Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors
One of the promising directions in oncology is the development of methods for the treatment of malignant tumors with an account of the mechanisms of their genesis and focused on the correction of definite pathogenesis components, while being nontoxic for other organs and tissues. Investigated in thi...
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| Cite this: | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors / N.Ya. Gridina, V.P. Maslov, Yu.V. Ushenin, V.D. Rozumenko, A.N. Morozov // Semiconductor Physics Quantum Electronics & Optoelectronics. — 2020. — Т. 23, № 1. — С. 85-90. — Бібліогр.: 19 назв. — англ. |
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| author | Gridina, N.Ya. Maslov, V.P. Ushenin, Yu.V. Rozumenko, V.D. Morozov, A.N. |
| author_facet | Gridina, N.Ya. Maslov, V.P. Ushenin, Yu.V. Rozumenko, V.D. Morozov, A.N. |
| citation_txt | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors / N.Ya. Gridina, V.P. Maslov, Yu.V. Ushenin, V.D. Rozumenko, A.N. Morozov // Semiconductor Physics Quantum Electronics & Optoelectronics. — 2020. — Т. 23, № 1. — С. 85-90. — Бібліогр.: 19 назв. — англ. |
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| description | One of the promising directions in oncology is the development of methods for the treatment of malignant tumors with an account of the mechanisms of their genesis and focused on the correction of definite pathogenesis components, while being nontoxic for other organs and tissues. Investigated in this work was the possibility of using the phenomenon of surface plasmon resonance (SPR) for the analysis of blood inherent to patients with glioma of different degrees of malignancy by studying the level of aggregation of blood cells. For this aim, we ascertained a correlation between SPR characteristics and the condition of the patient, as well as the choice of the drug's efficient concentration. The works were performed based on positive results obtained in preliminary experiments with lab rats, which were carried out in cooperation with the State Institution “A.P. Romodanov Institute of Neurosurgery, NAMS of Ukraine”, and V. Lashkaryov Institute of Semiconductor Physics, NAS of Ukraine, by using the device “Plasmon”. It has been experimentally shown that, when using the chosen drug by treated patients, the signs of toxic action of verapamil hydrochloride are absent, and the life span is 10 months longer as compared with the group of patients that are not treated with this drug in low concentrations during the postoperative period.
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ISSN 1560-8034, 1605-6582 (On-line), SPQEO, 2020. V. 23, N 1. P. 85-90.
© 2020, V. Lashkaryov Institute of Semiconductor Physics, National Academy of Sciences of Ukraine
85
Optoelectronics and optoelectronic devices
Application of surface plasmon resonance phenomenon for early
detection and determination of the drug concentration
for treating the relapses of malignant tumors
N.Ya. Gridina1, V.P. Maslov2, Yu.V. Ushenin2, V.D. Rozumenko1, � .N. �� r � z� v1
1The State Institution “A.P. Romodanov Institute of Neurosurgery, NAMS of Ukraine”,
04050 Kyiv, Ukraine
2V. Lashkaryov Institute of Semiconductor Physics, NAS of Ukraine, 03680 Kyiv, Ukraine
E-mail: gridinanina@ukr.net
Abstract. One of promising directions in oncology is the development of methods for
treatment of malignant tumors with account of mechanisms of their genesis and focused on
correction of definite pathogenesis components, while being nontoxic for other organs and
tissues. Investigated in this work was the possibility to use the phenomenon of surface
plasmon resonance (SPR) for analysis of blood inherent to patients with glioma of different
degrees of malignancy by studying the level of aggregation of blood cells. For this aim, we
ascertained correlation between SPR characteristics and the condition of patient as well as
choice of the drug efficient concentration. The works were performed being based on
positive results preliminary obtained in experiments with lab rats, which were carried out in
cooperation with the State Institution “A.P. Romodanov Institute of Neurosurgery, NAMS
of Ukraine”, and V. Lashkaryov Institute of Semiconductor Physics, NAS of Ukraine by
using the device “Plasmon”. It has been experimentally shown that, when using the chosen
drug by treated patients, the signs of toxical action of verapamil hydrochloride are absent,
and the life span is 10 months longer as compared with the group of patients that are not
treated with this drug in low concentrations during the postoperative period.
