Tag Archives: lab-on-a-chip

Using acoustic waves to move fluids at the nanoscale

A Nov. 14, 2016 news item on ScienceDaily describes research that could lead to applications useful for ‘lab-on-a-chip’ operations,

A team of mechanical engineers at the University of California San Diego [UCSD] has successfully used acoustic waves to move fluids through small channels at the nanoscale. The breakthrough is a first step toward the manufacturing of small, portable devices that could be used for drug discovery and microrobotics applications. The devices could be integrated in a lab on a chip to sort cells, move liquids, manipulate particles and sense other biological components. For example, it could be used to filter a wide range of particles, such as bacteria, to conduct rapid diagnosis.

A Nov. 14, 2016 UCSD news release (also on EurrekAlert), which originated the news item, provides more information,

The researchers detail their findings in the Nov. 14 issue of Advanced Functional Materials. This is the first time that surface acoustic waves have been used at the nanoscale.

The field of nanofluidics has long struggled with moving fluids within channels that are 1000 times smaller than the width of a hair, said James Friend, a professor and materials science expert at the Jacobs School of Engineering at UC San Diego. Current methods require bulky and expensive equipment as well as high temperatures. Moving fluid out of a channel that’s just a few nanometers high requires pressures of 1 megaPascal, or the equivalent of 10 atmospheres.

Researchers led by Friend had tried to use acoustic waves to move the fluids along at the nano scale for several years. They also wanted to do this with a device that could be manufactured at room temperature.

After a year of experimenting, post-doctoral researcher Morteza Miansari, now at Stanford, was able to build a device made of lithium niobate with nanoscale channels where fluids can be moved by surface acoustic waves. This was made possible by a new method Miansari developed to bond the material to itself at room temperature.  The fabrication method can be easily scaled up, which would lower manufacturing costs. Building one device would cost $1000 but building 100,000 would drive the price down to $1 each.

The device is compatible with biological materials, cells and molecules.

Researchers used acoustic waves with a frequency of 20 megaHertz to manipulate fluids, droplets and particles in nanoslits that are 50 to 250 nanometers tall. To fill the channels, researchers applied the acoustic waves in the same direction as the fluid moving into the channels. To drain the channels, the sound waves were applied in the opposite direction.

By changing the height of the channels, the device could be used to filter a wide range of particles, down to large biomolecules such as siRNA, which would not fit in the slits. Essentially, the acoustic waves would drive fluids containing the particles into these channels. But while the fluid would go through, the particles would be left behind and form a dry mass. This could be used for rapid diagnosis in the field.

Here’s a link to and a citation for the paper,

Acoustic Nanofluidics via Room-Temperature Lithium Niobate Bonding: A Platform for Actuation and Manipulation of Nanoconfined Fluids and Particles by Morteza Miansari and James R. Friend. Advanced Functional Materials DOI: 10.1002/adfm.201602425 Version of Record online: 20 SEP 2016
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

They do have an animation sequence illustrating the work but it could be considered suggestive and is, weirdly, silent,

 

 

Faster predictive toxicology of nanomaterials

As more nanotechnology-enabled products make their way to the market and concerns rise regarding safety, scientists work to find better ways of assessing and predicting the safety of these materials, from an Aug. 13, 2016 news item on Nanowerk,

UCLA [University of California at Los Angeles] researchers have designed a laboratory test that uses microchip technology to predict how potentially hazardous nanomaterials could be.

According to UCLA professor Huan Meng, certain engineered nanomaterials, such as non-purified carbon nanotubes that are used to strengthen commercial products, could have the potential to injure the lungs if inhaled during the manufacturing process. The new test he helped develop could be used to analyze the extent of the potential hazard.

An Aug. 12, 2016 UCLA news release, which originated the news item, expands on the theme,

The same test could also be used to identify biological biomarkers that can help scientists and doctors detect cancer and infectious diseases. Currently, scientists identify those biomarkers using other tests; one of the most common is called enzyme-linked immunosorbent assay, or ELISA. But the new platform, which is called semiconductor electronic label-free assay, or SELFA, costs less and is faster and more accurate, according to research published in the journal Scientific Reports.

