Nav: Home

NIST goes with the (slow) flow: New technique could improve biotech, precision medicine

September 26, 2019

Researchers at the National Institute of Standards and Technology (NIST) have developed an optical system that accurately measures the flow of extraordinarily tiny amounts of liquids -- as small as 10 billionths of a liter (nanoliters) per minute.

At that rate, it would take a liter bottle of water about 190 years to drain. (A single drop of water contains 50,000 nanoliters.) The new measurements are a major improvement over technology the NIST team reported in 2018.

Precisely measuring and controlling minuscule flow rates has become critically important in the burgeoning field of microfluidics, which includes the delivery of minute amounts of drugs, the preparation of tiny amounts of liquids, the formation of microdroplets and biotechnology studies that monitor the flow of nutrients to cells. In treating cancer and other diseases, drug-delivery pumps dispense as little as tens of nanoliters (nL) per minute into the bloodstream. That flow must be extremely precise so that the total dosage the patient receives is exactly what the physician prescribed.

Low rates of flow also play a role in separating a mixture into its chemical constituents based on how slowly they travel through a gel or another medium.

The new method relies on a single laser that shines on light-sensitive molecules in a liquid flowing through a microchannel -- a silicone pipe or tube about the diameter of a human hair. The interaction of the laser light with the molecules depends on the rate of flow of the liquid.

If the fluid is flowing relatively rapidly through the microchannel, the laser simply causes the light-sensitive molecules to shine or fluoresce. But for liquids that flow more slowly and are therefore exposed to the laser light for a longer time, the story is more complex: After a certain amount of light hits the molecules, they burn out and no longer fluoresce. Thus, the slower the flow, the greater the number of light-sensitive molecules that are extinguished and the dimmer the fluorescence.

The team calibrated their measurements by comparing them with measurements of much higher rates of flow recorded by established flow meters, which do not require a laser.

Greg Cooksey, Paul Patrone and their NIST colleagues, along with a NIST summer undergraduate research fellow from Montgomery College in Germantown, Maryland, reported the findings in a recent issue of Analytical Chemistry. The study follows up on a Physical Review Applied paper describing the theoretical proof, of the method.

A key advantage of the new method is that the flow measurements are independent of the size and shape of the channel through which the fluid is traveling. The new method is an offshoot of a previous system developed by the NIST team, which required knowledge of the geometry of the channel and laser intensity, adding considerable uncertainties in the measurements.

The new method is sensitive enough to determine the very slowest rate of flow that can actually be measured for a given experimental setup. Below this rate, the random motion of particles in all directions -- diffusion -- confounds measurements of the orderly flow of particles.

The lowest rate of flow that could be distinguished from diffusion was 0.2 nL, or 200 trillionths of a liter per minute. Precise determination of this limit, known as zero flow, allows researchers to control flow rates more precisely than they can be measured. The NIST team is now experimenting with using larger molecules, which diffuse more slowly, and narrower channels, to enhance the ability to discriminate ordinary flow from random diffusion.

The team also reported that it could control a rate of flow as small as 2 nL per minute, with an uncertainty of just 5%.

The measurement method provides several potential opportunities for spinoff technologies and may enable manufacturers of microfluidic devices to develop a new generation of flow sensors, Cooksey said. The team has submitted a patent application on the technique. Overall, better flow measurement leads to improvements in the precision of chemical sensing instruments and safety of drug-delivery devices.

The new method of measuring low flow rates is directly related to one of NIST's key programs, NIST on a Chip. The program aims to develop a suite of accurate, quantum-based measurement technologies intended to be deployed nearly anywhere and anytime, without a manufacturer having to halt production while a sensor or other device is shipped to NIST for calibration. The new microflow measurement system could help dispense precise amounts of microfluids used in a host of NIST on a Chip technologies.

G.A. Cooksey, P.N. Patrone, J.R. Hands, S.E. Meek, A.J. Kearsley. Dynamic Measurement of Nanoflows: Realization of an Optofluidic Flow Meter to the Nanoliter-per-Minute Scale. Analytical Chemistry. Published online August 8, 2019. DOI: 10.1021/acs.analchem.9b02056

P.N. Patrone, G.A. Cooksey, A.J. Kearsley. Dynamic Measurement of Nanoflows: Analysis and Theory of an Optofluidic Flowmeter. Physical Review Applied. Published March 11, 2019. DOI: 10.1103/PhysRevApplied.11.034025

National Institute of Standards and Technology (NIST)

Related Laser Articles:

A laser for penetrating waves
The 'Landau-level laser' is an exciting concept for an unusual radiation source.
Laser light detects tumors
A team of researchers from Jena presents a groundbreaking new method for the rapid, gentle and reliable detection of tumors with laser light.
The first laser radio transmitter
For the first time, researchers at Harvard School of Engineering have used a laser as a radio transmitter and receiver, paving the way for towards ultra-high-speed Wi-Fi and new types of hybrid electronic-photonic devices.
The random anti-laser
Scientists at TU Wien have found a way to build the 'opposite' of a laser -- a device that absorbs a specific light wave perfectly.
Laser 'drill' sets a new world record in laser-driven electron acceleration
Combining a first laser pulse to heat up and 'drill' through a plasma, and another to accelerate electrons to incredibly high energies in just tens of centimeters, scientists have nearly doubled the previous record for laser-driven particle acceleration at Berkeley Lab's BELLA Center.
Laser physics: Transformation through light
Laser physicists have taken snapshots of how C60 carbon molecules react to extremely short pulses of intense infrared light.
Laser-induced graphene gets tough, with help
Laser-induced graphene created at Rice University combines with many materials to make tough, conductive composites for wearable electronics, anti-icing, antimicrobial applications, sensors and water treatment.
How molecules teeter in a laser field
When molecules interact with the oscillating field of a laser, an instantaneous, time-dependent dipole is induced.
Laser blasting antimatter into existence
Antimatter is an exotic material that vaporizes when it contacts regular matter.
New laser advances
Lasers are poised to take another step forward: Researchers at Case Western Reserve University, in collaboration with partners around the world, have been able to control the direction of a laser's output beam by applying external voltage.
More Laser News and Laser Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at