Keywords: surface plasmon resonance, aggregation of blood cells, glioma, diagnostics,
treatment.
https://doi.org/10.15407/spqeo23.01.85
PACS 73.20.Mf
Manuscript received 04.10.19; revised version received 24.12.19; accepted for publication
18.03.19; published online 23.03.19.
1. Introduction
One of the promising directions in oncology is
elaboration of methods for treating the malignant tumors
with account of mechanisms of their development, which
are focused on correction of definite pathogenesis
components and are not toxical for other organs and
tissues. The blood is the internal medium in human
organism, therefore, even small changes in its
homeostatic characteristics have essential diagnostic and
prognostic significance. In full, this can be related to the
complex indices of fluidity and microrheologic
characteristics inherent to peripheral blood cells. To the
microrheologic indices of erythrocytes, one can relate
their deformability and aggregation, the numerical
characteristics of which are the indicators of organism
condition in whole. To the main factors defining
aggregation of erythrocytes, one can relate, first of all,
the charge of their membranes. Lowering this charge
increases aggregation of erythrocytes and is one of the
main factors influencing their sedimentation [1].
It was shown in the recent time that any malignant
process in the human organism is accompanied by tumor-
associated inflammation (TAI) [2–5]. In our previous
investigations, it was ascertained that TAI is practically
absent in benign neoplasms, but arises and begins to
progress when malignant tumors are available [6, 7]. It is
clearly seen in the case of brain glioma progression,
when this glioma transforms from a conditionally benign
condition of the 2nd degree into the condition of the 4th
degree of malignancy, which is characterized by fast
development and results in the patient death for two
years. In this case, malignant characteristics of tumors
are tightly related with availability of TAI.
Thus, determination of the blood cell aggregation
level that defines the 2nd stage of inflammation process of
any origin, including the tumor one, with the aim of early
diagnostics of relapses in the growth of malignant tumor,
SPQEO, 2020. V. 23, N 1. P. 85-90.
Gridina N.Ya., Maslov V.P., Ushenin Yu.V. et al. Application of surface plasmon resonance phenomenon for early …
86
Fig. 1. External look of the device “Plasmon-6”.
with the following correcting them by the individually
selected concentrations of verapamil hydrochloride with
the device “Plasmon”, is a topical task. Innovation of this
approach is that the sensors based on SPR enable to
determine the blood cell aggregation level for a few
minutes, without using any buffer systems and salt
solutions, luminescent or radioactive lables, which allows
obtaining objective results with blood cells. At the same
time, using the calcium channel inhibitors (like to
verapamil hydrochloride) enables to treat patients
without toxical actions on the organism for a prolong
time without interruption of treatment.
The aim of this work was to study the possibility
of using the device “Plasmon” to detect blood cell
aggregation for diagnosing and treating the patients with
glioblastomas in the postoperative period.
2. Biosensors, materials and methods of investigation
Studying the initial processes of blood cell aggregation
was performed using the device “Plasmon-6” designed
and produced in the V. Lashkaryov Institute of
Semiconductor Physics. This device in the real-time scale
displays processes of blood cell aggregation [8–17].
The external look of device (Fig. 1) and its
operation performances are adduced below.
Surface plasmon resonance is a unique optical
surface sensing technique that is responsive to refractive
index changes that occur within the vicinity of a sensor
surface. Thus, SPR can be used to monitor any physical
phenomenon that alters the refractive index at the surface
and has grown into a versatile technique used in variety
of applications. Of special interest is its potential for
biosensing techniques.
The spectrometer “Plasmon” based on the SPR
phenomenon enables to obtain information of optical
properties inherent to the layer adjacent to the gold
surface of the device sensor chip. Changes of the layer
optical properties result in the shift of the SPR curve
(SPR characteristic).
The thickness of layer, which is sensible for this
spectrometer is close to 0.2 � m. At the same time, for
example, the sizes of erythrocytes reach 6.2–8.2 µm.