The study was led by Meng, a UCLA assistant adjunct professor of medicine, and Chi On Chui, a UCLA associate professor of electrical engineering and bioengineering.

ELISA has been used by scientists for decades to analyze biological samples — for example, to detect whether epithelial cells in the lungs that have been exposed to nanomaterials are inflamed. But ELISA must be performed in a laboratory setting by skilled technicians, and a single test can cost roughly $700 and take five to seven days to process.

In contrast, SELFA uses microchip technology to analyze samples. The test can take between 30 minutes and two hours and, according to the UCLA researchers, could cost just a few dollars per sample when high-volume production begins.

The SELFA chip contains a T-shaped nanowire that acts as an integrated sensor and amplifier. To analyze a sample, scientists place it on a sensor on the chip. The vertical part of the T-shaped nanowire converts the current from the molecule being analyzed, and the horizontal portion amplifies that signal to distinguish the molecule from others.

The use of the T-shaped nanowires created in Chui’s lab is a new application of a UCLA patented invention that was developed by Chui and his colleagues. The device is the first time that “lab-on-a-chip” analysis has been tested in a scenario that mimics a real-life situation.

The UCLA scientists exposed cultured lung cells to different nanomaterials and then compared their results using SELFA with results in a database of previous studies that used other testing methods.

“By measuring biomarker concentrations in the cell culture, we showed that SELFA was 100 times more sensitive than ELISA,” Meng said. “This means that not only can SELFA analyze much smaller sample sizes, but also that it can minimize false-positive test results.”

Chui said, “The results are significant because SELFA measurement allows us to predict the inflammatory potential of a range of nanomaterials inside cells and validate the prediction with cellular imaging and experiments in animals’ lungs.”

Here’s a link to and a citation for the paper,

Semiconductor Electronic Label-Free Assay for Predictive Toxicology by Yufei Mao, Kyeong-Sik Shin, Xiang Wang, Zhaoxia Ji, Huan Meng, & Chi On Chui. Scientific Reports 6, Article number: 24982 (2016) doi:10.1038/srep24982 Published online: 27 April 2016

This paper is open access.

Making lab-on-a-chip devices more accurate

An April 4, 2016 news item on phys.org announces research that will improve control and manipulation of the fluids in a lab-on-a-chip,

Lab-on-a-chip designates devices that integrate various biochemical functions on a fingernail-sized chip to enable quick and compact biological analysis or medical diagnosis by processing a small volume of biological samples, such as a drop of blood. To operate various functions on a lab-on-a-chip device, the key technology is the precise and rapid manipulation of fluid on a micro-scale.

A March 31, 2016 Pohang University of Science and Technology (POSTECH; South Korea) press release (also on EurekAlert), which originated the news item, expands on the theme,

In microfluidic devices, very small and trivial variables can frequently cause a large amount of errors. Up until now, Proportional-Integral-Derivative (PID) controller has normally been used for the manipulation of fluids in microfluidic chips. To apply the PID controller, a tedious gain-tuning process is required but the gain-tuning is a difficult process for people who are unfamiliar with control theory. Especially, in the case of controlling multiple flows, the process is extremely convoluted and frustrating.

The developed control algorithm can improve accuracy and stability of flow regulation in a microfluidic network without requiring any tuning process. With this algorithm, microfluidic flows in multiple channels can be controlled in simultaneous and independent way. The team expects that this algorithm has the potential for many applications of lab-on-a-chip devices. For example, cell culture or biological analysis, which are conducted in biology laboratories, can be performed on a microfluidic chip. Physical and chemical responses can be analyzed in the subdivided levels.

Here’s a link to and a citation for the paper,

Tuning-free controller to accurately regulate flow rates in a microfluidic network by Young Jin Heo, Junsu Kang, Min Jun Kim, & Wan Kyun Chung. Scientific Reports 6, Article number: 23273 (2016) doi:10.1038/srep23273 Published online: 18 March 2016

This is an open access paper.

