Microanalysis of biological samples for early disease detection

A schematic drawing of solution measurement by using fabricated terahertz microfluidic chip. The chip consists of a local THz radiation point source, a single microchannel and a few arrays of split ring resonators. The THz waves are generated by irradiating laser beam from the backside of the crystal and efficiently interact with the solution flowing inside the microchannel. The optical microscope image of fabricated microfluidic chip is also shown.

Credit: Osaka University

https://www.sciencedaily.com/releases/2018/02/180219103211.htm

The use of terahertz (THz) waves for biosensing is currently receiving considerable attention. THz waves are able to detect molecular vibrations and rotations, without using labels that can affect the properties of the substances of interest.

However, until now, the diffraction limit of THz waves and their strong absorption by water have constrained this technique.

Microfluidic devices are also promising analytical systems because of the low sample volumes needed for sample measurement.

A group of researchers from Osaka University has now developed a nonlinear optical crystal (NLOC) chip, which combines THz waves with a microfluidic device, utilizing the close proximity of the THz wave source and the solution of interest in a microchannel. Their work was published in APL Photonics.

"Using our technique, we have been able to detect solution concentrations of several femtomoles in volumes of less than a nanoliter," corresponding author Masayoshi Tonouchi says. "Such high-sensitivity detection without the need for labelling moieties has great potential for future low-invasivity clinical techniques."

Early and rapid detection of a number of common diseases is expected to be one of the major applications of the technique. Cancer, diabetes, and the influenza virus could potentially be detected with only very small volumes of bodily fluid, reducing the pain and discomfort of numerous exploratory procedures for patients. In addition, the technique allows living cells to be analyzed in a non-destructive way, which has numerous potential benefits in research.

The developed NLOC chip is able to locally generate the THz radiation in close proximity to the single microchannel device, improving efficiency. The sensor chip was used to analyze mineral concentrations by comparing frequency shifts resulting from the presence of ions to those of pure water. Using this technique they determined a sensitivity of 31.8 femtomoles.

"Achieving high sensitivity without the need for a high-power optical or THz source, near-field probes or prisms, opens up a number of possibilities," lead author Kazunori Serita says. "We are very excited about the potential of our findings to lead to rapid detection and compact device design. In particular, we see our results accelerating the development of THz lab-on-a-chip devices."

This highly adaptable technology is likely to ripple out into many areas of analytical and biochemistry, as well as cell biology, and clinical medicine.

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Story Source:

Materials provided by Osaka University. Note: Content may be edited for style and length.

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Journal Reference:

1. Kazunori Serita, Eiki Matsuda, Kosuke Okada, Hironaru Murakami, Iwao Kawayama, Masayoshi Tonouchi. Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms. APL Photonics, 2018; 3 (5): 051603 DOI: 10.1063/1.5007681

Breathtaking: Wright State researchers developing disease-detecting exhalation device

Assistant physics professor Ivan Medvedev (foreground) with student researchers (left to right) Jessica R. Thomas, Tianle Guo and Daniela Branco.

http://webapp2.wright.edu/web1/newsroom/2013/10/02/breathtaking-wright-state-researchers-developing-disease-detecting-exhalation-device/

By Jim Hannah

 

Diabetes, kidney disease, even cancer. Their presence in the human body can change the smell and chemistry of a person’s breath. So a Wright State University researcher and his team are building a novel breath-analysis device designed to detect these and other diseases.
“It will be a Breathalyzer on steroids,” said Ivan Medvedev, Ph.D., an assistant physics professor who is heading the effort. “This will allow us to have a warning of sorts. We are very excited about it. The technology is solid.”
Medvedev and his team of student researchers—Jessica R. Thomas, Tianle Guo and Daniela Branco—are working their magic in a basement lab at Fawcett Hall forested with equipment.
Long, insulated gas-filled cylinders run across a laboratory table top. Open laptop computers shadowed by spaghetti-like strands of red, yellow and black computer connecting wires stand at attention like sentinels. A towering white tank of liquid nitrogen muscles into the space.
Medvedev’s plan is to use terahertz radiation to detect chemical changes in the human breath. Terahertz radiation consists of invisible light waves in the electromagnetic spectrum higher in frequency than microwave and lower than infrared light. It has been used for years by astronomers to detect molecules in interstellar space in an effort to determine how stars form.
Terahertz radiation has an advantage over other electromagnetic waves because it is so sensitive and produces very sharp spectra, making it easier to identify a wide variety of chemical molecules. Engineers have just recently developed somewhat simple terahertz radiation generators and detectors. In addition, computers have become powerful enough to handle all of the data created in the process.
“Technology is at the point where we can actually now detect those spectra and use them not for interstellar detection but for terrestrial applications,” Medvedev said.
Up until now, the standard technology for chemical analysis has been gas chromatography-mass spectroscopy, which fragments molecules with an electron beam. However, that technology has a limited number of detection channels and trouble analyzing complex mixtures.
“That’s where we come in,” said Medvedev. “We detect spectra and there are so many lines; the signatures are very unique. That is one of the biggest advantages.”
The goal is to come up with a non-invasive way of making an early diagnosis of a disease and minimizing its impact. The detector will be designed to identify and quantify chemicals in the breath such as the acetone, toluene and methanol associated with diabetes or the ammonia and urea linked to kidney disease or the sulfur-bearing compounds associated with liver cancer and cirrhosis.
One of the ambitious goals of the research is to tackle the detection of cancer, which is not likely to manifest itself with a single chemical in human breath.
“This technology will enable us to actually detect hundreds of chemicals simultaneously from a single exhalation,” Medvedev said. “The sensor will detect a variety of chemicals with very high accuracy of what’s in your breath. And then having established the baselines of those chemicals, you can actually draw conclusions about what disease that patient may have. We’re moving into something that nobody has done before.”
Medvedev and team are currently trying to determine what levels of the chemicals are normal in the human breath so they can detect elevated levels. Then the equipment must be miniaturized and made less expensive so it can be used commercially. Finally, it must undergo clinical testing on patients and others to see if it works. The whole process could take anywhere between five and 15 years.
Medvedev and his team have won a $100,000 share of a grant from Samsung for the research, with an opportunity to extend it for up to three years. The electronics giant is hoping to develop a compact, handheld device that will detect chemicals linked to diabetes. Wright State is collaborating with the University of Texas at Dallas, which has the technology to miniaturize the detectors and strong ties to the local medical community.
The technology may also be helpful in sniffing out pollution and detecting chemical attacks by terrorists.
“The military is also interested in this technology,” said Medvedev. “They would like to have an early warning of soldiers coming down with something before getting deployed. If you have a flu that has not yet expressed symptoms, you do not want to send a sick soldier to the battlefield.”
Medvedev’s paper on breath analysis was just accepted by Applied Physics Letters, a weekly peer-reviewed scientific journal published by the American Institute of Physics. The journal emphasizes new developments that lay the groundwork for fields that are rapidly evolving.
Medvedev grew up in Moscow, obtaining his master’s degree at the Moscow Institute of Physics and Technology. He earned his Ph.D. at The Ohio State University and stayed there for five years as a research scientist before landing a faculty position at Wright State three years ago.
“What we have here is a fairly extensive research cluster of terahertz scientists,” Medvedev said. “All of the infrastructure is here. It’s a very good environment for terahertz research.”