Biomicrofluidics - The Flow

Micro-Centrifuges Provide Lab-On-A-Chip Functionality

2011-07-25T16:14:49Z

To enable the rapid point-of-care analysis promised by "lab on a chip" technology, doctors need the whole lab. Previous efforts to design lab-on-a-chip systems have managed to shrink the devices used to gather medically relevant data, but have failed to replicate the beakers, pipettes and various tools that transform biological samples into usable forms. Utilizing the propensity of plastic to deform under stress, a team of Taiwanese scientists has figured out how to make a centrifuge small enough to work in lab-on-a-chip situations.

The Taiwanese-designed centrifuge works mechanically and has few moving parts, making large scale industrial scale production easier than other similar solutions. By combining the ability to separate blood plasma at very small volumes with a practical, cheap design, these micro-centrifuges aim directly for the medical device market, as opposed to other, more complex and theoretical, lab-on-a-chip devices.

"Therefore, a simple, robust, and affordably manufacture-able decanting method is desired. In this study, we present a novel approach to decant supernatant by manipulating the centrifugally induced pressure and the elastic behavior of the plastic lids of the chamber," said the recent paper in the journal Biomicrofluidics discussing the centrifuges.

The paper, titled "Supernatant decanting on a centrifugal platform," details how the entire process relies on the fact that the plastic deforms faster than blood cells and blood plasma can mix.

The spin cycle beings with the centrifuge spinning up towards its maximum speed of 4,000 rpm. During this initial period, centrifugal force pulls the sample out of its reservoir chamber and into the first part of the two section decanting chamber. The wall separating the two sections of the decanting chamber is short enough for liquids to flow from the first section to the next section when at rest, but too tall for the liquids to cross during the spin cycle.

When the centrifuge reaches its maximum speed of 4000 rpm, the blood cells and the blood plasma separate as in a standard centrifuge. However, since the volume of the plastic container has expanded under the stress of spinning, both liquids remain pulled beneath the lip of the first section of the decanting chamber.

As the spin cycle slows down and ends, the decanting chamber returns to its original shape, pushing the liquid over the wall and into the second section of the decanting chamber. Since spinning had divided the liquid plasma from the blood cells, only the plasma flows into the second part of the decanting chamber, effectively separating the two constituents for analysis.

The available spin speed and the mechanical properties of the materials needing separation dictate the size and shape of the chambers. Although the authors of the Biomicrofluidics paper focused on medical applications, and shaped their chambers to separate blood plasma, this method could provide lab-on-a-chip centrifugal separation for any mixture in any field. Far from an exclusively medical advance, these centrifuges could parse soil samples, test water samples, or monitor the efficiency of a wide range of industrial processes.

Biomicrofuidics sees huge increase in Impact Factor to take second spot in Physics, Fluids & Plasmas

2011-07-01T20:01:32Z

Journal metrics just released by Thomson Reuters*, once again show Biomicrofluidics (BMF) rising through the ranks with a 35% increase in Impact Factor in 2010 compared to 2009. BMF’s 2010 Impact Factor is 3.896.

Other highlights of the new data include:

5-Year Impact Factor

BMF’s 5-year impact factor, a number that gives a broad view of citation activity over a longer time, is 3.787.

Eigenfactor Score^TM and Article Influence^TM Score

BMF’s 2010 Eigenfactor^TM Score is 0.00155 and the Article Influence^TM score is 0.894. Both are substantially higher than last year.

Impact Factor

BMF’s 2010 Impact Factor is 3.896.

Immediacy Index

The journal’s Immediacy Index is 0.855 in 2010.

Cited Half-Life

BMF’s Cited Half-Life is steady at 1.6.

The American Institute of Physics is indebted to the author and reviewer community for support of BMF. Your contributions—coupled with the dedication of our editors—are enabling BMF to become a valued resource!

*2010 Journal Citation Reports^® (Thomson Reuters, 2011)

New 3-D tumor model a step toward speeding cancer drug research

2011-06-08T18:14:33Z

College Park, Md. (June 08, 2011) - A team of scientists has developed a way to coax tumor cells in the lab to grow into 3-D spheres. Their discovery takes advantage of an earlier technique of producing spherical cavities in a common polymer and promises more accurate tests of new cancer therapies.

As team leader Michael R. King, Ph.D., of Cornell University explains, "Sometimes engineering research tends to be a case of a hammer looking for a nail. We knew our previous discovery was new and it was cool. And now we know it's useful."