Testing for antibiotic resistance in one hour

University of Toronto researchers have devised a test for antibiotic resistance which cuts down the time from up to three days to one hour. From a May 27, 2015 news item on Azonano,

We live in fear of ‘superbugs’: infectious bacteria that don’t respond to treatment by antibiotics, and can turn a routine hospital stay into a nightmare. A 2015 Health Canada report estimates that superbugs have already cost Canadians $1 billion, and are a “serious and growing issue.” Each year two million people in the U.S. contract antibiotic-resistant infections, and at least 23,000 people die as a direct result.

But tests for antibiotic resistance can take up to three days to come back from the lab, hindering doctors’ ability to treat bacterial infections quickly. Now Ph.D. researcher Justin Besant and his team at the University of Toronto have designed a small and simple chip to test for antibiotic resistance in just one hour, giving doctors a shot at picking the most effective antibiotic to treat potentially deadly infections. Their work was published this week in the international journal Lab on a Chip.

A May 26, 2015 University of Toronto news release (also on EurekAlert), which originated the news item, provides more details about current testing regimes and about the new technique,

Resistant bacteria arise in part because of imprecise use of antibiotics—when a patient comes down with an infection, the doctor wants to treat it as quickly as possible. Samples of the infectious bacteria are sent to the lab for testing, but results can take two to three days. In the meantime, the doctor prescribes her patient a broad-spectrum antibiotic. Sometimes the one-size-fits-all antibiotic works and sometimes it doesn’t, and when the tests come back days later, the doctor can prescribe a specific antibiotic more likely to kill the bacteria.

“Guessing can lead to resistance to these broad-spectrum antibiotics, and in the case of serious infections, to much worse outcomes for the patient,” says Besant. “We wanted to determine whether bacteria are susceptible to a particular antibiotic, on a timescale of hours, not days.”

The problem with most current tests is the time it takes for bacteria to reproduce to detectable levels. Besant and his team, including his supervisor Professor Shana Kelley of the Institute for Biomaterials & Biomedical Engineering and the Faculties of Pharmacy and Medicine, and Professor Ted Sargent of The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, drew on their collective expertise in electrical and biomedical engineering to design a chip that concentrates bacteria in a miniscule space—just two nanolitres in volume—in order to increase the effective concentration of the starting sample.

They achieve this high concentration by ‘flowing’ the sample, containing the bacteria to be tested, through microfluidic wells patterned onto a glass chip. At the bottom of each well a filter, composed of a lattice of tiny microbeads, catches bacteria as the sample flows through. The bacteria accumulate in the nano-sized well, where they’re trapped with the antibiotic and a signal molecule called resazurin.

Living bacteria metabolize resazurin into a form called resorufin, changing its electrochemical signature. If the bacteria are effectively killed by the antibiotic, they stop metabolizing resazurin and the electrochemical signature in the sample stays the same. If they are antibiotic-resistant, they continue to metabolize resazurin into resorufin, altering its electrochemical signature. Electrodes built directly into the chip detect the change in current as resazurin changes to resorufin.

“This gives us two advantages,” says Besant. “One, we have a lot of bacteria in a very small space, so our effective starting concentration is much higher. And two, as the bacteria multiply and convert the resazurin molecule, it’s effectively stuck in this nanolitre droplet—it can’t diffuse away into the solution, so it can accumulate more rapidly to detectable levels.”

“Our approach is the first to combine this method of increasing sample concentration with a straightforward electrochemical readout,” says Professor Sargent. “We see this as an effective tool for faster diagnosis and treatment of commonplace bacterial infections.”

Rapid alternatives to existing antibiotic resistance tests rely on fluorescence detection, requiring expensive and bulky fluorescence microscopes to see the result.

“The electronics for our electrochemical readout can easily fit in a very small benchtop instrument, and this is something you could see in a doctor’s office, for example,” says Besant. “The next step would be to create a device that would allow you to test many different antibiotics at many different concentrations, but we’re not there yet.”

Here’s a link to and a citation for the paper,

Rapid electrochemical phenotypic profiling of antibiotic-resistant bacteria by Justin D. Besant, Edward H. Sargent, and Shana O. Kelley. Lab Chip, 2015, Advance Article DOI: 10.1039/C5LC00375J First published online 13 May 2015

This paper is behind a paywall.