Therefore, the SPR characteristic of device depends both
on the quantity of blood cells in the sample and on their
mutual position (“coin columns”), which, in their turn,
depend on the properties of membranes.
Earlier, using the SPR method researchers carried
out investigations of reaction “antibody – antigen”, but
later there arise the works aimed at ascertaining the
mechanisms of blood coagulation as well as other tech-
niques. The method providing determination of the blood
cell aggregation degree was not used by somebody and
for the first time was developed by the authors [12].
The performed analysis of commonly adopted clinic
characteristics of erythrocyte sedimentation rate (ESR)
and quantitative composition of blood cells showed that
in the case of brain gliomas these characteristics do not
practically differ from those of normal condition
(Table 2). Except the characteristics of total erythrocyte
number, which with increasing the aggregation degree
tend to group in the so-called “coin columns” that occupy
a smaller substrate area for a larger amount of cells as
compared to the normal erythrocytes of healthy persons.
This fact lies in the background of the method for
determination of the blood cell aggregation degree with
SPR (Table 2).
As known, aggregation or agglutination of blood
cells results in lowering the ratio of surface area inherent
to cell particles to their volume. In this case, the total
amount of cells can be larger, while the area of contact
with the gold film can be less, which leads to the
decreased SPR characteristics [12].
The adduced examples are indicative of a straight
dependence between the degree of filling the sensor chip
and SPR characteristics.
Blood erythrocytes (Figs 2A and 2D) are
represented by the rounded lumps filling practically all
the field of microscope.
In Fig. 2 (B and E), the erythrocytes have the
external appearance resembling the coin columns typical
for many pathologies, in particular, for tumors and
inflammations as well as after addition of 3% solution of
potassium chloride. This solution considerably enhances
Table 1. Performances of the devices of “Plasmon” series.
Refractive index measurement range 1.0 – 1.5
Detection limit of refractive index
variation
0.00005
Angle-of-incidence setting precision,
angular sec
10
Maximum angular scan 17°
Maximum time resolution of kinetics
measurements, s £ 3
Light source, GaAs laser, nm l = 650
Additional ADC input (optional) ±5 V
Overall dimensions of the
measurement unit, mm
215×130×100
Weight 2.5 kg
Computer connect USB
SPQEO, 2020. V. 23, N 1. P. 85-90.
Gridina N.Ya., Maslov V.P., Ushenin Yu.V. et al. Application of surface plasmon resonance phenomenon for early …
87
aggregation of blood cells. As a result, the erythrocytes
adjoin one to another by their biconcave surfaces more
tightly, which promotes creation of coin columns. This
process is reversible. But when adding the reagent anfi-D
(usually used for determination of the blood group) to
this solution, the blood cells agglutinate, and this process
becomes irreversible.
As seen from Fig. 2 (B and E), the chip area
covered with blood cells has many more empty parts as
compared with the case of previous preparation depo-
sited on the glass at the same blood volume (A and D).
The fragments C and F represent the blood cells after
treatment of them with the tsolyclone-A reagent used for
agglutination of the cells related to the respective blood
group. In this sample, the area of empty parts is larger
than that of previous sample (B and E).
The obtained results show that the larger the area of
parts non-filled with the blood cells, the higher the
aggregation (agglutination) degree of blood cells and the
lower the SPR characteristic value.
3. The results of diagnostication and optimization of
treating the patients with application of the
spectrometer “Plasmon”
The life expectancy of patients receiving a course of
treatment with verapamil hydrochloride during a
combined treatment of glioblastomas in the late
postoperative period was shown in Table 3 and Fig. 3.
The initial SPR characteristics of 43 patients included to
observation (11 treated with verapamil hydrochloride and
32 – non-treated) differed only slightly; it is indicative of
adequacy in choosing the groups for investigation. To
choose an optimal concentration of verapamil hydro-
chloride for this treatment, the blood was added with
water solutions of verapamil after dilutions within the
range 1:10 up to 1:100 000. 10-fold verapamil dilutions
resulted in increasing the degree of aggregation, while
the higher dilutions (10 000-fold), by contrast, caused
lowering this aggregation. The verapamil concentration
that corresponded to the strongest lowering the
aggregation degree was then used for treating the patients
with glioblastomas in the postoperative period. The
optimal verapamil concentration for all the patients
turned to be 10 000-fold lower than that commonly
adopted. The patients took this preparation 3 times a day,
continuously, without breaks, for life.
