Abstract-Label-Free Observation of Micrometric Inhomogeneity of Human Breast Cancer Cell Density Using Terahertz Near-Field Microscopy

 

Kosuke Okada, Quentin Cassar, Hironaru Murakami, Gaëtan MacGrogan , Jean-Paul Guillet, Patrick Mounaix, Masayoshi Tonouchi, Kazunori Serita

https://www.mdpi.com/2304-6732/8/5/151

Terahertz-light imaging is attracting great attention as a new approach in non-invasive/non-staining biopsy of cancerous tissues. Positively, terahertz light has been shown to be sensitive to the cell density, the hydration content, and the chemical composition of biological samples. However, the spatial resolution of terahertz imaging is typically limited to several millimeters, making it difficult to apply the technology to image biological tissues which have sub-terahertz-wavelength-scale inhomogeneity. For overcoming the resolution, we have recently developed a terahertz near-field microscope with a spatial resolution of 10 µm, named scanning point terahertz source (SPoTS) microscope. In contrast to conventional far-field terahertz techniques, this microscope features the near-field interactions between samples and point terahertz sources on a sub-terahertz-wavelength scale. Herein, to evaluate the usefulness of terahertz imaging in cancer tissue biopsy in greater detail, we performed terahertz near-field imaging of a paraffin-embedded human-breast-cancer section having sub-terahertz-wavelength-scale inhomogeneity of the cancer cell density using the SPoTS microscope. The observed terahertz images successfully visualized local (~250 µm) inhomogeneities of the cell density in breast invasive ductal carcinoma. These results may bypass the terahertz limitation in terms of spatial resolution and may further motivate the application of terahertz light to cancer tissue biopsy.

Abstract-Terahertz Excitonics in Carbon Nanotubes: Exciton Autoionization and Multiplication

Filchito Bagsican, Michael Wais, Natsumi Komatsu, Weilu Gao, Weilu Gao, Lincoln W. Weber, Kazunori Serita,  Hironaru Murakami, Karsten. Held, Frank A. Hegmann, Masayoshi Tonouchi, Junichiro Kono, Iwao Kawaya, Marco Battiato

https://pubs.acs.org/doi/10.1021/acs.nanolett.9b05082

Excitons play major roles in optical processes in modern semiconductors, such as single-wall carbon nanotubes (CNTs), transition metal dichalcogenides, and 2D perovskite quantum wells. They possess extremely large binding energies (>100 meV), dominating absorption and emission spectra even at high temperatures. The large binding energies imply that they are stable, that is, hard to ionize, rendering them seemingly unsuited for optoelectronic devices that require mobile charge carriers, especially terahertz emitters and solar cells. Here, we have conducted terahertz emission and photocurrent studies on films of aligned single-chirality semiconducting CNTs and find that excitons autoionize, i.e., spontaneously dissociate into electrons and holes. This process naturally occurs ultrafast (<1 ps) while conserving energy and momentum. The created carriers can then be accelerated to emit a burst of terahertz radiation when a dc bias is applied, with promising efficiency in comparison to standard GaAs-based emitters. Furthermore, at high bias, the accelerated carriers acquire high enough kinetic energy to create secondary excitons through impact exciton generation, again in a fully energy and momentum conserving fashion. This exciton multiplication process leads to a nonlinear photocurrent increase as a function of bias. Our theoretical simulations based on nonequilibrium Boltzmann transport equations, taking into account all possible scattering pathways and a realistic band structure, reproduce all of our experimental data semiquantitatively. These results not only elucidate the momentum-dependent ultrafast dynamics of excitons and carriers in CNTs but also suggest promising routes toward terahertz excitonics despite the orders-of-magnitude mismatch between the exciton binding energies and the terahertz photon energies.

Abstract-A Terahertz-Microfluidic Chip with a Few Arrays of Asymmetric Meta-Atoms for the Ultra-Trace Sensing of Solutions

Kazunori Serita,  Hironaru Murakami, Iwao Kawayama, Masayoshi Tonouchi

https://www.mdpi.com/2304-6732/6/1/12/htm

Biosensing with terahertz (THz) waves has received large amounts of attention due to its potential to detect the functional expression of biomolecules in a label-free fashion. However, many practical challenges against the diffraction limit of THz waves and the strong absorption of THz waves into polar solvents still remain in the development of compact biosensors. Here, we present a non-linear, optical, crystal-based THz-microfluidic chip with a few arrays of asymmetric meta-atoms, an elementary unit of metamaterials, for the measurement of trace amounts of solution samples. A near-field THz emission source, that is locally generated in the process of optical rectification at a fs (femtosecond) laser irradiation spot, induces a sharp Fano resonance and modifies the resonance frequency of the meta-atoms when the channel is filled with solution samples of different concentrations. Using this chip, we successfully detected minute changes in the concentration of trace amounts of mineral water and aqueous sugar solutions by monitoring the shift in the resonance frequency. A higher detectable sensitivity of 1.4 fmol of solute in a 128 pL volume of solution was achieved. This was an improvement of one order of magnitude in the sensitivity compared to our previous experiment.