It was surprising to see Ted (Edward) Sargent mentioned with regard to a lab-on-a-chip project. I have featured research from him and from his laboratory many times here and, as I recall, it’s always been focused on solar cells. This Dec. 9, 2014 post features the latest research solar cell research that I’ve stumbled across from Sargent and the University of Toronto.

Queen’s University (Canada) opens Kingston Nano-Fabrication Lab (KNFL)

First, there’s the opening (from an April 24, 2015 Queen’s University news release; Note: A link has been removed),

Queen’s University has secured its place at the forefront of transforming innovative research with the opening of the Kingston Nano-Fabrication Laboratory (KNFL).

The laboratory, located at Innovation Park, represents a milestone in the 30-year collaboration between Queen’s and CMC Microsystems for advancing Canadian strength in micro-nano innovation.

Some interesting details about the deal and the proposed uses for KNFL can be found in an April 24, 2015 story by Colleen Seto for Canada Foundation for Innovation (CFI),

… a brand-new, 3,000-square-foot, $5 million research facility [KNFL] located at the Queen’s University Innovation Park. The lab includes $2.5 million in new CFI-funded custom equipment for fabricating and prototyping new nano-scale inventions to get them to market quicker.

“We’re making devices, films, coatings, and materials, and examining their properties at the nanoscale,” says Ian McWalter, President and CEO of CMC Microsystems, which manages the operations of KNFL. “This fundamental materials research spills over into experiments of great use to industry, which then looks at how to commercialize he research results.”

The Queen’s University news release describes the longstanding relationship between the company managing the KNFL and the university,

“This facility is the latest manifestation of a long and productive relationship between Queen’s and CMC Microsystems,” says Ian McWalter, president and CEO of CMC. “For more than three decades, this partnership has enabled research and advanced training activities nationwide that would not have otherwise occurred. The KNFL is a significant enhancement, and we look forward to exploring the expanded opportunities that it offers us for building Canadian strength in micro-nano research and innovation.”

The CFI story provides more specifics about the potential workings of the facility,

Take, for example, the possibilities presented by KNFL’s laser micromachining system. “This new tool could be used to engrave channels into a piece of glass or polymer to produce a microfluidic device,” says Andrew Fung, Client Technology Advisor for Microsystems and Nanotechnology at CMC. Microfluidic devices take advantage of the behaviour of fluids at a very small scale to create things like “lab-on-a-chip” technologies that can be used to cheaply and quickly diagnose diseases in developing countries, among many other things. “Microfluidics grew out of silicon-based fabrication, which costs a lot of money,” explains Fung. “These other materials are lower cost, and can be single use, consumable, and disposable for a medical device.”

Much of KNFL’s new equipment was selected to enable rapid prototyping of new nanotechnologies. “Prototypes can be ready within hours or a day, instead of days or weeks. It shortens the whole innovation process so researchers can design, make, test, and get the information they need much faster,” says Fung.

The CFI story also contextualizes this project by noting that it’s part of a larger initiative,

The KNFL is also part of Embedded Systems Canada (emSYSCAN), a $50-million, five-year project aimed at shortening the microsystems development cycle. It involves more than 350 university researchers at 37 institutions across Canada’s National Design Network (NDN), which enables multidisciplinary research and collaboration through shared technologies and expertise.

The KNFL’s open-access model is aimed specifically at supporting the NDN. “The idea is to make [expertise and tools] more available to non-experts and to overcome barriers such as lab training to access this equipment,” says McWalter. “Through the service aspect of our lab, you wouldn’t necessarily twiddle the knobs yourself, but you would contract the lab to do things for you.” This provides vital learning opportunities for students while giving researchers a more efficient means to an end — accessing the equipment they need without having to invest the time and effort to learn how to use it.

Congratulations to the folks at Queen’s University!

What colour is your diagnosis?

Mark Lorch has written an April 16, 2015 piece for The Conversation (h/t the Guardian’s April 17, 2015 posting) about a very appealing approach to diagnostics (Note: A link has been removed),

If you’ve ever sat opposite a doctor and wondered what she was scribbling on her notepad, the answer may soon not only be medical notes on your condition, but real-time chemical preparations for an instant diagnostic test.