Three years ago, the team -- in collaboration with Lisa DeLouise, Ph.D., MPD, of Rochester, N.Y. -- perfected a low-cost, easy fabrication technique to make spherical cavities in PDMS (polydimethylsiloxane), a widely used silicon organic polymer. More recently, the Cornell team discovered that these cavities could be used as a scaffolding to grow numerous tumor spheroids, which could serve as realistic models for cancer cells. The Cornell team's work appears in the current issue of Biomicrofluidics, a publication of the American Institute of Physics.

The three-dimensional spheroids hold the potential to speed cancer drug discovery by providing a realistic and easily accessible substrate on which to test drugs. Their 3-D nature is an asset because in the body, tumor cells grow in 3-D--yet most laboratory studies of cancer have been done in 2-D, with a single layer of cancer cells grown on the bottom of a petri dish. Too often a promising 2-D drug candidate fails when it enters the 3-D stage of animal testing. The new 3-D tumor spheroids may help eliminate that problem. They also offer a realistic tumor oxygen environment that cues the blood vessel growth that nourishes tumors--an appealing target for anti-cancer drug design.

"Basically, any laboratory that works with cells could adopt our new spherical microcavity system to do their own 3-D experiments or drug screening on hundreds or even thousands of little tumor spheroids," said King.

###

The article, "Continuously perfused microbubble array for 3D tumor spheroid model" by Michael R. King, Sivaprakash Agastin, Ut-Binh T. Giang, Yue Geng, and Lisa A. DeLouise appears in the journal Biomicrofluidics.

Superhydrophobic Microfluidics and the Wettability Gradient

2011-05-19T20:30:55Z

I like it when articles ask me questions. right at the beginning, i usually throw out an answer and then reading the rest of the article is like a mystery novel... Let's see what kind of guesses we can come up with for this one.

A team of researchers from Hong Kong have just published their article, "Do droplets always move following the wettability gradient?" appearing today in Applied Physics Letters, the authors look at liquids on a superhydrophobic surface. To get an idea of how hydrophobic a superhydrophobe is, check out this picture of a drop of water on a lotus leaf. The standard definition is that the contact angles of a drop of water exceeds 150° and the roll-off angle is less than 10°. Interestingly enough, this is called the Lotus Effect and has some interesting properties.

The authors summarize:

[W]e systematically investigated droplet impacting dynamics on a nonuniform superhydrophobic surface with a wettability gradient. Different from previous reports that the droplet moves toward the direction of decreasing CA, interestingly, we found that the droplet can fashion strikingly different self-migration patterns (toward or against the wettability gradient) depending on the competition of the capillary pressure and the effective water hammer pressure. Our findings highlight the importance of controlling surface roughness (wettability) and impact condition in precise manipulation of droplet placement and trajectory in microfluidics, heat transfer, and water harvesting systems.

Microfluidics for Kindergartners

2011-04-13T19:39:48Z

Michelle Khine is a biomedical engineering at UC Irvine, but in some ways she is still on the playground... teaching microfluidics with the help of children's toys.

Professor Khine likes to have fun, and from the Technology Review video posted here, it seems like her favorite toy might be Shrinky Dinks. She demonstrates her method for creating microfluidic channels and devices by using the Shrinky Dinks materials and an ink-jet printer.

The related Lab on a Chip article, "Shrinky- dink microfluidics: rapid generation of deep and rounded patterns," goes into more detail about the process and procedures involved.

Professor Khine is also founder of Shrink Nanotechnologies, a company that looks to take advantage of the flexibility and shrinkability of materials like shrinky dinks to create advances diagnostic tools.

Congratulations to the Small Matters video contest winner!

2011-02-02T16:28:34Z

Congratulations! to the Small Matters winner:

Zach Gagnon, Johns Hopkins University

Thank you to all the entrants. Check back to the Biomicrofluidics homepage for announcements on next year's contest. Winners will be announced at the 2012 AMN-APLOC meeting in Dalian, China.

