Factors and levels used in 23 factorial design for extraction and preconcentration of UV filters.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"d9159ce31733bf78cc2a79b18c225994",bookSignature:"Dr. Gabriel Cismaru",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11867.jpg",keywords:"Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Restrictive Cardiomyopathy, Transesophageal Echocardiography, Intracardiac Echocardiography, 3-Dimensional Echocardiography, Adult Congenital Heart Disease, Tetralogy of Fallot, Transposition of the Great Vessels, Coronary Artery Disease, Risk Stratification, Revascularization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 21st 2022",dateEndSecondStepPublish:"May 19th 2022",dateEndThirdStepPublish:"July 18th 2022",dateEndFourthStepPublish:"October 6th 2022",dateEndFifthStepPublish:"December 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Cismaru Gabriel is an Assistant Professor at the University of Medicine and Pharmacy Cluj-Napoca, certified in Cardiology. 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He has authored or co-authored peer-reviewed articles and book chapters in the field of cardiac pacing, defibrillation, electrophysiological study, and catheter ablation.",coeditorOneBiosketch:"Raluca Tomoaia is an MD, Ph.D. in novel techniques in Echocardiography at the University of Medicine and Pharmacy in Cluj-Napoca, Romania., assistant professor, and a researcher in echocardiography and cardiovascular imaging.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"191888",title:"Dr.",name:"Gabriel",middleName:null,surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru",profilePictureURL:"https://mts.intechopen.com/storage/users/191888/images/system/191888.png",biography:"Dr. Cismaru Gabriel is an assistant professor at the Cluj-Napoca University of Medicine and Pharmacy, Romania, where he has been qualified in cardiology since 2011. He obtained his Ph.D. in medicine with a research thesis on electrophysiology and pro-arrhythmic drugs in 2016. Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France, after finishing his cardiology certification with stages in Clermont-Ferrand and Dinan, France. He began working at the Rehabilitation Hospital\\'s Electrophysiology Laboratory in Cluj-Napoca in 2011. He is an experienced operator who can implant pacemakers, CRTs, and ICDs, as well as perform catheter ablation of supraventricular and ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation. He has been qualified in pediatric cardiology since 2022, and he regularly performs device implantation and catheter ablation in children. 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These compounds often contain single or multiple aromatic structures (Figure 1), sometimes conjugated with carbon-carbon double bonds and carbonyl moieties [2]. The presence of these functional groups affords UV filters the ability to absorb photons and rapidly return to the ground state by thermally emitting the energy through vibrational relaxation [3]. This makes the compound to be able to mitigate the deleterious effects of UV radiation [1, 2].
Chemical structures of (a) benzophenone and (b) sulisobenzone.
After application, UV-filters are washed off and enter the aquatic environmental directly or indirectly via wastewater effluent and recreational water systems [4]. They are also used as sun blocking agents in materials such as plastics, adhesive and rubber, this suggests that these compounds can also leach into the environmental matrices [5, 6, 7]. The amount and type of UV-filter used depends on the desired degree of protection, however combined concentrations should not exceed 10% with other organic or inorganic UV-filters [8].
The main concern of the presence of these compounds is their potential toxicity and their effects as xenohormones (effect on reproductive activity) [9, 10]. These effects include estrogenic activity [11], effects on cell proliferation by 4-methylbenzylidene camphor (4-MBC), benzophenones, and octyl methoxycinnamate (OMC) [12]. Several studies have shown hormonal disruption in both in vivo and in vitro test systems in fish and mammals [13, 14, 15, 16]. It has also been recently shown that besides estrogens, there are other hormonal targets affected by UV-filters in fish and mammals [17, 18].
A number of detection techniques have been used to quantify UV-filters in environmental water samples. These include techniques high performance liquid chromatography (HPLC) with UV or mass spectrometry detection [19, 20], HPLC-MS/MS [21], gas chromatography-mass spectrometry (GC-MS) and GC-MS/MS [22, 23]. However, the levels of these compounds in environmental waters are usual in the μg L−1 range. Therefore, sample cleanup/preconcentration techniques such stir-bar sorptive extraction [20], pressurised liquid extraction [1], dispersive liquid-liquid phase extraction [24], solid phase extraction [25], among others, have been used to improve sensitivity, LODs and to remove interferences prior to quantification with the different analytical techniques.
Solid phase extraction is one of the most established preconcentration techniques used for the simultaneous extraction and analysis of organic compounds [26]. Mainly silica bonded phases such as C18 were formerly used for SPE, however recently modified and tuned solid phases can be used to achieve more specificity [27]. Advantages of SPE include the potential of simultaneous extraction, reduced labour and cost. Of the advantages of solid phase extraction, scientists are mostly attracted to the possibility of using reduced amount of organic solvents and the fact that SPE is highly tuneable with regards to the adsorbents used [28].
Thus the aim of this study was to develop a multivariate assisted solid phase extraction method for the simultaneous preconcentration of UV- filters in wastewater samples prior to their spectrophotometric quantification. The main advantage of the method relies on the use of multivariate optimization approach which led to the reduction of the number of experiments and analysis time as well as the use of a simple, fast and cost effective instrumentation. UV-Vis spectrophotometry was chosen due its simplicity and high availability. The factors (such as sample pH, flow rates, eluent and adsorbent types) affecting the preconcentration step method were optimized using univariate and multivariate approach. The developed SPE/spectrophometric method was applied to the preconcentration and determination of two UV filters from the wastewater samples collected from Daspoort wastewater treatment plant (WWTP) in Pretoria, Gauteng, South Africa. According to our literature search there are limited reports on the application of UV-Vis spectrophotometry for quantification of UV filters [29]. In addition, to the best of our knowledge, the application of SPE/UV-Vis spectrophotometry for simultaneous preconcentration and determination of Benzophenone and sulisobenzone has been reported for the first time.