Thanks to the work of a team of researchers from California Polytechnic State University, recently published in the journal Lab on a Chip, chemicals formed into pencils can be made to react with one another by simply drawing with them on paper. The team may have taken inspiration from colouring books for their take on a chemical toolkit, but their approach could make carrying out simple but common diagnostic tests based on chemical reactions – for example diabetes, HIV, or tests for environmental pollutants – much easier.

Here’s a picture of the pens,

ReagentPencilsDiagnostics

Courtesy: Lab on a Chip

Lorch provides a good description of the technology giving descriptions of reagents and paper-based microfluidics, as well as, describing how the researchers turned the concept of colouring pencils into a diagnostic tool.

Lorch also provides a description of a specific test (Note: Links have been removed),

The team demonstrated a potential use of the reagent pencil technique by using it in place of a common test used by diabetics to check their blood glucose levels, which involves reacting a pinprick blood sample with a chemical solution and examining the result.

One pencil was constructed with a mixture of enzymes, one called horseradish peroxidase (HRP) and the other glucose oxidase (GOx). A second pencil contained a reagent called ABTS. When combined in the presence of glucose these react together to give a blue-coloured product. Comparing the results from their pencils on the pad with the more traditional dropper method used by diabetics the team found the results were identical.

This new ‘pencil kit’ diagnostic technology is easy to use and features a big improvement over the current diagnostic tests,

This is of course extremely easy to set up. Traditional diagnostic tests require training, while this pad and pencil system requires no more than skill than required to colour within the lines. The reagents are extremely stable once made into pencils – usually they would degrade in a matter of days as liquids, limiting how and where the tests can be made. However the reagent pencils showed no sign of degrading after two months.

Being able to use the pencils for two months as opposed to liquids that remain viable for a few days? That’s a huge jump and it makes me wonder about using these kits in harsh conditions such as desert climates and/or emergency situations. Materials that don’t need to be refrigerated and could be used for up to two months and don’t require intensive training could be very helpful. Lorch suggests some other possibilities as well,

… There’s scope to monitor environmental pollutants, carry out diagnostic tests in remote locations – not to mention teach chemistry in primary schools.

Here’s a link to and a citation for the study on the ‘colouring pencil kit’,

Reagent pencils: a new technique for solvent-free deposition of reagents onto paper-based microfluidic devices by Haydn T. Mitchell, Isabelle C. Noxon, Cory A. Chaplan, Samantha J. Carlton, Cheyenne H. Liu, Kirsten A. Ganaja, Nathaniel W. Martinez, Chad E. Immoos, Philip J. Costanzo, and Andres W. Martinez. Lab Chip, 2015, Advance Article DOI: 10.1039/C5LC00297D First published online 08 Apr 2015

This paper is open access but you do have to register on the site unless you have another means of access.

Optical nanoantennas open up lab-on-a-chip possibilities

A Feb. 24, 2015 news item on Nanowerk describes nanoantenna research coming out of Australia (Note: A link has been removed),

Newly developed tiny antennas, likened to spotlights on the nanoscale, offer the potential to measure food safety, identify pollutants in the air and even quickly diagnose and treat cancer, according to the Australian scientists who created them. The new antennas are cubic in shape. They do a better job than previous spherical ones at directing an ultra-narrow beam of light where it is needed, with little or no loss due to heating and scattering, they say.

In a paper published in the Journal of Applied Physics (“Optically resonant magneto-electric cubic nanoantennas for ultra-directional light scattering”), Debabrata Sikdar of Monash University in Victoria, Australia, and colleagues describe these and other envisioned applications for their nanocubes in “laboratories-on-a-chip.” …

A Feb. 24, 2015 American Institute of Physics news release on EurekAlert, which originated the news item, describes the work in detail,

… The cubes, composed of insulating, rather than conducting or semiconducting materials as were the spherical versions, are easier to fabricate as well as more effective, he [Sikdar] says.

