Ron L. Bardell

Lab-on-a-chip for drug development

Significant advances have been made in the development of micro-scale technologies for biomedical and drug discovery applications. The first generation of microfluidics-based analytical devices have been designed and are already functional. Microfluidic devices offer unique advantages in sample handling, reagent mixing, separation, and detection. We introduce and review microfluidic concepts, microconstruction techniques, and methods such as flow-injection analysis, electrokinesis, and cell manipulation. Advances in micro-device technology for proteomics, sample preconditioning, immunoassays, electrospray ionization mass spectrometry, and polymerase chain reaction are also reviewed.

Microfluidic technologies in clinical diagnostics

BACKGROUND Laboratory instrumentation and analytical devices are becoming smaller, simpler, and smarter. This trend to miniaturization extends to fluid handling and fluid analysis. However, fluid behavior undergoes significant changes as geometric scale decreases. The laminar flow behavior of fluids in microfluidic devices must be accommodated in the design and development of clinical and bio-clinical miniaturized systems. CONCLUSION The scale of chemical and clinical analysis systems will continue to decrease. The capability to manufacture smaller fluidic devices and to quantitatively monitor smaller volumes of liquids bring this process of miniaturization into the domain of laminar flow. New and enabling technologies are being developed using the unique diffusion-based characteristics of the laminar flow domain for sample preparation and analysis. These new analytical systems will have a significant impact on the future of clinical diagnostics.

Microfluidic disposables for cellular and chemical detection: CFD model results and fluidic verification experiments

Micronics has developed a wide variety of microfluidic devices and integrated systems for clinical diagnostics and life sciences applications. They fall into two general classes: machine-controlled disposable cartridges, and passive self-contained disposable cards. They include particle separators, flow cytometers, valves, detection channels, mixers, and diluters. Current applications for these devices include a hematology analyzer, stand-alone blood plasma separators, and a variety of chemical and biological assays. In this paper, we will focus on microfluidic structures for chemical and cellular analysis. Experimental data as well as the results of fluid modeling will be shown.

Development of an evaporation-based microfluidic sample concentrator

MicroPlumbers Microsciences LLC, has developed a relatively simple concentrator device based on isothermal evaporation. The device allows for rapid concentration of dissolved or dispersed substances or microorganisms (e.g. bacteria, viruses, proteins, toxins, enzymes, antibodies, etc.) under conditions gentle enough to preserve their specific activity or viability. It is capable of removing of 0.8 ml of water per minute at 37°C, and has dimensions compatible with typical microfluidic devices. The concentrator can be used as a stand-alone device or integrated into various processes and analytical instruments, substantially increasing their sensitivity while decreasing processing time. The evaporative concentrator can find applications in many areas such as biothreat detection, environmental monitoring, forensic medicine, pathogen analysis, and agricultural industrial monitoring. In our presentation, we describe the design, fabrication, and testing of the concentrator. We discuss multiphysics simulations of the heat and mass transport in the device that we used to select the design of the concentrator and the protocol of performance testing. We present the results of experiments evaluating water removal performance.

Passive Microfluidics — Ultra-Low-Cost Plastic Disposable Lab-on-a-Chips

A number of microfluidic devices have been developed that do not require any external power source or means for fluid movement. They include particle separators, valves, detection channels, mixers, and diluters. Current applications for these devices include standalone blood plasma separators, and a variety of qualitative and semi-quantitative assays. Experimental data as well as the results of fluid modeling are shown.

Well-Plate Formats and Microfluidics — Applications of Laminar Fluid Diffusion Interfaces to HTP Screening

Microfluidic disposables are presented that are compatible with standard well plate readers and robotic filling systems. The disposables perform extractions and sample cleanup procedures using the diffusion-based separation principle.

Impedances for Design of Microfluidic Systems

System analysis is essential for accurate design of complex microfluidic systems. For instance, lumped-parameter system models of micropumps with no-moving-parts (NMP) valves need fluid elements that represent the separated, oscillating, laminar flow that occurs in these valves. No experimental or analytical method is currently available to determine the impedance of this type of flow. A numerical method for deriving NMP valve impedance has been developed, based on an extension of analytical methods for channels of non-varying cross-section. The resistance and inertance calculated are 20% lower than for a straight rectangular channel of equivalent length.

Enabling Technologies for a Personal Flow Cytometer, Part II: Integrated Analysis Cartridges

A novel microcytometry system that monitors leukocyte populations to assess human pathogen exposure is being jointly developed by Micronics and Honeywell. The system contains both an instrument and a disposable card that contains complex microfluidic circuits for blood sample acquisition, reagent storage, erythrocyte lysis, cytometry, and waste storage. This talk discusses the subsystems that provide these functions and shows experimental results qualitatively describing hydrodynamic focusing and leukocyte populations.

Modeling of microscale processes as a tool to speed development and enhance performance of microanalytical products

With macroscopic chemical analysis devices, it is usually possible during the development phase to mount flow sensors, temperature probes, and optical detectors at various positions along the instrument pathway to experimentally determine the optimum operational parameters for the device. This approach usually fails for microdevices as standard sensors and probes are typically of the same scale as the microdevice. These relatively large sensors interfere so much with the experiments that any results generated do not represent the actual performance of the system. Fortunately, modeling of microscale processes provides a uniquely useful tool to develop microanalytical devices and optimize their operational parameters, since the chemical and physical processes in the microscale generally follow deterministic physical laws that can be accurately represented in mathematical models. We will discuss some of the methods used to model and design microanalytical assays based on these principles, as well as several ongoing development projects that MicroPlumbers is currently involved in (including a clinical microsensor, a microvolume blood collection device, and a novel clinical assay), and show how modeling and rational design is used during the development processes and yield devices with optimized performance.

New Assays Based on Laminar Fluid Diffusion Interfaces—Results from Prototype and Product Testing

Central to Micronics’ microfluidics technology platforms is the generation and use of Laminar Fluid Diffusion Interfaces (LFDIs). One of the embodiments of LFDIs is in diffusion-based detection technology, which is based on the parallel flow of individual streams in a single microfluidic channel. Micronics’ T-Sensor® based Chemical Analysis System (CAS) harnesses diffusion to identify unknown concentrations of chemical species, allowing researchers to perform multiple assays on a single version of a disposable microfluidic cartridge. Implementations of both a prototype portable device and a benchtop system are demonstrated, with CV’s ranging from 2.6 to 10%.