Benzophenone (Reagent plus, 99%), sulisobenzone (5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid) (HPLC, ≥97.0%) and acetonitrile (for HPLC Plus) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Ethyl acetate was purchased from Merck (Merck, Darmstadt, Germany), ethanol and methanol were purchased from Associated Chemical Enterprises (Johannesburg, South Africa). Stock solutions of benzophenone and 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid (10 mg L−1) were prepared in ultra-pure water (Direct-Q® 3UV-R purifier system, Millipore, Merck). Working standards of 100 μg L−1 were prepared daily by diluting appropriate volumes of the stock solution in ultra-pure water. The ion exchange resins used in this study as packing materials were Dowex 1x8 (Chloride form) (Sigma Aldrich).
A Shimadzu UV-2450 high performance single monochromator UV-VIS spectrophotometer (Shimadzu Corporation, Tokyo, Japan) was used for all analysis of the samples. Solid phase extraction (SPE) was carried out in a VacMaster-24 sample SPE station (VacMaster, Biotage, Sweden). The latter was used to control the sample loading and elution flow rate in the range of 1–3.0 mL min−1. An OHAUS starter 2100 pH meter (Pine Brook, NJ, USA) was used for pH adjustments of the reagents and to measure the pH of samples
Influent (after sediment removal) and effluent wastewater samples were collected from Daspoort wastewater treatment plant (WWTP, Pretoria, Gauteng, south Africa). The samples were collected in pre-cleaned 500 mL glass bottles. The samples were then refrigerated at 4°C.
The columns were prepared according to [30]. Briefly, polyethylene columns of diameter 1.0 cm and 6 cm in height were used for preconcentration. Slurries of 0.5 g of Dowex 1x8 in double distilled deionized water were prepared and packed to columns to heights of about 1 cm. A porous frit was placed at the bottom of the column and at the top of the packing material to hold and confine the adsorbent within the designated capacity/volume. The columns were washed with 6 mL of double distilled deionized water followed by conditioning with 3 mL organic solvent (methanol, ethanol, ethyl acetate or mixture of methanol and acetonitrile) and then 3 mL of double distilled deionized water. Due to the scarcity of reference materials for UV-filters, a commercial sunscreen lotion was used as a reference material for the validation of the SPE/UV method. An appropriate amount of the sunscreen lotion was accurately weighed and dissolved using a small volume of methanol (2 mL) and made to the mark with double distilled deionized water and used for validation experiments.
An aliquot (10 mL) of model solution containing benzophenone and sulisobenzone at a concentration of 100 μg L−1 was passed through a packed column at a flow rate of 2–5 mL min−1. After percolating the synthetic samples through, the cartridges were washed with 3 mL double distilled deionised water. Then retained analytes were eluted with 2 mL organic solvents. The optimization of the solid phase extraction method was carried out using a 23 full factorial design involving three variables such as pH, sample flow rate (SFR) and eluent flow rate (EFR). Maximum, central point and minimum levels are presented in Table 1. The second step of the optimization strategy involved the application of a response surface methodology (RSM) based on a central composite design. All the experiments were carried out in random order and the experimental data was processed by using the Minitab 17 software program.
Factors | Low level (−1) | Central point (0) | High level (+1) |
---|---|---|---|
Sample pH | 4 | 7 | 10 |
Sample flow rate (SFR) (mL min−1) | 2 | 3.5 | 5 |
Eluent flow rate (EFR) (mL min−1) | 1 | 2 | 3 |
Factors and levels used in 23 factorial design for extraction and preconcentration of UV filters.
Selection of the adsorbent and eluent type was achieved by packing columns using the ion exchange adsorbent (Dowex 1x8). Each experiment was done in triplicates for each solvent type and adsorbent combination. The flow rates and the sample pH were fixed at 2 mL min−1for both the sample loading and elution and 7, respectively. The results obtained are presented in Figure 2.
Selection of suitable adsorbent and eluent combination in model aqueous solution.
Selection of the adsorbent and eluent was done using the absorbance of benzophenone and sulisobenzone at the wavelengths of 260 and 220 nm, respectively. Since the absorbance is directly proportional to concentration, a higher absorbance can be related to higher concentration. Thus, from the univariate optimization, the most effective adsorbent and eluent combination was found to be Dowex 1x8 and methanol (Figure 2). This combination was further used for the optimization of the solid phase extraction procedure for both benzophenone (UV-01) and sulisobenzone (UV-02).
Due to the overall charge of adsorbents, the extraction and preconcentration of the analytes was possible by means of ionic interactions. Dowex 1x8 has an overall positive charge, thus the negatively charged analytes could interact with the positive charges of the adsorbent. This resulted in higher absorbances and Dowex 1x8 resin was selected as the suitable adsorbent for further studies.
The polarity of the solvent was the contributing factor on the elution of the analytes, the more polar solvent resulted in better elution from the SPE column, and hence higher absorbances for methanol were observed when used in combination with Dowex 1x8. This was a consequence of the methanol having the ability to displace the analytes from the positively charged Dowex 1x8 adsorbent. The 1:1 mixture of acetonitrile and methanol also had promising results, but did not perform better than the methanol alone. Acetonitrile could not be used for this study even though it is more polar than methanol, there are dangers associated with the use of pure acetonitrile like the risk of cyanide poisoning as a result of its decomposition products.
Experimental conditions; mass of adsorbent 0.5 g, sample volume 10 mL at 100 μg L−1, eluent volume 2 mL, pH 7, flow rates 2 mL min−1. MeOH = methanol, ACN = acetonitrile, EtOH = ethanol.
In order to achieve quantitative preconcentration of analytes by SPE system, the optimization of the most influential parameters, such as sample pH, sample and eluent flow rates, was carried out using 23 full factorial design and response surface methodology (RSM) based on a central composite design. Two level full factorial design (FFD), involving 11 experiments was used for screening of the significant factors for the extraction and preconcentration of UV filters. Table 2 presents the factorial design matrix and the analytical responses (expressed as average percentage recovery, %R) obtained in each experiment. Analysis of variance (ANOVA) reproduced in the form of Pareto chart was used to investigate the significance of the effects SPE procedure. The Pareto chart of main effects and their interactions produced are shown in Figure 3.