View the winning entry:

Microfluidic Gradient Formation by Maxwell-Wagner Polarization at an Aqueous Electric Interface

This work integrates components from AC electrokinetics, microfluidics, and cell biology to produce tunable spatial chemical gradients in a microfluidic device for studying directed cell migration. I explore a new type of Maxwell Wagner polarization for the injection of aqueous liquid across a liquid-liquid interface. The rate of injection is tunable and used to manipulate fluid much the same way dielectrophoresis is used on bioparticles; fluid can be injected into different streamlines and passed downstream to a gradient generator only when the electric field is active. The phenomenon is used to generate and control the concentration and direction of spatial chemical gradients. Finally, the controllable gradient is used to explore directed cell migration. In particular, the social amoeba Dictyostelium discoidium is shown to respond to an induced chemical gradient by migrating from low to high concentrations of cyclic 3',5'-adenosine monophosphate (cAMP) only when the electric field is active. The end result is a new type of liquid-liquid polarization that can controllably inject fluid to create controllable microenvironments for biological studies.

Watch the video on SciVee.tv

Supplementary Materials
Maxwell Wagner Polarization at an Aqeuous Interface: Physics, Microfludics and Cell Biology (PDF)

Announcing the "Small Matters" Video Contest

2010-09-29T19:52:56Z

Biomicrofluidics is pleased to announce a video contest, Small Matters. The contest is to highlight not only the exciting scientific merit of work conducted in the area of microfluidics and nanofluidics, but also the aesthetic and artistic qualities of the science. Winning entries will demonstrate a novel scientific concept in an elegant presentation. All finalists will be published in a special section of Biomicrofluidics and one grand prize winner will be chosen to receive an iPad.

The winners of Small Matters will be selected by an esteemed panel of scientists from the Editorial Advisory Board of Biomicrofluidics. Winning entries will be announced at The Second Conference on Advances in Microfluidics and Nanofluidics in Singapore, January 2011 and will be on display for conference attendees to view.

The submission deadline to enter the contest is 1 December 2010 and must include a description of the scientific content presented in the video. Text should be no greater than 1 printed page and videos should be no longer than 5 minutes. For instructions on how to submit to the contest, please visit the contest instructions page.

Biomicrofluidics, a free to read, free to publish journal of the American Institute of Physics, hopes the community will find this contest valuable and will promote the exciting research being conducted in microfluidics and nanofludics.

Neurology On A Chip (InsideScience.org)

2010-08-17T20:31:24Z

WASHINGTON (ISNS) — Engineers and biologists at McMaster University in Hamilton, Ontario, have succeeded in coaxing tiny worms to move around a microchip using electric fields. This should help neurologists study the human nervous system.

The worms, called C. elegans, are one of the mainstays of neurological research. That’s because the worms, with only a few hundred neurons, have a simple nervous system. In the new McMaster experiment, the worms are coaxed into starting and stopping, pretty much on command.

"This technique provides us for the first time the ability to communicate with the worms and make them do a certain task" said Ravi Selvaganapathy, an engineer at McMaster. "For instance, we could expose the worm to a drug and quantitatively measure the speed of the worm and compare it to unexposed worms."

Previously worms could be made to move, but not in any reliable, repeatable way. Getting the worms to move in a definite way gives scientists a chance to be more precise in measuring the effect of various toxins or remedies.

C. elegans worms are used to study human illnesses because 60 percent of the genes in their cells have a human equivalent. They can suffer conditions similar to human diseases such as Parkinsonism and Huntington’s diseases. In the worms’ accelerated lifespan these diseases can play out in days rather than decades.

The ability to get the worms to respond to electric current solves the problem moving them to the right place at the right time, such as to receive a certain supply of nutrient. Some alternative methods of coaxing such as offering food or shining ultraviolet light on them can take too long to work.

The McMaster researchers, publishing their work in a recent issue of the journal Applied Physics Letters, hope to have the chance to observe up to a thousand worms at a time on a single platform, each moving in its own narrow channel. This will allow a quicker and more detailed look at reactions to a variety of drugs, chemicals, and nanoparticles. This will also help in studying the course of diseases such as obesity and hypertension.

Read the full article in Applied Physics Letters.
This story was written and published on the ISNS news site.
Applied Physics Letters is published by the American Institute of Physics, which also publishes Inside Science News Service.

Electrical Properties of Blood Help Diagnose Disease

2010-07-14T00:09:25Z

For decades, the electrical properties of human blood have been of interest in a wide range of biomedical applications, such as in radiofrequency hyperthermia, body composition, electrocardiography, and the diagnosis and treatment of various physiological conditions.

