1. PERSONALIZED PHARMACOLOGY: from pharmacogenetics to pharmacophotonics
V. Rafalskiy1-2, A. Zyubin3, I.Samusev3, E. Moiseeva1, S. Doktorova1-2
1 - Center of clinical trials, 2 – Medical institute, Laboratory of fundamental photonics and nanophotonics

2. «personalized AND pharmacotherapy»
Dynamics of the number of publications in Medline
«personalized AND pharmacotherapy»
Number of drugs prescribed using personalized pharmacotherapy algorithms (FDA registrations)
THE PERSONALIZED MEDICINE REPORT 2020 · Opportunity, Challenges, and the Future

3. THE CONCEPT OF PERSONALIZED PHARMACOTHERAPY
Biomarker
THE PERSONALIZED MEDICINE REPORT 2020 · Opportunity, Challenges, and the Future

4. OMICs TECHNOLOGY: THE NEW ERA OF BIOLOGY IN MEDICINE
... …
Omics technologies
>

5. LIMITATIONS OF CLASSICAL OMICs TECHNOLOGIES (1)
C. Bedia Experimental Approaches in Omic Sciences In: Comprehensive Analytical Chemistry V. 82,, Pages 13-36

6. LIMITATIONS OF CLASSICAL OMICs TECHNOLOGIES (2)…
Each OMICs technology studies its own narrow segment

7. LIMITATIONS OF CLASSICAL OMICs TECHNOLOGIES (3)
We can easily perform research using one OMICs technology, but it is very difficult to collect information using several OMICs technologies:
technical difficulties
organizational limitations
high cost
Multiomics, pantomics, multiplex analysis etc

8. PHARMACOPHOTONICS
A new scientific field at the crossroads of photonics and pharmacology, focusing on fundamental and applied aspects of the use of optical signal analysis to improve the effectiveness of pharmacotherapy
Assessing the concentration of drugs and their metabolites in body fluids and tissues
The search for physical biomarkers to predict response to pharmacotherapy
Development of new approaches for personalized pharmacotherapy

9. MEDICAL PHOTONICS AND PHARMACOPHOTONICS in Immanuel Kant Baltic Federal University
Laboratory of Fundamental and Applied Photonics. Nanophotonics
Clinical trials center
Medical Institute
Adaptation of Raman spectroscopy and nanophotonics methods for personalization of pharmacotherapy

10. RAMAN SPECTROSCOPY
The method of Raman light scattering provides extensive information on the chemical composition and structure of biological molecules, drugs and their metabolites.
To obtain a Raman spectrum, samples are irradiated with a source of coherent optical radiation (laser). In our studies, a laser with a wavelength of 532 nm was used.
Important features of the method include
Ability to examine a sample without destroying it
Non-contact method of examination
Possibility of quantitative analysis
High specificity

11. RAMAN SPECTROSCOPY vs "OMICs" TECHNOLOGIES
Using a single Raman spectrum of a biological sample, it is possible to obtain information on the structure and/or composition of proteins, nucleic acids, lipids, and on the endpoint concentration of metabolites of low molecular weight substances
in a way the use of Raman spectroscopy provides information that can only be obtained by performing several studies using OMICs technology
Criteria
OMICs technology
Raman spectroscopy
Sample destruction + -
Sample preparation speed
Hours, days
Minutes
Adaptation of the study protocol
Difficult and long
Quickly
Spatial information of molecules in the sample
Information
Requires accumulation and analysis of information
Full chemical information

12. Using Photonics to Optimize Antiplatelet Therapy

13. RAMAN SPECTROSCOPY OF PERIPHERAL BLOOD PLATELETS
Two working hypotheses
Raman spectra of platelets can be used as a biomarker to predict the effectiveness of antiplatelet therapy

14. RAMAN SPECTROSCOPY OF PERIPHERAL BLOOD PLATELETS: a Technique
Deposition of platelet-rich plasma on quartz glass

15. RAMAN SPECTROSCOPY OF PERIPHERAL BLOOD PLATELETS: example of a typical spectrum
Raman spectra of platelets in 400–1750 cm−1 spectral region for healthy individuals
A. Zyubin, V. Rafalskiy 1, A. Tcibulnikova e.a. Dataset of human platelets in healthy and individuals with cardiovascular pathology obtained by surface-enhanced Raman spectroscopy. Data Brief 2020; 29:

16. SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS)
Titanium substrate with applied gold nanoparticles
A. Zyubin, V. Rafalskiy 1, A. Tcibulnikova e.a. Dataset of human platelets in healthy and individuals with cardiovascular pathology obtained by surface-enhanced Raman spectroscopy. Data Brief 2020; 29:

17. SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS)
Thrombocyte
Titanium substrate with applied gold nanoparticles
A. Zyubin, V. Rafalskiy 1, A. Tcibulnikova e.a. Dataset of human platelets in healthy and individuals with cardiovascular pathology obtained by surface-enhanced Raman spectroscopy. Data Brief 2020; 29:

18. SERS SPECTRA OF PLATELETS FOR HEALTHY INDIVIDUALS AND PATIENTS WITH CARDIOVASCULAR DISEASES
SERS spectra of platelets in cm-1 spectral region for healthy individuals (blue line), healthy individuals on antiplatelet therapy (green line) and individuals with cardiovascular pathology (red line).
Intensity of SERS spectra for platelets for healthy individuals (blue line) and individuals with cardiovascular pathology (red line)

19. PROBLEMS OF INTERPRETATION OF RAMAN SPECTRA
Each Raman spectrum contains a huge amount of information
It is necessary to use special tools for analysis - machine learning based algorithms, principal components method, Mehalonobis distance calculation, Borut's algorithm

20. USING THE MAHALANOBIS DISTANCE TO ISOLATE THE INDICATORS OF THE RAMAN SPECTRA WITH THE GREATEST INFORMATIVENESS
The most informative frequency shifts are highlighted:
420
430
485
505
605
615
720
805
955
960
970
975
980
990
1040
1400
1410
1465
1535
1540
1590
Healthy
Healthy + ASA
CVD patients
Patients + antithrombotics

21. Correlation coefficients
SEARCH FOR PHARMACODYNAMIC TARGETS RELATED TO THE CHARACTERISTICS OF RAMAN SPECTRA
Correlations of Raman spectra peak values with platelet activity for different values of frequency shifts. INNOVANCE PFA-200, Siemens
Frequency shifts, 1/nm
Correlation coefficients
PFA Collagen/EPI
PFA Collagen/AD P
PFA P2Y*
420
0,048032
0,013416
0,310134
430
0,047704
0,012992
0,309878
485
0,048681
0,013467
0,312257
505
0,048682
0,014064
0,312937
605
0,049082
0,014239
0,314785
615
0,049225
0,014491
0,314995
720
0,048653
0,016638
0,318294
805
0,052257
0,020117
0,321403
955
0,053559
0,028217
0,324561
960
0,053460
0,028894
0,324808
970
0,053923
0,029046
0,324683
975
0,055187
0,029173
0,324363
980
0,055971
0,028305
0,323754
990
0,060746
0,030599
0,323193
1040
0,054367
0,028248
0,324257
1400
0,059492
0,021467
0,315219
1410
0,059791
0,020449
0,314651
1465
0,055538
0,018451
0,311040
1535
0,054443
0,017188
0,310178
1540
0,057764
0,018988
0,312351
1590
0,061233
0,021042
0,312334
Multiple regression coefficient = 0.31, P <0.05
* - cartridge for the evaluation of platelet dysfunction in the blockade of the P2Y12 receptor.

22. ИСПОЛЬЗОВАНИЯ РАМАНОВСКОЙ СПЕКТРОСКОПИИ ДЛЯ ПЕРСОНАЛИЗАЦИИ АНТИТРОМБОЦИТАРНОЙ ТЕРАПИИ
Предложена и отработана методика и проведена регистрация ГКР-спектров тромбоцитов периферической крови путем использования наноструктурированных титановых поверхностях модифицированных абляционными частицами золота
Показано различие Рамановских спектров здоровых лиц и пациентов с ССЗ
Показана возможность качественной и количественной оценки фармакодинамических характеристик антитромбоцитарных препаратов
Вероятно, изменения рамановских спектров связаны с особенностями функционирования поверхностных рецепторов тромбоцитов, в частности P2Y12

23. Concentration analysis of methotrexate and its metabolites using planar optical sensor and Raman spectroscopy

24. USE OF A PLNAAR SENSOR FOR METHOTREXATE DETECTION

25. OUR PLACE IN THE SPIRAL OF INNOVATION
Point-of-care testing
We here
Prototipe

26. CONCLUSIONS
The most effective development of the direction is possible only at the junction of different scientific disciplines with the participation of scientists of several profiles - pharmacologists, optical physicists, chemists, IT, etc.

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