Expt. | pH | SFR (mL/min) | EVR (mL/min) | UV-01 (%R) | UV-02 (%R) |
---|---|---|---|---|---|
1 | 4 | 2 | 1 | 34.39 | 33.7 |
2 | 10 | 2 | 1 | 39.63 | 39.1 |
3 | 4 | 5 | 1 | 51.01 | 53.5 |
4 | 10 | 5 | 1 | 72.71 | 75.4 |
5 | 4 | 2 | 3 | 12.22 | 16.0 |
6 | 10 | 2 | 3 | 8.84 | 9.1 |
7 | 4 | 5 | 3 | 11.58 | 10.6 |
8 | 10 | 5 | 3 | 10.24 | 17.6 |
9 | 7 | 3.5 | 2 | 83.55 | 72.8 |
10 | 7 | 3.5 | 2 | 78.88 | 77.5 |
11 | 7 | 3.5 | 2 | 81.08 | 78.6 |
Two level (23) full factorial design matrix and analytical response.
Pareto charts of standardized effects for variables in the preconcentration of (A) benzophenone and (B) sulisobenzone.
It can be seen from Figure 3 that for simultaneous preconcentration of UV filters, sample pH and EFR and their interactions were statistically significant. The effect of sample flow rate on the analytical response (%R) was not significant at 95% confidence level. The overall results obtained for the screening step indicated that sample pH and EFR required further optimization. Whereas, sample flow rate was fixed at 3.5 mL min−1.
A central composite design matrix consisting of 14 experiments and analytical response based on each of the experimental runs (Table 3) was used for further optimization of the SPE method. The analysis of variance (ANOVA) of the predicted response surface quadratic model for the recoveries of UV filters was obtained. The ANOVA results were analysed using quadratic equations (not included) for the models to illustrate the dependence of the analytical response with respect to the evaluated main effects [31].
Sample | pH | SFR (mL/min) | EFR (mL/min) | UV-01 %R | UV-02 %R |
---|---|---|---|---|---|
1 | 4 | 3.5 | 1 | 66.1 | 63.4 |
2 | 10 | 3.5 | 1 | 65.7 | 44.5 |
3 | 4 | 3.5 | 3 | 49.7 | 16.6 |
4 | 10 | 3.5 | 3 | 25.9 | 19.2 |
5 | 7 | 3.5 | 2 | 61.3 | 51.9 |
6 | 7 | 3.5 | 2 | 54.8 | 59.2 |
7 | 7 | 3.5 | 2 | 49.7 | 49.7 |
8 | 2.8 | 3.5 | 2 | 78.8 | 49.6 |
9 | 11.2 | 3.5 | 2 | 42.0 | 66.0 |
10 | 7 | 3.5 | 0.5 | 100.1 | 103.1 |
11 | 7 | 3.5 | 3.4 | 32.2 | 17.4 |
12 | 7 | 3.5 | 2 | 75.0 | 81.5 |
13 | 7 | 3.5 | 2 | 74.8 | 82.0 |
14 | 7 | 3.5 | 2 | 75.1 | 81.8 |
Central composite design matrix and analytical response.
The 3D response surface plots (Figure 4) were used to access the interactive relationship between individual variables (sample pH and EFR) and analytical response [31]. Based on quadratic equations and 3D surface response plots, the calculation indicated that pH = 7.5 and EFR = 2 mL min−1 provided maximum retention and recovery of the studied analytes. Therefore, the results obtained from both designs, illustrated that the optimum conditions that led to quantitative extraction and preconcetration of UV filters were 7.5, 3.5, 2 mL min−1 for sample pH, sample and eluent flow rates, respectively.
Response surfaces obtained for (A) benzophenone and (B) sulisobenzone after extraction and preconcentration by SPE.
The effect of pH on the extraction and preconcentration of UV filters can be seen from Tables 2 and 3. Acidic pH resulted in lower recoveries. This is because benzophenone and sulisobenzone have pKa values of 7.5 and 7.6, respectively, meaning that in acidic pH they are more likely to accept H+ ions resulting in lower recoveries as they end up with an overall positive charge. In more alkaline conditions (pH 10), the analytes are easily displaced on the adsorbent, resulting in little or no adsorption.
The central pH (7) showed the highest recoveries for both UV-filters. This is a result of the interaction of the analytes’ negative charge with the positive charges of the adsorbent prior to elution with methanol.
The optimum conditions obtained by the multivariate approach were confirmed experimentally. Under these conditions (7.5, 3.5, 2 mL min−1 for sample pH, sample and eluent flow rates, respectively), quantitative recoveries ranging from 96 to 98.6% were obtained. These recoveries were compared with the predicted recoveries values (95.6 and 98.1% for benzophenone and sulisobenzone) obtained using the RSM model. It was then concluded that the results obtained by RSM model were valid since there was no significant difference at a 95% confidence level between the experimental and predicted values.
Under the determined optimum experimental conditions, the analytical performances of the developed method for preconcentration and determination of UV-filters were investigated. The calibration curves were obtained after a set of standard solutions (0 to 350 μg L−1) was processed using the described SPE procedure. The concentrations of the analytes in the eluent solutions were quantified with the aid of a UV spectrophotometer. The limits of detection and quantification were calculated using the expressions: LOD =
The accuracy of the SPE/UV procedure was evaluated using a sunscreen lotion with a sulisobenzone content of 1.75% (w/w). The recovered sulisobenzone was 1.69 ± 0.07% (w/w) meaning that the percentage recovery was 96.6%. Therefore, the determined values by SPE/UV were in the acceptable range. In addition, the accuracy and matrix effects were investigated by analysing spiked real waste water samples and the results are shown in Table 5. From the recoveries shown in Table 4, it can be seen that the SPE/UV procedure described was not affected by the matrix effects as the recoveries for both benzophenone and sulisobenzone ranged from 99.3 to 100.7%.