Abstract-Reflection type scanning laser terahertz near-field spectroscopy and imaging system for bio-applications

Kosuke Okada, Kazunori Serita, Iwao Kawayama, Hironaru Murakami, and Masayoshi Tonouchi

https://www.osapublishing.org/abstract.cfm?URI=cleo_si-2018-SW3D.4

We developed a reflection type scanning laser THz near-field spectroscopy and imaging system and evaluated its basic performance. We found that this system has huge potential for high-resolution, high-sensitive and high-speed biological measurements.

© 2018 The Author(s)

Sensing Method Could Detect Cancer & Diabetes Earlier

https://www.azosensors.com/news.aspx?newsID=12364

By Louise SaulFeb 27 2018

Scientists at Osaka University have developed a new sensing method, which has the potential to detect both cancer and diabetes earlier than ever possible before.

The use of terahertz (THz) waves for biosensing is currently of great interest to scientists and is receiving considerable attention. The team in Osaka have developed a THz microfluidic chip with arrays of meta-atoms that can be used for microanalysis. It is highly sensitive, and label-free, for measurements of biological samples. The new chip can detect trace amounts of known materials and minimal changes in optical constants. The research was published in APL Photonics.

THz radiation lies in between infrared and microwave radiation. The terahertz region provides essential information that clarifies biological reaction dynamics, including the hydrogen bonds and hydrophobic interactions, and it is at comparatively lower energy than that of infrared absorption. They can detect molecular vibrations and rotations, without using labels that can affect the properties of the substances of interest.

Microfluidic devices only need a very low sample volume for measurements, so they are seen as very promising analytical systems. The group from Osaka University have now developed a nonlinear optical crystal (NLOC) chip, combining the THz waves with a microfluidic device, meaning that the proximity of the THz wave source and the solution of interest in a microchannel can be combined.

The early and rapid detection of common diseases is set to be a major application of the technique. There is the potential that cancer, diabetes, and even the influenza virus would be able to be detected with very small volumes of bodily fluid. The sample volume needed allows for the patients to have their pain and discomfort from exploratory procedures reduced. The new technique also has another major benefit of allowing living cells to be analyzed in a non-destructive way.

The technique has been limited previously due to the diffraction limit of THz waves and their strong absorption by water. The new research has shown that THz time-domain spectroscopy (THz-TDS) is a technique that can give new insights into the functional expression and structural change of water, biopolymers, and DNA. When THz methods can be combined with microfluidic devices, it allows for the development of compact THz sensors, as well as new analytical THz devices that have a higher sensitivity.

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

Professor Masayoshi Tonouchi, Professor of the Tonouchi lab at Osaka University

The sensor chip compared frequency shifts resulting from the presence of ions to those of pure water to analyze mineral concentrations. The chip was tested by using both distilled water and commercial mineral water, and when observing the amount of shift from the resonance frequency of pure water, they found that the solute can be detected with a sensitivity of up to 31.8 femtomoles. The sensitivity of the technique is comparable to standard fluorescence systems, but it can be improved by further optimization of the structure and the arrangement of meta-atoms. Altering the channel depth to reduce the THz absorption into the water can also optimize results.

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.

Kazunori Serita, Co-Author

Serita explains how their potential findings could lead to rapid detection and compact device designs. He believes the results will lead to an acceleration in the development of THz lab-on-a-chip devices. The new adaptable technology has the potential to have a wide range of uses across many areas, including biochemistry, analytical chemistry, cell biology, and clinical medicine. The low cost of NLOC chips would also allow for disposable and compact sensors, which would be highly beneficial to both fields of medicine and biology.

Thumbnail Image Credit: GiroScience/Shutterstock

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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

Abstract-Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

Kazunori Serita, Eiki Matsuda, Kosuke Okada, Hironaru Murakami, Iwao Kawayama, Masayoshi Tonouchi,

http://aip.scitation.org/doi/abs/10.1063/1.5007681

We present a nonlinear optical crystal (NLOC)-based terahertz (THz) microfluidic chip with a few arrays of split ring resonators (SRRs) for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

Abstract-Perfect Broadband Terahertz Antireflection by Deep-Subwavelength, Thin, Lamellar Metallic Gratings

 

Lu Ding Qing Yang Steve Wu Jun Feng Song^,Kazunori Serita Masayoshi Tonouchi, Jing Hua Teng
http://onlinelibrary.wiley.com/doi/10.1002/adom.201300321/abstract
Perfect broadband terahertz antireflection coatings are demonstrated by deep-subwavelength, thin, lamellar metallic gratings both in theory and experiment. Abrupt phase changes introduced by grating to terahertz wave traversing the coated surface can be tuned from 0 to π as a function of grating parameters. At π/2, the impedance difference between two dielectrics is matched and perfect antireflection occurs.