Life scienceAs a result of reacting each of them with mouse blood, we observed a change in luminescenceaccording to the concentration of the target. By capturing the emitted luminescence signal w

Medical & healthcare, Drug discovery,
Diagnosis
smartphone
camera and analyzing the images, we demonstrated quantitative measurement
concentration or activity of the target in the blood.

Development of in vitro testing technology using biosensors「Background &proteinsResults」
based on chemiluminescent

Blood tests are widely used in medical examinations as a common in vitro diagnostic m
Department of Biomolecular Science and Engineering, The Institute of Scientific and Industrial Research (SANKEN)
However, there are various detection methods for different blood components, and the amount ofProfessor Takeharu Nagai

Researchmap https://researchmap.jp/ng1

In order to establish a rapid and simple method for blood testing, we attempted to detect bilirub
thrombin in blood using chemiluminescent indicators.

can be minimized because the measurement can be done withgeneral-device such as a smartphone camera. Currently, there is a
We have been developing super bright chemiluminescent ingrowing need for "point-of-care test" that does not limit the places
Bilirubin
is a metaboliteof hemoglobin.
a componentof bildicators for specific detection of biological substancesin blood.
of diagnosis.
By takingUnconjugatedadvantage ofbilirubin
the high(UCBR),
penetration
rate ofbilirubin,thesmartphones
andtheirhighfunctionality,
ourchemiluminescentre“BABI” is a chemiluminescent indicator that binds tothat
is harmful to the human body, is easily elevated in the blood of newborns and causes jau
causative molecule of jaundice in newborn babies, and changes
agents are expected to be used as a point-of-care test method thatits luminescence color from blue to green (Fig.1). Because
Thrombastor"
can easily implement.
it causes anyone
serious symptoms,
such as kernicterus, deafness, and cerebral palsy, UCBR
is an indicator of thrombin, which is important for the progression
factor that need to be monitored. The chemiluminescent indicator BABI, which dof blood coagulation. When digested by thrombin,importantThrombastor
changes its luminescence color from green to blue UCBR,(Fig. 2).changes
As a its color from blue to green when it binds to UCBR (Figure 1). By capturing thisresult of reacting each of them with mouse blood, we observed achange in luminescence color according to the concentration ofthe target. By capturing the emitted luminescence signal with asmartphone camera and analyzing the images, we demonstrated
quantitative measurement of the concentration or activity of the target in the blood.
change with a smartphone camera and analyzing the image components, we succeeded

AbstractLife science

required and the processing method vary depending on the detection sensitivity of the method▍ Background & Results

quantitatively measuring the amount of UCBR in mouse blood.

Blood tests are widely used in medical examinations as a common in vitro diagnostic method. However, there are various deThrombin
tection methods for different blood components, and theamountis a serine protease that plays a central role in blood coagulation, and excessive activof blood required and the processing method vary depending
increaseson
the probability of blood coagulation and thrombus formation. Therefore, the measureme
the detection sensitivity of the method used. In order to establish aofthrombin
rapid and simple method for blood testing, we attempted to detect activity is essential for the prevention of thrombosis such as cerebral infarction abilirubin and thrombin in blood using chemiluminescent indicators.
myocardial infarction. Thrombastor, a chemiluminescent indicator that detects thrombin activi
Bilirubin is a metabolite of hemoglobin. Unconjugated bilirubinchanges
its luminescence color from green to blue when cleaved by thrombin (Figure 2). B(UCBR), a component of bilirubin that is harmful to thehumanbody, is easily elevated in the blood of newborns and causes
jaunmeasuiring the color change by a smartphone camera, we also succeeded in quantitative measureme
Figure 1. Measurement of blood bilirubin concentration with a smartphone camdice. Because it causes serious symptoms, such as kernicterus,ofthrombin
era in plasma.
deafness, and cerebral palsy, UCBR is an important factor
that activity
need to be monitored. The chemiluminescent indicator BABI, whichdetects UCBR, changes its color from blue to green when it binds
to UCBR (Figure 1). By capturing this color change with a smartphone camera and analyzing the image components, we succeeded in quantitatively measuring the amount of UCBR in mouseblood.
Thrombin is a serine protease that plays a central role in blood
coagulation, and excessive activity increases the probability ofblood coagulation and thrombus formation. Therefore, the measurement of thrombin activity is essential for the prevention of thrombosis such as cerebral infarction and myocardial infarction. Thrombastor, a chemiluminescent indicator that detects thrombin activity,changes its luminescence color from green to blue when cleavedby thrombin (Figure 2). By measuiring the color change by a smartphone camera, we also succeeded in quantitative measurement ofthrombin activity in plasma.

▍ Significance of the research and Future perspective

Figure 2. Measurement of plasma thrombin activity with a smartphone camera

The measurement of blood components using chemiluminescent「Signthanificance of the research and Future perspective」
indicators can quickly provide results from a smaller sample
conventional detection methods. In addition, the costTheof testingmeasurement of blood components using chemiluminescent indicators can quickly provide resu

from a smaller sample than conventional detection methods. In addition, the cost of testing canminimized because the measurement can be done with general-device such as a smartphone cameJapanese Patent Application No. 2018-565519, No. 2017-18773
Currently,PCT/JP2018/002591
there is a growing need for "point-of-care diagnosis" that does not limit the places
Japanese Patent Application No. 2018-564671, No. 2017-013463 PCT/JP2018/002587
diagnosis.
By fortakingadvantage
the highofpenetration
rateSensors.
of smartphones
their high functionali
Itoh, Y; Hattori, M; Nagai, T et al. Ratiome tric bioluminescentindicator
simpleand rapidofdiagnosis
bilirubin. ACS
2021; 6(3):and
889-895.
doi: 10.1021/acssensors.0c02000
Tr e a t i s e
our chemiluminescentreagents
are expected
to beused as activity
a point-of-carediagnostic method thHattori, M; Sugiura, N; Nagai, T et al. Ratiometric bioluminescentindicator for a simple
and rapid
measurementof thrombin
using a smartphone.
Analytical Chemistry. 2021; 93(40): 13520-13526. doi: 10.1021/acs.analchem.1c02396
anyonecaneasily
implement.
UR
L https://www.sanken.osaka-u.ac.jp/labs/bse/index.html
K e y w o r d luminescence, diagnosis, smartphone, bilirubin, thrombin
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