Analyte(s) | Matrix | Analytical method | DLDLR (μg L−1) | LOD (μg L−1) | EF | % RSD | Refs. |
---|---|---|---|---|---|---|---|
Octicrylene | Wastewater | MEPS-GC-MS | 0.25–20 | 0.081 | - | 7 | [33] |
Benzophenone-3 | Water | CE-ESI-MS | 300–20000 | 150 | 3400 | 1.5–6.5 | [25] |
Benzophenone-3 | Water | SBSE-LC-MS/MS | 0.005–0.5 | 0.0009 | - | 3–7 | [34] |
Benzophenone-2 | Human serum | DLLME-UPLC-MS/MS | 0.6–40 | 0.2 | - | 1.9–13.1 | [35] |
Benzophenone-3 | Sea water | DLLME-GC-MS | 0.1–0.5 | 0.03 | 262 | <15 | [25] |
Benzophenone | Tap water | DDA-IL-DLLME | 0.002–1.5 | 0.0013 | - | 3.5–5.3 | [32] |
Benzophenone | Sunscreen | SPE-GC-MS | 10–2000 | 4.4 | 25.3 | 4.6–5.5 | [36] |
Benzophenone and sulisobenzone | Wastewater | SPE-UV/vis | 0.50–250 | 0.15-0.28 | 50 and 55 | 3.1–5.2 | Current work |
Comparison of the analytical figures of merit of the current method and those reported in the literature.
MEPS = microextraction in packed syringe, CE-ESI = capillary electrophoresis-electro spray ionisation, SBSE-LC-MS/MS = stirbar sorptive extraction-liquid chromatography tandem mass spectroscopy, DLLME-UPLC = dispersive liquid-liquid microextraction-ultra pressure liquid chromatography, GC-MS = gas chromatography-mass spectroscopy, SPE = solid phase extraction, DDA-IL =double dispersant assisted-ionic liquid, UV/vis = ultraviolet-visible spectrophotometry.
Sample | Added (μg/L) | Benzophenone | Sulisobenzone | ||
---|---|---|---|---|---|
Found (μg/L) | % R | Found (μg/L) | % R | ||
Influent 1 | 0 | 85.8 ± 1.3 | 69.4 ± 1.2 | ||
50 | 135.3 ± 2.3 | 99.3 | 119.7 ± 3.5 | 100.7 | |
100 | 186.3 ± 2.5 | 100.6 | 169.4 ± 4.2 | 100.0 | |
Effluent 1 | 0 | 6.83 ± 0.92 | 19.8 ± 0.9 | ||
50 | 56.7 ± 1.2 | 99.8 | 69.6 ± 1.3 | 99.7 | |
100 | 106.9 ± 3.1 | 100.0 | 119.1 ± 2.7 | 99.3 |
Analysis of wastewater samples (influent and effluent) spiked and unspiked from Daspoort (Pretoria, Gauteng, South Africa) wastewater treatment plant.
As seen on Tables 5 and 6, there was a significant amount of both UV filters on the influent. This can be explained by the fact that the Daspoort waste water treatment plant treats domestic waste water. Therefore as explained by [37], personal care products are usually applied to the skin and later washed off into drains which are connected to wastewater treatment plants. From wastewater treatment plants, the water is discharged into rivers [3]. This has resulted in the occurrence of UV-filters in surface waters [22], sediments [38, 39], drinking water and even fish [4, 12, 40].
Samples | Months | Benzophenone | Sulisobenzone | ||
---|---|---|---|---|---|
SPE/UV | SPE/HPLC | SPE/UV | SPE/HPLC | ||
Influent | August | 78.6 ± 1.2 | 79.4 ± 1.5 | 56.3 ± 2.1 | 58.0 ± 1.8 |
September | 155.3 ± 2.4 | 157.2 ± 2.2 | 171.3 ± 3.1 | 172.2 ± 2.8 | |
October | 327.3 ± 4.3 | 328.9 ± 4.0 | 337.3 ± 3.6 | 337.6 ± 3.6 | |
Effluent | August | 18.5 ± 0.7 | 19.5 ± 0.5 | 14.5 ± 0.7 | 15.1 ± 0.5 |
September | 57.9 ± 1.3 | 59.0 ± 1.5 | 23.6 ± 0.9 | 24.2 ± 0.8 | |
October | 134.5 ± 1.5 | 135.1 ± 1.2 | 45.3 ± 0.5 | 46.0 ± 0.2 |
Analysis of influent and effluent over from Daspoort (Pretoria, Gauteng, South Africa) wastewater treatment plant a period of 3 months.
The presence of UV-filter in different water bodies does not only have an effect in humans as suspected endocrine disrupters [18]. Their effects spans into aquatic life, as reported by [3], benzophenone can cause cell membrane impairments in fresh water protozoa. Benzophenone was also found in other fresh water species in percentages ranging from 50 to 80% by [41].
The described method was applied in the analysis of real water samples collected over a period of three months as expressed in Table 6. The influent and effluent samples were collected over two seasons, namely winter (one month) and spring (two months). From Table 6, it was observed that between the three months, October showed the highest concentrations for both the influent and effluent. This was because it was significantly warmer during spring when compared to August. It is also worthy to note that the concentrations of benzophenone were higher than those of sulisobenzone. This could be the consequence of the degradation of sulisobenzone during the water treatment process. This is possible because benzophenone forms the backbone of sulisobenzone, this means that when the sulisobenzone losses the methoxy and sulfonic acid side chains, traces of the benzophenone can remain in the water.
The described SPE/UV procedure was compared with a reference method, SPE/HPLC method using the same extraction conditions. The obtained results from the SPE/UV methods were comparable with the SPE coupled with HPLC method. According to the paired student t-test, there was no significant difference between the two methods at 95% confidence level. Therefore, the SPE/UV procedure can be utilised as a rapid, cheap and effective method for the determination of UV-filters in water samples.
The combination of SPE and UV-Vis spectrophotometry offers a simple, inexpensive and selective procedure for the assessment of UV-filters in wastewater samples. With the aid of multivariate optimisation of key parameters in the solid phase extraction procedure, it was possible to achieve satisfactory analytical performance. Real sample analysis showed that as explained by [27], wastewater treatment plant processes are not exhaustive enough to completely remove emerging organic pollutants. There were still some traces of benzophenone and sulisobenzone found in the effluent which is released into the nearby river. This means that the flora and fauna in the river is exposed to these potentially toxic compounds. Thus, the next step would be to study the distribution of these UV-filters in the river where the effluent is released into.