As the criteria of anti-tumor efficiency inherent to
verapamil at low concentrations, we chose the life span
of patients in the late postoperative period.
When using this preparation, the patients had no
signs of verapamil toxic action on organism, and their
life span was by 10 months longer than that of another
group of patients non-treated with verapamil in low
concentrations during the postoperative period.
The SPR characteristic values (corresponding to the
blood cell aggregation degree) in the patients of both
groups are represented in Figs 3 and 4.
Table 2. Clinic characteristics of the amount of blood cells for various neurosurgical pathologies.
Diagnosis
Erythrocytes,
1012/L (n)
Leukocytes,
109/L (n)
Lymphocytes,
109/L (n)
Healthy 4.73 ± 0.33 (9) 5.59 ± 1.32 (9) 2.26 ± 0.44 (9)
Gliomas II 5.14 ± 0.59 (19) 8.46 ± 3.68 (19) 2.04 ± 0.52 (18)
Gliomas III 5.00 ± 0.60 (33) 8.60 ± 3.58 (37) 2.12 ± 0.85 (35)
Gliomas IV 4.88 ± 0.67 (21) 11.38 ± 3.89 (25) 1.99 ± 0.93 (25)
� etastases 4.87 ± 0.77 (7) 10.14 ± 6.29 (7) 1.39 ± 0.53 (7)
Craniocerebral injury 4.31 ± 0.49 (8) 7.81 ± 2.59 (9) 1.81 ± 0.57 (8)
Intervertebral hernias 4.79 ± 0.80 (5) 5.57 ± 0.65 (3) 1.80 ± 0.53 (3)
Note. II, III, IV are the degrees of glioma malignancy; n in brackets – amount of investigated patients.
Table 3. The life expectancy of patients treated with verapamil hydrochloride during the process of combined treatment of
glioblastomas in the late postoperative period.
Group
Number of
patients
Mean
(months)
Standard deviation
(months)
Median life span expected
(months)
Patients, treated
without verapamil –
hydrochloride
32 8.47 1.02 7
Patients, treated with
verapamil –
hydrochloride
8 18.63 1.82 18
SPQEO, 2020. V. 23, N 1. P. 85-90.
Gridina N.Ya., Maslov V.P., Ushenin Yu.V. et al. Application of surface plasmon resonance phenomenon for early …
88
Fig. 3. Surviving data for the first (8 patients) and second (32
patients) groups of patients, who received and did not receive
verapamil treatment, are significant by the Cox’s F-test. The
significance level is 0.00108.
Concentrations of diluted verapamil hydrochloride;
Control – without diluted.
Fig. 4. The ratio of data of blood cells aggregation under action
of verapamil dilutions in patients with glioblastomas, treated
(solid line) and non-treated with verapamil (dashed line). A
comparison was made of SPR data in relation to the data of
blood dilution with water (20 � L of water and 200 � L of
blood).
Fig. 2. Topology of blood cells (magnification ×200) taken from: A and D – the healthy donor; B and E – erytrocytes arranged in the
form of coin columns inherent to many kinds of pathologies or creating as a result of addition of 3% potassium chloride solution;
C and F – blood cells after action of tsolyclone-A (diagnostic monoclone reagent) on them.
SPQEO, 2020. V. 23, N 1. P. 85-90.
Gridina N.Ya., Maslov V.P., Ushenin Yu.V. et al. Application of surface plasmon resonance phenomenon for early …
89
As seen from Fig. 4, lowering the SPR
characteristic values measured in the samples of blood
cells after action of verapamil (10 000-fold water
dilution) is similar to that in postoperative remission
observed for patients with glioblastomas, which is
reliably confirmed by the modern methods of
visualization (magnetic resonance tomography and X-ray
computer tomography). The increase of SPR
characteristic values after action of 10 000-fold diluted
verapamil was observed in patients with recurrent
glioblastoma.
