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SRESEARCHKorea Research Institute of
Standards and Science
kgINSTITUTEKorea Research Institute of
Standards and Science
mSTANDARDSKorea Research Institute of
Standards and Science ASCIENCEKorea Research Institute of
Standards and Science
K KOREAKorea Research Institute of
Standards and Science
mol
cd
Issue 02, 2018
KRISSNewsletter
http://www.kriss.re.kr/eng
Research HighlightsDiscrimination of single nucleotide mismatches enables early cancer diagnosis
Underwater stealth technology becomes possible
KRISS commercializes an interferometric sensor to detect defective glasses
Development of trimer atom based gas field ion source for ion microscopy
Towards realization of invariant resistance standard at mega-ohm level
News and EventsKRISS attends the 16th NMIJ-KRISS SUMMIT in Japan
President of INMETRO visits KRISS
KRISS holds the International Symposium of Standard Reference Data (ISSRD) 2018
KRISS holds the Emerging Scientist Workshop 2018
Issue 02, 2018 _ 2
Research HighlightsKRISS Newsletter
Research Highlights
Discrimination of single nucleotide mismatches enables earlycancer diagnosis- Low-cost, high-sensitivity miRNA sensor developed -
RNA molecules in the human body express protein
according to genetic information in DNA. A microRNA
(miRNA) is a small RNA molecule that suppresses protein
expression of other RNA, thereby playing a key role in all
stages from cell birth to death.
A research team of KRISS developed a low-cost, high-
sensitivity sensor capable of accurately detecting miRNA
in human tissues.
Led by principal research scientist Tae Geol Lee of the
Center for Nano-Bio Measurement, the team succeeded in
developing an LSPR*-based highly-sensitive miRNA
sensor through simple enzyme reactions. The sensor allows
quantitative analysis, distinguishing between sequences
with single nucleotide differences, and is expected to have
diverse applications in cancer diagnostics and evaluation of
anti-cancer drugs.
miRNAs are RNA molecules with short sequences (about
22 nucleotides), and there are many kinds of miRNAs in
human cells and they are known to play various roles.
miRNAs do not contain genetic information but bind with
RNAs to suppress protein expression. They are closely
related to various biological phenomena since they affect
protein expression.
Recently, the academia has been focusing on early
diagnosis of diseases based on the unique miRNA
properties. For instance, cancer patients have an excessive
number of miRNAs, which bind to tumor suppressing
genes in the body. These miRNAs inhibit the production of
proteins that interfere with the growth of cancerous cells.
The detection of specific miRNAs can be used as an
indicator for early diagnosis of diseases.
Quantitative analysis and accuracy with high sequence
specificity are essential for miRNA sensor as miRNAs
assume completely different functions with a single
nucleotide substitution. Currently, PCR is a widely used
method to analyze miRNAs. However, PCR requires gene
amplification and additional labeling, and such
modifications lead to less accurate results.
By utilizing LSPR technology, Lee and his team succeeded
in developing a highly-sensitive miRNA sensor that does
not require labeling or gene amplification. Thanks to its
high sequence specificity, the device can distinguish
between sequences with only a single nucleotide
substitution.
To overcome the weak wavelength shift, which is an issue
with current LSPR technology, the team induced selective
enzyme reactions on the gold nanostructure surface of the
sensor. Reproducible signal changes with high sensitivity
were obtained by generating wavelength changes larger
than the current standard by several dozen times.
* Localized Surface Plasmon Resonance (LSPR): An opticalphenomenon resulting from the interactions between aplasmonic nanoparticle or nanostructure and light of aspecific wavelength.
Lee(back) and his team developing the highly-sensitivemiRNA sensor
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 3
SEM images of the nanostructure surface before (left) and after (right) enzyme reactions
Wavelength shift is not significant before enzyme reactions(left), but becomes more pronounced after enzymereactions(right), allowing easier miRNA detection
Lee said, “The sensitive and sequence-specific miRNA
sensor developed by KRISS can be applied to various
analytical platforms in the medical industry as it is highly
efficient and reproducible. The sensor can be produced at
half the cost and on a larger scale, thus showing promise in
commercialization.”
Supported by the Biomedical Technology Development
Project of the Ministry of Science and ICT, the study was
published in Biosensors and Bioelectronics on May 1.