The authors wish to thank National Research Foundation (NRF, South Africa, Grant No. 99270) for financial assistance.
Organoids are miniature 3D models of
Organoid formation from stem and progenitor cells. Following tissue dissociation, adult stem cell/ progenitor cells from normal or patients are isolated. Induced pluripotent stem cells (iPSCs), embryonic stem cells and adult stem cells are subjected to guided differentiation, followed by growing them on extracellular matrix in 3D culture system using specific culture media to begin organoid culture. The lower right section shows the different aspects of organoid commercialization, including molecular profiling of the collected cells, long term storage of cells with appropriate patient consent and information. These biobanked organoids can then be used for functional studies related to potential applications like disease modeling, therapeutic development, regenerative medicine, toxicology, and personalized medicine.
Tissue specific organoid bioenginnering and different basic biomedical and commercial applications.
Backed by some significant observations in the proliferative nature of adult tissue stem cells in 2009, the cardinal notion enveloping organoid technology is that stem cells have ingrained potential to self-assemble into 3D constructs with similitude with human organs [5]. As time rolled on, the modus operandi has been implemented to produce several human and murine organoids out of epithelial tissues of various organs such as the liver, intestine, kidney, skin [6, 7, 8, 9]. Another breakthrough entails the evolution of organoids obtained from induced pluripotent stem cells (iPSC), which can circumvent the toil to avail specific tissues like the heart or brain. This prodigious prospect, reinforced with genetic engineering, permits the mutational corrections in patient-derived iPSCs expediting differentiation to generate a specific type of cells [10, 11, 12, 13]. Scrupulous experimental manipulation while maintaining sensitive biological complexity allows organoid technology to bridge the gap between 2D cell culture and 3D models [14]. It has also proved to better simulate human physiology than animal models and has shown the promise to substitute animals in preclinical biology [15, 16].
As ratiocinated from the trends, there will be a steady increase in the demand for organoid technology in the following years [3, 16]. As per reports published in various media, around 20 companies are into business with this technology—their activities include biobanking, manufacturing, commercialization, the implication of robotics for the development of organoids, organoids on a chip, etc. Statistically, priorities are given to heart, brain, intestine, and kidney organoids [3]. Financial models adopted by these companies are—(i) venture capitals, (ii) partnerships (iii) direct collaboration with the originators. Routine use of animals for disease modeling has always been afflicted with stringent moral and ethical queries. Usage of embryonic stem cells has also faced stormy skirmishes regarding the moral status of the embryos. Likewise, the moral and legal status of the organoids has been called in regulatory questions, to mention a few—ownership, consent, IP rights, safety, commercialization, etc. Utilization of ‘matrigel’ (extracellular matrix obtained from animals) has raised some safety concerns regarding compatibility with the human system. The debate revolving around the exchange or donation of human tissue as a commodity is still ongoing. To resolve this, few regulations should be declared and accepted by the global intellect [17]. Quibbles for intellectual property (IP) generation with human tissue should cease to persist, showing proper dignity and preserving the donor\'s rights. Consent should become a requirement avoiding de-identification of the donor [18, 19, 20, 21]. In the present chapter, we shall highlight the usage of the organoid, organoid cell atlas, followed by shedding light on the commercialization aspect of the technology and future directionality.
Researchers traditionally used
With the advent of tumor organoid culture, patient-derived tumor organoids (PDTOs) have become popular tools to study molecular tumorigenesis, understand tumor heterogenity, predict drug responses, immunotherapy, and precision cancer therapy. At the moment, several tumor organoid biobanks have been developed catering to a variety of cancer types, including lung [31], breast [32], gut [33], and brain [34], liver [35], colorectal [36], pancreas [37], prostate [38], and ovary [39]. The role of tumor immune microenvironments (TIME) is significant in improving cancer immunotherapies, and PDTOs have started playing a crucial role in modeling the tumor-immune landscape. PDTO-based TIME studies can help evaluate immunotherapies such as checkpoint inhibition and adoptive T-cell treatment [4]. Thus, optimizing the tumor organoid culture method is critical for developing organoid-guided customized cancer immunotherapy [40].
Human organoids are suited for genetic modification and customization and bridge the gap between fundamental research and clinical practice. This technique has aided oncology, biological, pharmacological, regenerative, and personalized medicine studies [1]. Despite the initial advances, the technology is still nascent and is expected to be employed in various applications such as developmental and stem cell biology, toxicology, drug discovery, personalized medicine, disease modeling, immune interaction, and regenerative modeling (Figure 2). Healthy human organoids from different tissues may be utilized to test comparative therapeutic toxicities in combination with disease-related organoids. Cardiac organoids, liver organoids, kidney organoids, and other organoids are now used to dictate intolerable adverse effects, such as hepatotoxicity, cardiotoxicity, nephrotoxicity, and other tissue toxicity [41]. Patient-specific relevant organotypic models will go a long way in reframing basic findings, testing innovative ideas in 3D, and validating crucial data without sacrificing animal life for science. This aspect is dealt with in other publications [42, 43].
The lack of a physiologically relevant model system has delayed the therapeutic development process, and many candidates have failed in clinical trials [4]. Cancer organoids are near-physiological replicas of their parent tumors and bridge the gap between drug screening and clinical trials. Organoids have been utilized to examine personalized cancer patient responses in several research [32, 44, 45]. It may also be utilized to look at the epigenetic and genetic changes that cause drug resistance [46]. Tumor organoids can accurately predict chemotherapeutic response and resistance for certain drugs in some cancers [47, 48]. Finding the right therapeutic combination can be a challenge, and tumor organoids can help solve this dilemma and can make personalized medicine a reality [49]. The advances in genetic engineering technologies like CRISPR-Cas9 are implemented on organoids further to confirm medication sensitivity to specific mutations [50]. Organoids may also be used for pharmacokinetic research, critical in drug development. Results suggest that drug-transporters, their efflux transport functions, drug-metabolism can be efficiently studied using organoids [51]. In addition to cancer biobanks, organoids have a significant role to play in immunotherapy, a kind of cancer treatment in which the patient\'s immune system is used to eliminate tumor cells [52]. Organoid-based models are explored to study the effect of tumor-immune cell interaction using a coculture system with both components [53].
