NIST scientists are developing next-generation microfluidics devices that can rapidly and accurately measure and control flow and pressure of biological and other kinds of fluids in extremely small volumes. Teams have developed standards that measure flows of 1 µL per minute with an uncertainty of less than 1% and are pushing toward ever smaller values.
Other NIST projects are devising chip-scale methods of measuring how properties such as pH and temperature affect the behavior of protein solutions or clusters of antibodies. These devices use pressure sources to drive fluids through microcapillaries and record the flow under different conditions.
Another priority goal is development of a variety of novel sensor technologies and modalities to analyze fluid properties. NIST teams are focused on finding more accurate, high-resolution ways to characterize the behavior of viscous (thick) and semisolid fluids using light beams, advanced microscopy, hologram images of suspended particles, and more.
Finally, NIST scientists are making groundbreaking progress on providing much-needed calibration standards for instruments and procedures to ensure that microfluidic measurements made in different laboratories are reproducible and comparable.
NIST scientists are improving on NIST’s dynamic gravimetric micro-flow standard, which currently provides calibrations of flow, usually of thermal flow meters. These devices track how much heat a moving fluid absorbs from a heater in the channel: The slower the flow, the more the fluid heats up. The standard provides a stable reference with documented levels of uncertainty for evaluating the accuracy and long-term stability of existing, commercially available flow meters. It also allows NIST researchers to test their new flow meter designs.
Other innovations can make possible measurements that are now extremely difficult or impossible. For example, one design uses light to track the changing position of particles suspended in liquid to determine their velocity. That method is more accurate at lower flow rates and can also be used to precisely determine zero flow.
In another example, NIST research will likely prove vitally important for fully understanding how many biological fluids (such as blood) respond to mechanical stresses. These fluids are more complex than water, which displays the same viscosity regardless of the level of mechanical stress. NIST researchers are devising novel chip-scale sensors to measure the fine-scale details of blood coagulation, the clumping of antibodies that fight infection, and other medically important properties — information not fully available at present.
Many of today’s sophisticated drugs must be delivered at specific ultra-small doses, with very narrow margins of error. Many manufacturing processes demand that tiny amounts of fluids be mixed in extremely precise ratios under carefully controlled conditions. And many important discoveries in industrial chemistry and pharmaceutical research often result from evaluating scores of combinations of different test ingredients that flow together in nL quantities. Any improvements in those techniques can have a substantial near-term impact.
In addition, many of NIST’s emerging microfluidic technologies will find their way into a new form of medical testing called “point of care” (POC) diagnostics. Instead of sending large samples of blood or other fluids off to a laboratory, a health care worker could apply chip-scale sensors directly to patients in the clinic and obtain results almost immediately. A few POC devices are already in use for blood-sugar monitoring, drug detection, immune-system monitoring and other applications. The worldwide market is expected to expand rapidly.
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