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 4
Underwater Objects, which cannot be reached by
electromagnetic waves or radar, are detected based on
reflected acoustic waves. Acoustic waves are reflected off
the surface of an object. However, there is a new material
that allows acoustic waves to pass through, remaining safe
and undetected.
A research team composed of Wonjae Choi, a principal
research scientist at the Center for Safety Measurement of
KRISS and Semyung Wang, a professor in the Department
of Mechanical Engineering of Gwangju Institute of Science
and Technology (GIST, President Seung Hyeon Moon),
developed a double-zero-index metamaterial and
successfully conducted experiments in a water tank.
Recently, metamaterials have come under the spotlight as
they exhibit properties that cannot be obtained by natural
materials. A good example is metamaterial cloaking.
Invisibility cloaks control light refracted in the positive
direction, and can even achieve negative or zero refractive
index.
The above can also be applied to acoustic waves. Similar to
how invisibility is achieved by controlling the refraction of
light, underwater stealth capabilities can be attained
through acoustic waves having zero refractive index.
However, underwater acoustic waves with double-zero
refractive index have only been realized in computer
simulations. This is because of the hypothesis that
refractive index can only be controlled when the matrix is
the slowest material.
The team, composed of members of KRISS and GIST,
presented results that overturn the slow material hypothesis.
Double-zero-index phononic crystals* were obtained
through arrays of copper, which is three times faster than
water with regard to transmission rate. The proposed "fast
material hypothesis" is not in complete opposition to the
existing hypothesis, and can be explained through the
symmetry of the lattice structure. The results are expected
to serve as a theoretical basis for future studies on zero
refractive index.
When an acoustic wave passes through a zero-index
metamaterial, the phase at the end is the same as the phase
before entering. This is why the wave appears to be
continuous and undistorted. Moreover, the wave can
converge or diverge depending on the end shape of the
metamaterial.
Choi said, "By using metamaterials for the surface of
submarines, we can create stealth submarines that cannot
be detected using acoustic wave sensors." Professor Wang
of GIST said, "Since sound can be controlled in the desired
directions, the process can be applied to not only
mechanical and medical industries, but also to solve noise
pollution caused by construction sites."
Supported by the Creative Fusion Research Project of the
National Research Council of Science and Technology, the
study was published in the leading journal Scientific
Reports (IF: 4.259) in May.
* Phononic crystal: A periodic arrangement of a unit celldesigned for the purpose of acoustic control
Underwater stealth technology becomes possible- Double-zero-index metamaterial passes acoustic waves without reflection -
Choi (bottom) and his team conducting the double-zero-index metamaterial experiment in a water tank
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 5
Research applications
1. Logistics: Stealth submarines
·Acoustic waves are used to detect the location of fish or
submarines underwater. Stealth submarines, which
allow acoustic waves to pass through instead of being
reflected, can be designed using zero-index
metamaterials.
2. Acoustics: Design of optimal sound source
·Standard sound sources, in the form of square or plane
waves, are required to test acoustic systems and sensors.
Ideal sound sources can be produced using zero-index
metamaterials and utilized as standard sound sources.
3. Construction/machinery: Noise and vibration control
·The level of noise in buildings or machines should be
minimal. Using zero-index metamaterials, noise and
vibration can be diverted to other directions. Energy
harvesting can be employed to capture energy while
reducing vibration at the same time.
Double-zero-index metamaterial experimental setup andresults.
- (a) Experimental setup (b) Simulation and experimentalresults with and without the metamaterial
: Plane waves having the same phase generated withmetamaterial
Schematic of phase of plane waves-ex) When the phase of a wave entering a metamaterial is 1,
the phase when existing the end of the zero-indexmetamaterial is also 1.
(Wave shows no changes if there is no metamaterial)
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 6
Flat-panel displays sold in the Republic of Korea have
grown by an average of 10 inches over the past seven years.
As manufacturing process becomes more complicated
along with unexpected variables, it is quite difficult to
maintain low level of a defect rate of large glass panels. For
this reason, strict inspection is required during the whole
manufacturing processes.
KRISS developed a robust technology detecting defects of
large glass panels, and then has commercialized a thickness
measuring sensor successfully by transferring the
technology to a company specializing in optical inspection.