Organoids holds promise as a propitious platform in biomedical research and applications for many decades to come. Human organoids currently have a few limitations that require to be circumvented to appreciate their full potential. Some technical and conceptual limitations may be addressed using single-cell sequencing and spatial profiling. Single-cell transcriptome/ epigenome sequencing and spatial profiling can provide a thorough idea about the composition of cells and the state of cells present within the organoids, which may help develop organoids as futuristic models of human biology. In combination with the Human organoids and single-cell technology, a pilot project has been launched within the Human Cell Atlas (HCA) as a “Biological network” (https://www.humancellatlas.org/euh2020/) [54]. HCA is a revolutionary global collaborative initiative aiming at advancing biomedical research opportunities and therapy using single-cell technologies (https://hca-organoid.eu/). This pilot project, under HCA, focuses on the single-cell characterization of organoids and other complex
It is one of the six pilot projects funded by the European Union (EU) Horizon 2020 Framework Programme, which will be helpful in developing the first version of the Organoid Cell Atlas, which may be used as a nucleus for a broader, collaborative, global initiative. The HCA-Organoid association has eight partner Institutions, including EMBL’s European Bioinformatics Institute institutions having experts in organoid technology, single-cell profiling, advanced imaging, and bioinformatics from Austria, Germany, the Netherlands, and Switzerland, and received €5 million by EU funding, as a part of the European contribution to the HCA project. Currently, the project mainly focuses on generating single-cell transcriptome, epigenome maps, and detailed imaging data in a selection of human organoids. The initial objective of the funded project is to derive and characterize two organoids, colon and brain, from 100 whole-genome-sequence individuals each, to have a record of normal population variation and have a reference for disease-centric research [56].
The colon and brain organoids were one of the first organs to which organoids were demonstrated, so comparatively, more advanced protocols for the two are available with HCA [2, 23]. Apart from this, the colon organoids are derived from adult stem cells while the brain is from the iPSCs, thus spanning the two primary sources of organoid derivation. Both of them have primarily been used for disease-centric studies. If the single-cell characterization of these organoids is done for many individuals, this can help facilitate various biomedical applications. Beyond the initial target, most of the data information in the project is generalized in a way to be applicable to various other types of human organoids. The HCA has also spoken about the possibility that they can collaborate with other institutes for different projects, which can pursue systematic single-cell profiling in other types of human organoids, to explore the possibility of interrelation with the Organoid Cell Atlas [56].
The main aim of the EU H2020 HCA-Organoid project is to build an Organoid cell atlas portal that may be equipped with the computational infrastructure and a web-based front end that makes the data easily accessible and analyzed. Some of the organoid-specific features that have been focused on while developing an Organoid portal include the interactive exploration of human organoid data, data-driven selection of organoids for functional experiments, and comparison of disease-specific organoids against reference collections of normal organoids.
This portal also focuses on providing the data of the corresponding primary tissues available in the HCA and also will work on showing interactive mappings between single-cell profiles of human organoids. These may be achieved using the algorithms that enable cell-cell alignments between these datasets. This portal is supposed to facilitate the use of organoids in biomedical experiments and encourage the use of organoids as models in various experiments like precision medicine, drug development, disease modeling, etc. Mapping and data integration may detect normal variation between individuals in an interactive manner showcasing organoid as the capable model for the corresponding variation in primary tissues. The analysis and interpretations of disturbances in the human organoids related to the primary tissues will be performed using cell-cell alignments [56].
A set of strategies have been laid to develop the atlas to be most productive and of high quality. Initially, it was thought to invest in validation and standardization for organoid-related research. Later, a contribution towards the HCA to establish community standards and software infrastructure for data processing and data annotation was strategized. Then the development and validation of computational methods for the comparison of cells between organoids and corresponding primary tissues and their flexible alignments were implemented. Finally, the implementation of interactive visualization tools that helps in establishing user-friendly quality control and exploratory analysis of single-cell organoid datasets contributed to the Organoid Cell Atlas [55].
With the development and successful commercialization of organoids, the most demanded sector in treating patients and pre-clinical trials in pharmaceutical industries will give a slanting graph in the market in the future [57]. In this present era, many specific and most suitable techniques have been developing over the years for organoid research, leading to competition among industries worldwide. The annual cost of treating brain diseases in Europe is $798 billion, and globally it amounts to $3 trillion. Over 90% of novel drugs that are being developed for brain diseases fail during the developmental process, which further reinforces the scope and opportunities for organoids [2]. The development of the living human brain (LHB) enables culturing of human-derived brain organoids from the cells of any individual; the University of Helsinki provides a new technical idea for preclinical trials of drugs in this area. Helsinki Innovation Services Ltd (HIS) supports the commercialization projects of the University of Helsinki from the funding application stage to completion.
Many startups such as XILIS, CELLESCE, SYSTEM1 BIOSCIENCES, 3DYNAMICS, PATH BIOANALYTICS, KNOWN MEDICINE, CYPRE, DYNOMICS are currently working in the domain of organoid technology. XILIS is developing a patient-derived miniature organoid technology to upgrade precision medicine and pharmaceutical drug discovery; their needed materials lead to 30× speed, 50× throughput, and 300× cost-saving (Hans Clever includes in the founding team of XILIS). CELLESCE is a UK-based startup that invented a bio-processing technology intended to grow and expand organoids in drug discovery and regenerative medicine. $25 million of Series A venture funding is raised in SYSTEM1 BIOSCIENCES incorporation with Charles River Ventures and Pfizer Ventures, upgrading neuro drug discovery through the combined action of human brain models, scaled biology, and machine learning to interpret brain disease from genetics to neural computation. Also, KNOWN MEDICINE raised a total of $2.4 M from Khosla, Cota Capital, and Y-Combinator, offering cutting-edge biology research and the latest AI techniques, giving oncologists an easy spot for treating patient\'s tumors with the best suitable drug. PATH BIOANALYTICS does bioanalysis of Phenotypic drug discovery and development. CYPRE is developing a tumor model platform intended for transformative 3D cellular research and clinical testing of cancer patients with seed funding from Hemi Ventures and others. DYNOMICS received $500K in pre-seed funding from Boost VC. The details of the organoid-specific startups are presented in Table 1. These different startups contribute a vast platform to save millions of people’s life [58]. Several companies are also operational in the tumor organoid domain, like Charles River and CROWNBio.