The dependence of blood cell aggregation degree on
availability of the brain tumor was observed when adding
verapamil into the blood, if its concentration
corresponded to 10 000-fold dilution (concentration
10–4). In this case, the absence of relapses coincides with
lowering the SPR values. It is also typical for benign as
well as conditionally benign tumors, such as
meningiomas or gliomas with malignancy of the second
degree [18, 19].
The obtained results agree with the general
tendencies, namely: one of the pathogenetic approaches
in oncology is to apply action directed on lowering the
effects of tumor-associated inflammation that forms
tumor microenvironment promoting the tumor growth or
acceleration of relapses occurrence and creation of
metastases. Using the methods aimed at inhibition of TAI
in the postoperative period acquires considerable interest
within the framework of possible prophylaxis of the
prolonged glioma growth. Most of anti-tumor drugs
possess a number of side effects and cannot be
recommended for long-term using them by patients with
malignant tumors. Inhibition of TAI by application of the
calcium channel inhibitor verapamil promoted the
slowing-down of the glioma relapses occurrence without
any toxical actions on organism during long-term
application. However, with account of the membrane-
modifying action of calcium channel blockers, their
concentration gradient is of essential importance.
Consequently, to choose an optimal anti-tumor effect of
the verapamil inhibitor (defined by breaking the TAI), in
experiments it was necessary to choose its concentration
in vitro with the following application of these results in
treatment of patients to prolong their life span and to
improve quality of life.
Thus, the results of using this innovation approach
for breaking the glioma growth in patients coincide with
those obtained earlier in experiments with lab rats
carrying transplantable glioma (strain 101.8, analog of
human glioblastoma) and are fully confirmed by clinical
tests.
4. Conclusion
The results of investigations performed with patients at
the A.P. Romodanov Neurosurgery Institute, National
Academy of Medical Sciences of Ukraine (Kyiv,
Ukraine) have shown a high efficiency of applying the
method based on using the device “Plasmon” for early
diagnostics and treatment of relapses inherent to
malignant tumors (e.g., glioblastomas). This express
method provides determination of blood cells
aggregation characteristics within several minutes.
When using this preparation, the patients had no
signs of verapamil toxic action on organism, and their
life span was by 10 months longer than that of another
group of patients non-treated with verapamil hydro-
chloride in low concentrations during the postoperative
period.
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Authors and CV
Nina Gridina, Candidate of Me-
dical Sciences, Leading Researcher
at the A.P. Romodanov Neurosur-
gery Institute, NAMS of Ukraine,
Head of the laboratory of experi-
mental neurosurgery. The main
directions of her work are the
study of mechanisms of malignant
progression of gliomas of the brain and methods for
their correction in experiment and in clinical studies.
She is the author of 2 monographs, more than 200
scientific articles and patents.
ORCID: https://orcid.org/0000-0003-1137-8212
Yurii Ushenin got his degree in
Vision and spectroscopy at Taras
Shevchenko National University of
Kyiv in 1971. Since 1973 he
worked at the Institute of Semi-
conductor Physics, NAS of Ukraine
as an engineer and senior researcher
(since 1992 up to now). His area of
expertise includes systems of collection and data
processing, software design (Pascal, Delphi) and
optical devices including SPR and planar semicon-
ducting interferometer.
Prof. Volodymyr Maslov, Doctor
of Materials Science, Head of the
Department of physics and techno-
logical basics of sensor materials
at the V. Lashkaryov Institute of
Semiconductor Physics. Honored
inventor of Ukraine. Author of
more than 156 publications and
more than 400 patents of Ukraine
and USSR author’s certificates. His research interests
include several topics of optical engineering and
physical behavior of functional materials as well as
phenomena of surface plasmon resonance, with
application of it in medicine and ecology.
ORCID: https://orcid.org/0000-0001-7795-6156
Prof. Anatoly Morozov, Doctor of
Medical Sciences (2000), Professor
(2002), Honored Doctor of Ukraine
(1994), Head Doctor at the A.P.