A team led by Jonghan Jin, principal research scientist of
the Center for Optical Metrology at KRISS, developed a
sensor capable of measuring physical thickness and
refractive index of large glass substrates in real-time, even
under the strong vibration conditions.
As customers prefer ultra-large screens of their flat-panel
displays, the demand on large bare glasses has been
increasing, which leads the expansion of the related market.
Owing to size of the large bare glasses over several meters,
the production of the glasses having uniform thickness is
not an easy work. Irregular form of the glasses caused by
thickness variation may damage image pixels and distort
images.
Under harsh environmental conditions with strong
vibration, however, conventional inspection machines have
been rarely worked in production lines.
The team led by Jin developed a sensor capable of
measuring physical thickness and refractive index of large
glass substrates in real-time, which works based on optical
interferometry. With the adoption of transmissive
configuration, the sensor achieves the world's best technical
performance in terms of vibration insensitivity without
degradation of measurement accuracy.
Another novelty of this developed technology is to measure
the refractive index of bare glasses. Since optical
interferometers provides only optical thickness, the
conventional interferometric techniques need to know the
refractive index in advance to extract the physical thickness
from the optical thickness. On the other hands, the newly
developed sensor can measure physical thickness and
refractive index at the same time.
Jin said, “The measurement technology is optimized to
apply for the manufacturing process of glass substrates
being used in a wide range of IoT-based products. We have
realized simultaneous measurements of physical thickness
and refractive index under strong vibration conditions,
which is not possible with other conventional sensors.”
In 2017, KRISS transferred the technology to Novitec
specializing in optical inspection. Novitec has succeeded in
commercialization, and signed a product supply agreement
with a global glass manufacturer in July 2018.
Junyoung Lee, the CEO of Novitec, said, “We have
developed an outstanding product thanks to technology
developed by KRISS, and supplied it to a global company.
We are planing to expand our business territories and go
into global markets, not only for glass substrates, but also
solar panels and silicon wafers.”
KRISS commercializes an interferometric sensor to detectdefective glasses- Development of a sensor for measuring thickness and refractive index of large glass panels -
Jin (far right) and his team measuring the physicalthickness and refractive index of a large glass panel
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 7
In the world of microscopy, quality depends on beams such
as light, electrons, and ions. How such sources are utilized
determine the performance of microscopes. Higher-
resolution images can be obtained when beams are
concentrated to a small area and then emitted.
KRISS developed novel ion beam* technology for helium
ion microscopes, which are recognized as next-generation
microscopy.
The research team led by In-Yong Park of the Photon and
Electron Instruments Team at KRISS designed an ion
source device*, and succeeded in generating ion beams
with a trimer atom probe.
Helium ion microscopy not only offers sub-nanometer
resolution, but is also suited for precision manufacturing of
dimensions less than 10 nanometers. For this reason,
helium ion microscopes have diverse applications in
various fields including nanoprocess technology, materials
science, and biology.
Ion sources must be precisely designed to achieve high
resolution in helium ion microscopy. The area over which
ion beams are emitted is made smaller by sharpening the
probe tip. The key to a sharp probe tip is to leave a minimal
number of atoms at the tip.
High-performance ion beam technology is very important
in ion microscopy, but commercial microscopes with trimer
atom probes are made by only a handful of international
companies due to their technical complexity.
A major element that interferes with probe tip fabrication is
the oxide film. When the probe is exposed to air before
Development of trimer atom based gas field ion source for ionmicroscopy- Advances in ion beam technology with reverse use of oxide film -
Park (back) and his team performing the trimer atom etching test
* Ion beam: A charged particle beam comprised of ion. An ionmicroscope uses an ion beam as its source.
* Ion source device: A device that generates ion beams by ionizing inactivegases surrounding the probe when a strong positive voltage isapplied after introducing inactive gases such as helium, neon,and xenon
A sensor capable of measuring physical thickness and refractive index of large glass substrates at real-time, which is commercialized based on measurement technology developed by KRISS
entering the vacuum environment, an oxide film forms on
the tungsten surface. In the past, this oxide film was
removed through heat treatment of the probe.
Park and his team succeeded in developing a trimer atom
probe by making use of the oxide film, which was
previously removed by applying heat to the insulating
layer. The team used the oxygen in the insulating layer for
etching, allowing the probe to have a sharper tip.