Sikdar’s paper presents analysis and simulation of 200-nanometer dielectric (nonconductive) nanoncubes placed in the path of visible and near-infrared light sources. The nanocubes are arranged in a chain, and the space between them can be adjusted to fine-tune the light beam as needed for various applications. As the separation between cubes increases, the angular width of the beam narrows and directionality improves, the researchers say.

“Unidirectional nanoantennas induce directionality to any omnidirectional light emitters like microlasers, nanolasers or spasers, and even quantum dots,” Sikdar said in an interview. Spasers are similar to lasers, but employ minute oscillations of electrons rather than light. Quantum dots are tiny crystals that produce specific colors, based on their size, and are widely used in color televisions. “Analogous to nanoscale spotlights, the cubic antennas focus light with precise control over direction and beam width,” he said. [emphasis mine]

The new cubic nanoantennas have the potential to revolutionize the infant field of nano-electromechanical systems (NEMS). “These unidirectional nanoantennas are most suitable for integrated optics-based biosensors to detect proteins, DNA, antibodies, enzymes, etc., in truly portable lab-on-a-chip platforms of the future,” Sikdar said. “They can also potentially replace the lossy on-chip IC (integrated circuit) interconnects, via transmitting optical signals within and among ICs, to ensure ultrafast data processing while minimizing device heating,” he added. [emphasis mine]

Sikdar and his colleagues plan to begin constructing unidirectional cubic NEMS antennas in the near future at the Melbourne Center for Nanofabrication. “We would like to collaborate with other research groups across the world, making all these wonders possible,” he said.

I’m glad the writer included Sikdar’s explanation of spasers and quantum dots and thank them both for a new word, “lossy.” Here’s a link to and a citation for the paper,

Optically resonant magneto-electric cubic nanoantennas for ultra-directional light scattering by Debabrata Sikdar, Wenlong Cheng, and Malin Premaratne. J. Appl. Phys. 117, 083101 (2015); http://dx.doi.org/10.1063/1.4907536

This article is open access.

Two-organ tests (body-on-a-chip) show liver damage possible from nanoparticles

This is the first time I’ve seen testing of two organs for possible adverse effects from nanoparticles. In this case, the researchers were especially interested in the liver. From an Aug. 12, 2014 news item on Azonano,

Nanoparticles in food, sunscreen and other everyday products have many benefits. But Cornell [University] biomedical scientists are finding that at certain doses, the particles might cause human organ damage.

A recently published study in Lab on a Chip by the Royal Society of Chemistry and led by senior research associate Mandy Esch shows that nanoparticles injure liver cells when they are in microfluidic devices designed to mimic organs of the human body. The injury was worse when tested in two-organ systems, as opposed to single organs – potentially raising concerns for humans and animals.

Anne Ju’s Aug. 11, 2014 article for Cornell University’s Chronicle describes the motivation for this work and the research itself in more detail,

“We are looking at the effects of what are considered to be harmless nanoparticles in humans,” Esch said. “These particles are not necessarily lethal, but … are there other consequences? We’re looking at the non-lethal consequences.”

She used 50-nanometer carboxylated polystyrene nanoparticles, found in some animal food sources and considered model inert particles. Shuler’s lab specializes in “body-on-a-chip” microfluidics, which are engineered chips with carved compartments that contain cell cultures to represent the chemistry of individual organs.

In Esch’s experiment, she made a human intestinal compartment, a liver compartment and a compartment to represent surrounding tissues in the body. She then observed the effects of fluorescently labeled nanoparticles as they traveled through the system.

Esch found that both single nanoparticles as well as small clusters crossed the gastrointestinal barrier and reached liver cells, and the liver cells released an enzyme called aspartate transaminase, known to be released during cell death or damage.

It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential, Esch said. Long-term consequences for organs in proximity could be a concern, she said.

“The motivation behind this study was twofold: one, to show that multi-organ, in vitro systems give us more information when testing for the interaction of a substance with the human body, and two … to look at nanoparticles because they have a huge potential for medicine, yet adverse effects have not been studied in detail yet,” Esch said.