Company name | Country | Application area |
---|---|---|
XILIS INC. | Durham, North Carolina, USA | Micro-organospheres |
CELLESCE | Wales, UK | Patient-derived organoids (PDO) |
SYSTEM 1 BIOSCIENCES | San Francisco, CA, USA | Brain organoids |
3DNAMICS | Baltimore, Maryland, USA | Brain and liver organoids |
PATH BIOANALYTICS | North Carolina, USA | PDO for precision medicine |
KNOWN MEDICINE | Salt Lake City, Utah, USA | Patient-specific organoids for cancer drug development |
CYPRE | San Francisco, CA, USA | 3D tumor model |
DYNOMICS INC. | San Francisco, CA, USA | Human cardiac organoid |
CHARLES RIVER | Wilmington, MA, USA | Tumor organoid |
CROWNBio | San Diego, CA, USA | Tumor organoid |
The current leaders in the commercialization of organoids, their geographical location, and application areas.
Despite using pre-clinical trials in animal models, concerns are raised about whether the animals will be extinct if used over the years. This will lead to the depletion of species and a significant effect on the ecosystem. Moreover, they may lead to harmful effects on the environment once mutated and released. The Animal Welfare Act of 1970 was implemented in the United States and set standards for animal use and care in research. Three principles of the Act are (1) experiments must be proven necessary for instruction or to save or prolong human life, (2) animals must be appropriately anesthetized, (3) animals must be killed as soon as the experiment is over. Much to our intrigue, different types of organoids such as kidney organoids, lung organoids, liver organoids, intestine organoids, brain organoids, etc., can substitute such animal models in preclinical trials for drug discovery and precision medicine. Even self-organ plantation may occur with the continuous development of organoids.
Globally, the expenses of organ transplantation and post-transplantation maintenance treatment are quite expensive but varies according to variables such as geographical location, medical facility, transplant organ type, and access to insurance coverage [59]. Private hospitals in India now charge around INR 10 lakh to INR 30 lakh for a heart transplant, while in USA, the charges can be very high ~$1,664,800.00 (https://www.statista.com/statistics/808471/organ-transplantation-costs-us/). While the cost of a kidney transplant goes from INR 5 lakh to INR 20 lakh, while in USA it can be around ~$442,500.00. The cost of a liver transplant runs from INR 15 lakh to INR 35 lakh, and ~$878,400.00 in the USA. The eventuality of the unaffordability of such expensive treatment modalities led to the demise of a multitude. Furthermore, organ transplants from other donors are sometimes associated with organ rejection and the onset of auto-immune disease. It is not only the high cost of transplant but also the availability and transport of organs is a major issue in many countries. Though the number of donors have increased but the needs have also reached new heights [59]. One-third of all organ transplants fail due to rejection due to multiple reasons including HLA mismatch and alloantibodies [60]. While modern medicine has halted acute rejection but chronic rejection is a major challenge. The organoid technology may provide a realistic patform to design transplantable tissues in a dish thereby catering to the transplant problem in the near future as current limitation prevent organoids from meeting these expectations.
Another recent scientific area where organoids showed great potential was during the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. SARS-CoV-2 causes respiratory illness and multi-organ dysfunction. Scientists were scrambling to test experimental COVID-19 systemic medicines. Organoids were used to study the adverse effects of SARS-CoV-2 infection on human tissues and for the investigation of prospective therapeutic approaches. With the recent work on mini lungs organoids, a few of the drugs stemmed from the infection of the organoid models, representing a handful of possible treatments for COVID-19 [26]. Scientists must still develop methods to produce more complicated systems, such immune cells and blood arteries, to fully harness the technology [26]. Scientists must also find a way to swiftly and inexpensively produce thousands of identical organoids. Bioprinting is a potential new fast prototyping method that prints cells and accompanying matrices in 3D. Organoid bioprinting uses hydrogel-based bioinks to deposit various cell types that stimulate physiological signaling and can help commercialize the platform faster [61].
According to a study published by Fior Markets, the global organoids, and spheroids market is predicted to increase from USD 502.92 million in 2019 to USD 2794.79 million in 2027, with a CAGR of 23.91% from 2020 to 2027 [57, 62]. Till now, 19 companies are having an interest in organoid commercialization. Some of them are Thermo Fisher Scientific (Waltham, MA, USA), Merck (Kenilworth, NJ, USA), Corning (Corning, NY, USA), STEMCELL Technologies (Vancouver, Canada), Lonza (Basel, Switzerland), Prellis Biologics (San Francisco, CA, USA), Amsbio (Abingdon, UK), Cellesce (Cardiff, UK), DefiniGEN (Cambridge, UK), OcellO B.V. (Leiden, Netherlands), HUB Organoid Technology (Utrecht, Netherlands), 3Dnamics Inc. (Baltimore, MD, USA), Organoid Therapeutics (Pittsburgh, PA, USA), InSphero (Schlieren, Switzerland), etc. Organome (Baltimore, USA) and HUB (Hubrecht Organoid Technology) are dedicated to organoid biobanking, and other companies aim at manufacturing, organoid marketing, other related technologies. SUN Biosciences (Lausanne, Switzerland) and System1 Biosciences (San Francisco, CA, USA) use robotic automation tools for organoid generation. The semi-automated process enabled researchers to make retinal organoid production and selection faster using the algorithm. The MIMETAS (Leiden, Netherlands)—the organ-on-a-chip company, offers the second-best cell-based model after humans, using human cells growing in three-dimensional structures called Mimetas’OrganoPlates (microfluidics-based culture plates allowing culturing and screening of a range of organ and tissue models), which are affordable and available for nonspecialized end-users. With a consumption market share of about 46% in 2019, North America is the most important consumer of organoids, with Europe in second place. Key manufacturers of the global organoids market are Thermo Fischer Scientific, Merck, and Corning. The top three players took up a market share of about 75% in 2019. Byers of the report can access verified and reliable market forecasts, including those for the overall size of the global organoids’ market in terms of revenue. The Organoids’ market is segmented into 3D Organoid Culture and Biochemical Cues. In the case of Organoids application, the leading players are Biopharmaceutical Companies, Contract Research Organizations, Academics, and Research Institutes. The regional analysis covers North America (USA, Canada, and Mexico), Europe (Germany, France, UK, Russia, and Italy), Asia-Pacific (China, Japan, Korea, India, and Southeast Asia), South America (Brazil, Argentina, Columbia, etc.), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria, and South Africa) and predicts an upsurge in the usage of organoid technology across the globe in future.