The significance of this study is that it lays a foundation to
develop more advanced microscopes without relying on
exports. Since heat treatment is no longer necessary, ion
beams can be generated more conveniently and efficiently.
Park said, “The ion beam technology reduces the number of
steps involved compared to existing equipment. It is
expected to significantly enhance the competitiveness of the
local market, which is dominated by imports. Our ultimate
goal is to develop a single atom probe that uses only a single
atom to achieve three times greater brightness.”
Supported by the Nanotechnology Development Project of
the National Research Foundation of Korea, the study was
published online in the June issue of the leading journal,
Ultramicroscopy.
Research HighlightsKRISS Newsletter
Issue 02, 2018 _ 8
Comparison of multi-atom ion source (left) and trimer atom ion source device (right)
- The multi-atom probe before etching (left) emits ion beamsin various directions over a large area,
while the proposed probe (right) emits high-brightness ionbeams over a very small area (three atoms).
Fabrication of the trimer atom probe using the ion sourcedevice
- Etching of the probe to the size of three atoms using oxygenin the insulating layer
Towards realization of invariant resistance standard at mega-ohmlevel- National competitiveness in metrology demonstrated through Korea-Japan collaboration -
KRISS has played a pivotal role in the realization of
invariant high resistance, which may serve as a standard at
MΩ-level.
A team led by principal research scientist, Dong-Hun Chae
of the Center for Electromagnetic Metrology at KRISS has
contributed significantly through precision measurements
of quantum Hall resistance array to the realization of 1 MΩΩ*
quantum resistance. The study, conducted jointly with
Japanese researchers at the National Metrology Institute of
Japan (NMIJ), verified for the first time that high resistance
values derived from a quantum Hall resistance array remain
unchanged over time.
Resistance, the basic element of any electronic circuit, is
required for the operation of electronic devices. Resistance
* 1 M : 1,000,000 ohm (Ω). Ohm (Ω) is the unit of electricalresistance.
standards ensure that resistance values are accurate and
reliable. Many industries have adopted resistance standards
because deviation from required resistance affects both
current and voltage, leading to fatal functional problems in
products.
The standard of resistance is based on the Quantum Hall
effect* discovered by German scientist, Klaus von Klitzing
in 1980.
Advances in science and technology, however, presented
another challenge. Despite the increased demand for MΩ-
level resistance, the quantum Hall resistance at 12.9 KΩwas inadequate as a standard for high resistance. For this
reason, artifactual metal resistors are used for high
resistance standards.
To realize an invariant high resistance, NMIJ fabricated a 1
MΩquantum Hall resistance array by connecting about 90
resistors in series and parallel. They faced challenges in the
precise validation of the 1 MΩ array resistance due to the
100 times smaller applied current for precision
measurements compared with the quantum Hall resistance
standard. NMIJ requested KRISS, which is capable of the
resistance metrology in the top flight, to participate in a
joint study to overcome this issue.
Chae and his team succeeded in experimental
demonstration that the array resistance is invariant with
time within the relative measurement uncertainty of 10-8
using a Cryogenic Current Comparator. Similar to the act
of placing two loads on a weighing scale, the team directly
compared the proposed quantized Hall array resistance with
the quantum Hall resistance standard.
The MΩ-level invariant quantum-mechanical resistance
opens up new possibilities in science and across industries.
This is because a quantum mechanical high resistance is
needed for the precision measurement of a small current
source and its stable generation. It is expected to drive
technological innovation in precision measurements over
various areas including, for instance, the determination of
density of particulate matter and the radiometry in cancer
treatment.
Chae said, “Quantum Hall array resistance can be utilized in
various industries and research areas directly related to the
lives of citizens. It can be also applied to the precision
evaluation of single electron current sources, which may play
an important role in a realization of the new SI ampere (A).”
The study was published in the October issue of
Metrologia, the leading international journal on metrology
published by the International Bureau of Weights and
Measures in Paris.
Research HighlightsKRISS Newsletter
* Quantum Hall effect :A phenomenon in which the Hall resistance is quantizedwith respect to the magnetic field arising from the quantummechanical wave nature of electron. This effect is distinctlydifferent from the linear magnetic field dependance of theclassical Hall resistance stemming from the Lorentz force.Quantized Hall resistance is used as the resistance standardbecause it is reproducible and can be calculated with onlythe electron charge and the Planck constant.