Romodanov Neurosurgery Institute,
NAMS of Ukraine, scientific con-
sultant of the Department of Expe-
rimental Neurosurgery and Clinical
Pharmacology, chairman of the commission for
coordination and regulatory support of clinical trials
under the Presidium of the National Academy of
Medical Sciences of Ukraine (since 2015). The highest
qualification categories in neurosurgery and in the
organization and management of health care. His
research interests include neurotraumatology, neuro-
oncology, social hygiene, healthcare, pharmacology,
and drug standardization.
ORCID: https:orcid.org/0000-0001-7092-4813
Prof. Vladymyr Rozumenko,
Doctor of Medical Sciences,
Professor, Head of the Department
of Intracerebral Tumors at the A.P.
Romodanov Neurosurgery Institute,
NAMS of Ukraine, Honored Doctor
of Ukraine. The main areas of sci-
entific activity: development of new
highly effective methods of surgical interventions for
tumors of functionally significant parts of the brain and
tumors of deep localization using neuronavigation sys-
tems and microsurgical, endoscopic and laser techno-
logies. ORCID: https://orcid.org/0000-0002-8774-6942
|
| id | nasplib_isofts_kiev_ua-123456789-215656 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1560-8034 |
| language | English |
| last_indexed | 2026-03-26T19:16:20Z |
| publishDate | 2020 |
| publisher | Інститут фізики напівпровідників імені В.Є. Лашкарьова НАН України |
| record_format | dspace |
| spelling | Gridina, N.Ya. Maslov, V.P. Ushenin, Yu.V. Rozumenko, V.D. Morozov, A.N. 2026-03-24T12:17:45Z 2020 Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors / N.Ya. Gridina, V.P. Maslov, Yu.V. Ushenin, V.D. Rozumenko, A.N. Morozov // Semiconductor Physics Quantum Electronics & Optoelectronics. — 2020. — Т. 23, № 1. — С. 85-90. — Бібліогр.: 19 назв. — англ. 1560-8034 PACS: 73.20.Mf https://nasplib.isofts.kiev.ua/handle/123456789/215656 https://doi.org/10.15407/spqeo23.01.085 One of the promising directions in oncology is the development of methods for the treatment of malignant tumors with an account of the mechanisms of their genesis and focused on the correction of definite pathogenesis components, while being nontoxic for other organs and tissues. Investigated in this work was the possibility of using the phenomenon of surface plasmon resonance (SPR) for the analysis of blood inherent to patients with glioma of different degrees of malignancy by studying the level of aggregation of blood cells. For this aim, we ascertained a correlation between SPR characteristics and the condition of the patient, as well as the choice of the drug's efficient concentration. The works were performed based on positive results obtained in preliminary experiments with lab rats, which were carried out in cooperation with the State Institution “A.P. Romodanov Institute of Neurosurgery, NAMS of Ukraine”, and V. Lashkaryov Institute of Semiconductor Physics, NAS of Ukraine, by using the device “Plasmon”. It has been experimentally shown that, when using the chosen drug by treated patients, the signs of toxic action of verapamil hydrochloride are absent, and the life span is 10 months longer as compared with the group of patients that are not treated with this drug in low concentrations during the postoperative period. en Інститут фізики напівпровідників імені В.Є. Лашкарьова НАН України Semiconductor Physics Quantum Electronics & Optoelectronics Optoelectronics and optoelectronic devices Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors Article published earlier |
| spellingShingle | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors Gridina, N.Ya. Maslov, V.P. Ushenin, Yu.V. Rozumenko, V.D. Morozov, A.N. Optoelectronics and optoelectronic devices |
| title | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| title_full | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| title_fullStr | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| title_full_unstemmed | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| title_short | Application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| title_sort | application of the surface plasmon resonance phenomenon for early detection and determination of the drug concentration for treating the relapses of malignant tumors |
| topic | Optoelectronics and optoelectronic devices |
| topic_facet | Optoelectronics and optoelectronic devices |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/215656 |
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