Organoid Biobank is like a commercial bank with a similar modus operandi. In organoid biobank, collected samples from different sources such as stem cells, primary tissues, and biopsies were made into organoids and stored. The organoid samples can be taken from a healthy individual and a patient. These stored organoids are ready to use for different purposes. Organoid biobanks manage the database of organoids and a registry with all the patient details. These stored organoids can be tracked and used for wireless phenotyping with the help of radio-frequency identification (RFID) ultracompact chips inserted within them. The organoid biobanks store and transport organoids using liquid nitrogen.
The regulatory rules for organoid research use and commercialization are not very well laid in many countries and needs an update. The scientific, ethical, and regulatory problems related to organoid research are subject to extensive regulatory scrutiny and controlled partly by federal laws and state laws in the US and pertain to International laws in case of foreign collaborations. United States Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) regulations are implemented in organoid research [63, 64, 65]. Organoid research is subject to the Institutional Review Board (IRB) approvals. Many institutions have Embryonic Stem Cell Research Oversight (ESCRO) or Stem Cell Research Oversight (SCRO) committees that oversee research utilizing human ESCs or iPSCs. These committees are outlined in the National Academies Guidelines for Human Embryonic Stem Cell Research and help evaluate the scientific and ethical aspects. The special committees assess the current state of research, weigh the advantages and hazards, address related ethical problems, including informed consent from the donor, and evaluate suitable supervision methods as per the federal guidelines [63].
While in Europe, organoids research must be approved by the Research Ethics Committee (REC) as per the guidelines laid down by the European Medicines Agency (EMA). Different European countries also have their individual regulatory agencies. In India, the regulatory board is the Institutional Committee for Stem Cell Research (IC-SCR). At the same time, in China, the measures for Ethical Review of Biomedical Research Involving Human Subjects and Ethical Guidelines for Human Embryonic Stem Cell Research, are used as guidelines [66]. The manufacturing process of organoids for commercial purpose must fulfill the same standards as other pharmaceutical drugs, following good manufacturing practices (GMP) [64, 65]. Additional hurdles exist at the convergence of organoid technology and commercial clinical use, global rules relating to the heterogeneity of approved quality standards, privacy laws and data protection, patent laws and identifying ownership. As a positive step in this direction, the International Society for Stem Cell Research (ISSCR) has set new stem cell research guidelines in 2021 [67, 68, 69]. It is expected that organoid-based biotechnology innovations would need updated global regulatory guidelines and governance in the future.
Organoid technology and biobanking have grown in recent years, paralleling the expansion of stem cell and organoid research. However, ethical, moral, and legal existential questions persist. One crucial aspect is establishing globally recognized consent procedures for research and clinical organoid biobanking protocol. Also, the ethical and moral implications for clinicians while using organ mimics should be called into question. Patenting concerns are bound to arise when organoids are distributed over the world. Collaborations between the public and commercial sectors may lead to data exchange, entitlement sharing, etc. Confidentiality decorum and global patenting rules for organoid rights are therefore evolving. Even the iPSC-based organoids bring new concerns around permission, commercialization, ownership, IP rights, safety, and marketing [70]. The proliferation of big data, genomics, biobanking, and the globalization of the biotechnology sector has complicated the task of setting universal ethical standards. The primary ethical consideration about organoids is who owns them and whether small organ mimics (similar to organs) can be traded? With the advances in organoid technology, where do we draw lines to differentiate between organoids and tissues/organs? Sample de-identification, donor consenting, and licensing rights need to be better defined, especially concerning organoid commercialization. Addressing these bottlenecks may allow quicker commercial application for drug discovery, disease modeling, and research and development.
In the upcoming years, the designed pilot project focuses on substituting animal or human models with the organoid model by encouraging better research and accessibility of organoids. The HCA has been encouraging this shift of models by establishing a reference map of the entire human cells; which will be the first molecular picture of a human that will help the researchers to functionally dissect and systematically analyze human biological systems that would lead to a better exploration of organoids as a model. The initial version of the organoid cell atlas is planned to be established by the upcoming year that will be practically useful and open to advancements. These are thought to help maximize the impact of the project to become helpful in the field of basic biology and biomedical applications. To broader the reach, the single-cell profiles will be made public as soon as possible following HCA\'s ethical, social, and legal guidelines. Finally, the Organoid Cell Atlas Portal will be made “into a public, sustainable and widely used infrastructure for finding, accessing, analyzing and interpreting single-cell data from human organoids.” The goal of the Organoid Cell Atlas is to make advancements in the biomedical field and develop various regenerative therapies by encouraging and accelerating disease-centric research of rare genetic diseases, precision oncology, or other complex diseases that are yet less understood. So, to achieve all of their objectives, they have made the portal open to create an inclusive research environment that would help in collaborating with a broad range of researchers interested in the field, which would later lead to extremely well-defined growth in the field of organoids.
M.K.P. acknowledges S. Dubinett, B. Gomperts, and V. Hartenstein for providing constant support and mentoring.
The authors declare no conflict of interest.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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