Professor Klaus von Klitzing mentioning the precisionmeasurement data acquired at KRISS in the Conference
on Precision Electromagnetic Measurements (CPEM)held in Paris, France last July
Chae preparing the precision measurements of thequantized Hall array resistance
Issue 02, 2018 _ 9
News and EventsKRISS Newsletter
News and Events
Issue 02, 2018 _ 10
KRISS attends the 16th NMIJ-KRISS SUMMIT in JapanKRISS attended the 16th NMIJ-KRISS Summit on July 10 in Sapporo, Hokkaido, Japan. Seven delegates from KRISS
including Dr. Sang-Ryoul Park, President of KRISS, participated in this summit.
KRISS and NMIJ shared current status, R&D activities, and strategic plans of each institute. KRISS presented the research
highlights in the field of advanced instrumentation and quantum technology. Also they discussed cooperation package
regarding common research interest and the way of promoting the redefinition of the SI unit.
KRISS and NMIJ have had annual summit since 2003 in order to share the views on global metrology issues and discuss the
future strategy for bringing advancement as well as harmony in metrology community in globe.
President of INMETRO visits KRISSProf. Carlos Augusto de Azevedo, the President of INMETRO (Instituto Nacional de Metrología, Qualidade e Tecnologia) and
its director of International Cooperation visited KRISS on August 31.
KRISS and INMETRO have collaborated on the exchange of technical information, nanometrology, and other fields of mutual
interest since the MoU between KRISS and INMETRO in 2011, and for further cooperation they discussed the renewal of this
MoU in this meeting. Also, they discussed how to actively enhance the research cooperation between institutes and then visited
three laboratories in KRISS, which are the center for optical metrology, electromagnetic metrology and Watt Balance team.
Based on the visit in August, KRISS and INMETRO signed the MoU on November 14 during the 26th CGPM and agreed to
widen the cooperation including the areas of life science.
News and EventsKRISS Newsletter
Issue 02, 2018 _ 11
KRISS holds the International Symposium of Standard Reference Data (ISSRD) 2018KRISS held the International Symposium of Standard Reference Data (ISSRD) 2018 from September 11 to 12 in Seoul, Korea.
At this year's ISSRD, under the main theme "For the Value of Reliable Data", over 100 experts in standard reference and data
science were invited to discuss the value expansion through improvement of data reliability and the role of reference standard
and measurement standard.
Especially in the plenary session on first day, Dr. Anne. L. Plant and Dr. Rober Hanisch from NIST delivered invited talks on
data science. Also, there was a round-table conference on data standard with NIST, NCSRD(National Center for Standard
Reference Data), KISTI(Korea Institute of Science and Technology Information), NIA(National Information society Agency)
and KDATA(Korea DATA Agency) in order to share further related issues and policies.
KRISS holds the Emerging Scientist Workshop 2018KRISS hosted the 4th Emerging Scientist Workshop (ESW) from September 12 to 14 at KRISS, Daejeon, Korea. ESW, which
started in 2015, is an annual international event that aims for sharing knowledge and experiences and deepening the cooperation
between young researchers of NMIs in APMP region. This year, about 40 young researchers from KRISS(Korea), NIM(China),
and NMIJ(Japan) participated in this workshop.
On its first day, KRISS invited Dr. Anne Plant and Dr. Robert Hanisch from NIST(USA) and they delivered invited talks on the issue
of the importance of data reliability and the data science which was very informative for young metrologist. In addition, there were
flash presentation and poster session which lead ESW participants to actively introduce and discuss their up-to-date research activities.
On the following day, ESW participants got a chance to visit three labs in KRISS in accordance with their respective research interest
which are Watt Balance, Quantum Electrical Standard, and LINAC, and had time to seek for deepening research cooperation.
On its final day, participants got some time for in-depth discussion as well as field trip including visit to industries & research
institutes which are closely related to KRISS activities.
To subscribe, please contact: Ms. Jaewon KimPhone: +82-42-868-5445 Fax: +82-42-868-5444 E-mail: [email protected]: http://www.kriss.re.kr/eng Address: 267 Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea
Better Standards, Better Life