Microfluidics is the combination of science and technology employed to investigate microliter to nanoliter quantities of complex fluids (multi-component mixtures, colloids, cell suspensions, nanoparticle suspensions, biomolecules, biofluids such as blood, etc.) localized within channels that have diameters on the order of tens to several hundreds of micrometers. For reference, a human hair is about 100 µm wide, while a single drop of water is approximately 50 microliters. The combination of accurate measurements with the chip-scale implementation enabled by microfluidics is a natural area of interest for the NIST-on-a-Chip program.
Microfluidics has become a fundamental tool enabling a wide range of measurements and applications from medical diagnostics, molecular biology, genetics, and pharmaceuticals to biophysics, chemistry, nanotechnology, and engineering. The primary apparatus consists of micro-channels that range from millimeters to centimeters in size embedded in silicon, glass, or polymers. The channels can be used to precisely control flow of a single liquid component (e.g. a drug) or be organized into complex networks that facilitate high-speed assays of large arrays of substances (e.g. a gene expression or drug discovery tool). Many microfluidic devices include sensors that have electrical inputs and outputs, as well as photonic sensors. In addition, NIST scientists are exploring ways in which microfluidic systems can be integrated with microelectromechanical systems (MEMS) with feature sizes that can reach nanometer scale.
In this rapidly-evolving field, there is a growing demand for standards for traceable measurements, enabling reproducibility of results from device to device as well as device interoperability. Meeting that need will require development of new technologies, device control methods, and embedded sensors, among other innovations. To address these needs, NIST researchers are working to:
- Support the development, manufacture, and reliability of sensors used in microfluidic devices, and improve the reproducibility of flow measurements.
- Advance measurements of flow, viscosity, permittivity, pressure, and temperature in chip-scale sensors.
- Devise NIST-traceable primary sensors that can be deployed in microfluidic devices at the user’s location.
- Develop a “common platform” for interfacing different measurand sensors or producing “plug and play” microfluidic sensors that measure multiple properties at once.
- Facilitate communication between developers and users of microfluidic devices in academia, government research, and industry via publications and seminars on 1) design, 2) fabrication techniques, 3) applications, and 4) the physics of microfluidic devices.
- Collaborate with partners to patent and license new sensor designs.
Measurements using microfluidic approaches are particularly amenable to analyzing the behavior of complex fluids, whose physical properties can vary greatly depending on the details of the composition (i.e. size, shape, and concentration of nanoparticles in a suspension, interactions of biomolecules or colloidal particles, miscibility of multi-component fluids, etc.). Furthermore, the small, compact nature of microfluidic-based measurements, the potential for high throughput and high levels of integration, and the drastic reduction in sample volume required can enable a wide variety of applications, including:
- Point-of-care diagnostics in clinical health care, such as blood or breath testing.
- Biomolecular or chemical detection.
- Separations of mixtures.
- Multiplexed testing of multiple properties of large arrays of samples for life sciences, medicine, and pharmaceuticals.
- Quality control, manufacturing, and design of materials.
- Precision implantable devices such as an artificial pancreas, and chip-scale infusion pumps for various pharmaceuticals, as well as implantable dissolvable devices.
In order to develop accurate on-chip measurements of physical fluid properties, it is often necessary to measure the rate and nature of flow at the microscale, and to develop compact, fast sensors to detect the fluid properties of interest. The end goal is to integrate multiple measurements of physical properties together to provide rapid, comprehensive, multi-modal data on the physical fluid properties of complex fluids. Our research program focuses on the fundamental issues (including traceable measurements, device development, and integration) needed to enable high-throughput, multimodal measurements.
Quantifying and controlling flow at the microscale enables the precise control of fluid movement on-chip necessary for accurate quantitative measurements. Beyond flow, microscale devices lend themselves to rapid, accurate measurements of viscosity and rheological properties of complex fluids.
The development of compact optical and electromagnetic sensors is a key step in developing on-chip measurement capabilities. While a wide variety of quantities can potentially be measured, many issues such as accuracy, calibration, reproducibility, and sensitivity must be carefully addressed for such measurements to deliver in a high-throughput, compact on-chip environment.
The integration of multiple measurement modalities into a single chip or chip-based package will enable accurate, multi-parameter data to be obtained on a wide variety of complex fluids. The choice of sensors, and the ability to integrate such sensors with stable and controllable flow and temperature, can depend on the details of the specific fluid under investigation.