In a recent article published in Biomicrofluidics, researchers at King Abdulaziz University in Saudi Arabia have published a study of the electrical and mechanical (viscosity) properties of blood and the effects of electrical conduction on its microstructure. The authors use many parameters in their research and conclusions, including the relaxation time of micro-cells, molecules, bacteria, protein, hormones, glucose, chemicals, vitamins, and antibodies, which all greatly influence the chemical and physical character of blood.

Abdalla, S., Al-ameer, S., & Al-Magaishi, S. (2010). Electrical properties with relaxation through human blood Biomicrofluidics, 4 (3) DOI: 10.1063/1.3458908

Teaching Jell-O Microfluidics

2010-06-25T17:41:27Z

One of the tastiest things I can think of is Jell-O—and just in time to celebrate the Second Annual Jell-O Mold Competition, comes a bit of research from the ACS journal, Analytical Chemistry.

The article, "Using Inexpensive Jell-O Chips for Hands-On Microfluidics Education¹," presents an interesting model of microfluidic devices using, you guessed it, Jell-O.

The idea is to get anyone (probably mostly Jell-O enthusiasts) really excited about microfluidics. Getting students to design and build a microfluidic device could spark an immense interest in a technology that could one day be as commonplace as cellphones.

This figure at right shows the authors' scheme for "producing Jell-O chips using soft lithography," whose hopes are they certain key concepts—including photolithography, crosslinking density, photopolymerization, and rapid prototyping—will be easily conveyed to students of all levels. The article runs through a few different chip designs, including one that demonstrates pressure-driven flow, another that teaches principles of dimensionless numbers, and finally a "Jell-O chip" that can be used for teaching the fundamentals of pH sensing and parallelization,

This isn't explicitly mentioned, but I'm hoping the authors take into account how hungry the students are before proceeding with additional lessons... at the end of the day, there might not be enough Jell-O to go around.

¹Yang, C., Ouellet, E., & Lagally, E. (2010). Using Inexpensive Jell-O Chips for Hands-On Microfluidics Education Analytical Chemistry DOI: 10.1021/ac902926x

Biomicrofluidics Sees Significant Increase to Impact Factor

2010-06-18T16:21:35Z

In its second year being tracked by Thomas Reuters Science Edition of Journal Citation Reports (JCR), Biomicrofluidics (BMF) saw a substantial jump in Impact Factor to 2.895, bringing it in to the top 5 in Fluids and Plasmas Physics.

Not only did the journal see a dramatic improvement in Impact Factor, but under the leadership of co-editors Hseuh-Chia Chang and Leslie Y. Yeo, the journal continues to increase the number of articles it is publishing. The Journal is rapidly becoming a must-read for the community.

Other impressive metrics for Biomicrofluidics include:

Immediacy Index: Increase of 182% bringing it to an impressive 1.059!

EigenFactor Score: Increase of 53% bringing the score to 0.00049!

Chaotic Behavior in Liquids

2010-06-16T19:12:01Z

An interesting video was posted just today. The subject is Lagrangian Coherent Structures (LCS) and the Gulf Coast oil spill with Thomas Peacock, an Associate Professor of Chemistry at MIT.

Dr. Peacock curated and edited a Chaos Focus Issue on LCS in Fluid Flows and is studying how and where the oil spill along the Gulf Coast will come ashore.

And who's that mysterious host? In the interest of full disclosure his name is: me!

Thomas Peacock, MIT Discusses LCS and the Gulf Oil Spill from AIP Journals published on June 16, 2010.

The Great Divide in Microfluidics

2010-05-19T22:32:03Z

Nature Methods has been around for a few years now but I always sort of forget about them for some reason. Well, luckily I read what Google tells me to and not what my lousy memory tells me to.

So I was pleasantly surprised to read this feature story by Nature Method's technology editor, Nathan Blow. Dr. Blow presents a lovely and easy to read overview of what he calls "The great divide" between the intricate and sophisticated microfluidic devices that are created in laboratories and the small number of commercially available products.

The piece really speaks for itself and the community, so there's not much to add, except it's good to see that this great divide is narrowing a bit.

A Non-Profit Biotech for Global Health

2010-05-13T22:29:10Z

When people talk about microfluidic devices and their potential applications, they always talk about the cheapness and portability of viral detection and delivery devices. There always is an undercurrent, though, of startups, price points, and giant companies being used for distribution and sales. This isn't necessarily a bad thing, but such an important and potentially life-saving technology doesn't need to be so tightly controlled by those with the biggest financial interests.

