four active resistors in the middle of the sensitive structure and four shielded reference resistors. The sensing resistors are located between flux concentrators in order to direct the magnetic field and generate an electric signal.

In the end, our goal is to obtain an accurate, fast system that is easy to use.

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