Mary Macleod’s July 3, 2014 article for Chemistry World features a diagram of the two-organ system and more technical details about the research,

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

HepG2/C3A cells were used to represent the liver, with the intestinal cell co-culture consisting of enterocytes (Caco-2) and mucin-producing (HT29-MTX) cells. Carboxylated polystyrene nanoparticles were fluorescently labelled so their movement between the chambers could be tracked. Levels of aspartate transaminase, a cytosolic enzyme released into the culture medium upon cell death, were measured to give an indication of liver damage.

The study saw that single nanoparticles and smaller nanoparticle aggregates were able to cross the GI barrier and reach the liver cells. The increased zeta potentials of these nanoparticles suggest that crossing the barrier may raise their toxic potential. However, larger nanoparticles, which interact with cell membranes and aggregate into clusters, were stopped much more effectively by the GI tract barrier.

The gastrointestinal tract is an important barrier preventing ingested substances crossing into systemic circulation. Initial results indicate that soluble mediators released upon low-level injury to liver cells may enhance the initial injury by damaging the cells which form the GI tract. These adverse effects were not seen in conventional single-organ tests.

Here’s a link to and a citation for the paper,

Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury by Mandy B. Esch, Gretchen J. Mahler, Tracy Stokol, and Michael L. Shuler. Lab Chip, 2014,14, 3081-3092 DOI: 10.1039/C4LC00371C First published online 27 Jun 2014

This paper is open access until Aug. 12, 2014.

While this research is deeply concerning, it should be noted the researchers are being very careful in their conclusions as per Ju’s article, “It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential … Long-term consequences for organs in proximity could be a concern … .”

A complete medical checkup in a stapler-sized laboratory

I find this device strangely attractive,

© 2014 EPFL

A March 4, 2014 news item on Azonano provides more information,

About the size of a stapler, this new handheld device developed at EFPL [École polytechnique fédérale de Lausanne] is able to test a large number of proteins in our body all at once-a subtle combination of optical science and engineering.

Could it be possible one day to do a complete checkup without a doctor’s visit? EPFL’s latest discovery is headed in that direction. Professor Hatice Altug and postoctoral fellow Arif Cetin, in collaboration with Prof. Aydogan Ozcan from UCLA [University of California at Los Angeles], have developed an “optical lab on a chip.” Compact and inexpensive, it could offer to quickly analyze up to 170,000 different molecules in a blood sample. This method could simultaneously identify insulin levels, cancer and Alzheimer markers, or even certain viruses. “We were looking to build an interface similar to a car’s dashboard, which is able to indicate gas and oil levels as well as let you know if your headlights are on or if your engine is working correctly,” explains Altug.

A March 3, 2014 EPFL news release, which originated the news item, describes the technique and the device in detail,

Nanoholes on the gold substrates are compartmented into arrays of different sections, where each section functions as an independent sensor. Sensors are coated with special biofilms that are specifically attracting targeted proteins. Consequently, multiple different proteins in the biosamples could be captured at different places on the platform and monitored simultaneously.

The diode then allows for detection of the trapped proteins almost immediately. The light shines on the platform, passes through the nano-openings and its properties are recorded onto the CMOS chip. Since light going through the nanoscaled holes changes its properties depending on the presence of biomolecules, it is possible to easily deduce the number of particles trapped on the sensors.

Laboratories normally observe the difference between the original wavelength and the resulting one, but this requires using bulky spectrometers. Hatice Altug’s ingenuity consists in choosing to ignore the light’s wavelength, or spectrum, and focus on changes in the light’s intensity instead. This method is possible by tuning into the “surface plasmonic resonance” – the collective oscillation of electrons when in contact with light. And this oscillation is very different depending on the presence or absence of a particular protein. Then, the CMOS chip only needs to record the intensity of the oscillation.

The size, price and efficiency of this new multi-analyze device make it a highly promising invention for a multiplicity of uses. “Recent studies have shown that certain illness like cancer or Alzheimer’s are better diagnosed and false positive results avoided when several parameters can be analyzed at once,” says Hatice Altug. “Moreover, it is possible to remove the substrate and then replace it with another one, allowing to be adapted for a wide range of biomedical and environmental research requiring monitoring of biomolecules, chemicals and bioparticles.” The research team foresees collaborating with local hospitals in the near future to find the best way to use this new technology.