That's one reason it's so uplifting to find out about Diagnostics for All—a non-profit organization that is trying to bring lab-on-a-chip technologies to parts of the world that may not be able to afford it. The company uses a patterned paper platform for their diagnostic devices. From the site:

To fabricate a diagnostic device, DFA patterns channels and assay zones (or wells) of water-repellent materials into a piece of paper roughly the size of a postage stamp. Biological and chemical assay reagents are then deposited in the wells. When blood, urine, saliva, sweat or other biological samples are applied to the device, the paper wicks the sample through the channels to the assay zones, without external pumps or power. Upon contact, the assay zone quickly changes color and results are then easily read by comparing the color change with a reference scale printed on the device. After use, the device can be easily disposed of by burning. As we develop more advanced diagnostics, DFA's paper devices can be embedded with electrical circuitry to enable resistive heating, electrochemical assays, or initial processing of assay results.

And the reason this project—started in 2007 by Harvard's George Whitesides—is gaining attention now is because the company announced this week that it has just received a $100,000 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation. The grant is "designed to support a global health research project for the diagnosis of HIV in Third World countries."

Just the fact that this kind of hybrid biotech/non-profit company can exist and gain support from someone as influential and charitable as the Bill & Melinda Gates Foundation serves to remind the research community of the real importance of their work—saving lives.

Building A Handheld HIV Detector

2010-04-28T19:26:25Z

Researchers race to bring cheap HIV testing to rural regions of developing countries.

This story originally appeared at Inside Science News Service, and is republished here with permission.

By Devin Powell, Inside Science News Service

This thin-section transmission electron micrograph (TEM) depicted the ultrastructural details of a number of "human immunodeficiency virus" (HIV) virus particles, or virions.

Credit: CDC.gov | Cynthia Goldsmith
Rights Information

PORTLAND, Ore. (ISNS) -- Most Africans infected with HIV live in rural areas, where access to HIV testing has lagged behind the growing availability of HIV-fighting drugs.

Only clinics in big cities can afford the blood work equipment that allows doctors to monitor the disease's progression and treat it early and effectively. Doctors in rural areas often prescribe treatment based only on the visible symptoms their patients show.

Responding to this need, researchers at California company Palo Alto Research Center have shrunk the laser technology inside large laboratory machines down to about the size of an iPod. Their cheap, handheld device promises to provide an immune system check-up on the spot and in less than 10 minutes.

"You need a device that a health worker can put into a backpack to reach the people in Africa or Asia," said Peter Kiesel, who presented his team's battery-powered prototype at a recent meeting of the American Physical Society in Portland, Ore.

The technology analyzes a small sample of blood drawn by a finger prick. Blood cells flow through a tiny channel, illuminated by a laser beam. A detector watches patterns in the light that bounces off the cells to identify them.

The detector looks for and counts CD4+ T cells, cells in the immune system that are killed by the HIV virus. The World Health Organization recommends that antiretroviral treatment begin when a patient's CD4 count drops below 250.

"The quality of their test is great," said researcher Bernhard Weigl of PATH, a non-profit reviewing a variety of CD4 testing technologies. "If you look at their graph, it pretty much looked like the graph you would get from a big instrument."

PARC's prototype cost about $250 to build, a hundred times cheaper than the large flow cytometers currently in use. Still, getting it to market may prove challenging.

Kiesel is competing against a dozen other groups vying to fill the need for cheap, portable CD4 tests. Other technologies have been under development for years, including a half-dozen recent projects funded by the Bill and Melinda Gates Foundation that include disposable CD4 tester kits as easy to use as a home pregnancy test. Kiesler's laboratory-tested device is a couple of years behind these projects, some of which have been tested in the field in African countries.

None of these devices is currently on the market. Many have been redesigned several times in the quest for commercialization, including a device by the Austin-based biotech company LabNow, which had hoped to have its technology on the market by 2006.

In the end, Weigl suspects that health workers will use some combination of these approaches in the field. Detectors like the one at PARC, with a low cost per person tested, make sense for areas with many cases of HIV, said Weigl. But disposable kits, which cost less initially and require no maintenance, may be a good solution for remote areas with fewer cases.

"I would be surprised if the first technologies aren't out by 2012," said Weigl. "The market is big; you're looking at many millions of users that have to get checked up every few months."