Phenolphthalein-Conjugated Hydrogel Formation under Visible-Light

Subscriber access provided by Kaohsiung Medical University

Letter

Phenolphthalein-Conjugated Hydrogel Formation under Visible Light Irradiation for Reducing Variability of Colorimetric Biodetection Seunghyeon Kim, and Hadley D. Sikes ACS Appl. Bio Mater., Just Accepted Manuscript • DOI: 10.1021/acsabm.8b00148 • Publication Date (Web): 12 Jul 2018 Downloaded from http://pubs.acs.org on July 14, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Applied Bio Materials

Phenolphthalein-Conjugated Hydrogel Formation under Visible Light Irradiation for Reducing Variability of Colorimetric Biodetection Seunghyeon Kima and Hadley D. Sikesa, b* a

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

b

Program in Polymers and Soft Matter, Massachusetts Institute of Technology, Cambridge, MA 02139, USA *E-mail: [email protected]

Keywords: colorimetric detection; dye leaching; polymerizable phenolphthalein; dye-conjugated hydrogel; visible light-induced polymerization

ACS Paragon Plus Environment

1

ACS Applied Bio Materials 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 15

Abstract

Polymerization-based signal amplification (PBA) is a colorimetric biodetection method for use in resource-limited settings. It uses phenolphthalein as a colorimetric reagent, but leaching of the dye from a resultant hydrogel can lead to variability in PBA results. In this work, we use polymerizable phenolphthalein in PBA to produce a phenolphthalein-conjugated hydrogel. Considering the photoinitiation mechanism of eosin Y and triethanolamine in air with an aqueous monomer solution, we determine reaction conditions for modified PBA that maintain a rapid polymerization response. Using the optimized conditions, we demonstrate that modified PBA can detect malaria antigen, PfHRP2, with reduced variability.

Paper-based, colorimetric assays have been extensively studied because of their potential for point-of-care diagnostics in resource-limited settings.1–4 In particular, nanomaterials5–8 and enzymes9–11 have been widely employed to associate colorimetric responses with the amounts of analytes in bodily fluids. However, these methods can be subject to low signal-to-noise ratio and time-dependent changes in their visual readouts, which can lead to both false negative and false positive results in the hands of end-users.12–14 To address the need of unambiguous interpretation, polymerization-based signal amplification (PBA) has been explored as alternative chemistry for use in paper-based, colorimetric assays.15 As a biodetection method, it offers rapid response, a high contrast visual signal, and affordability.14,16 PBA employs in situ photoinitiated radical polymerization at a biofunctional interface to quickly generate a biocompatible hydrogel that entraps phenolphthalein, a pH-indicative dye, in the presence of specific binding events (Scheme 1a−c). The amount of the entrapped phenolphthalein is directly related to the amount of polymer and the number of binding events at the interface. Thus, the number of biomolecular


2

Page 3 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


recognition events can be quantified by using the color intensity and size of the hydrogel in alkaline solution, which limits the need for detection equipment. Furthermore, PBA is becoming more cost-effective as low-cost portable light sources are being developed.17 However, there are limitations that can lead to variability when PBA is used in the field. One of the main problems is dye-leaching from the hydrogel, which can cause PBA results to depend on the extent the hydrogel is rinsed. Because the entrapped phenolphthalein can escape the hydrogel, the color of the hydrogel fades when rinsing and storing the hydrogel in alkaline solution before analysis (Scheme 1d). This dye-leaching problem of PBA requires skills to control rinsing and storing conditions, which makes PBA complicated for end-users.

Scheme 1. Polymerization-based signal amplification (PBA) with phenolphthalein or phenolphthalein monomer. a) Eosin Y is concentrated on the paper surface in the presence of target antigen as a result of a paper-based immunoassays.15 b) Monomers and phenolphthalein solution are added to the biofunctional surface and illuminated with green light, producing a


3


Page 4 of 15

phenolphthalein-entrapped hydrogel. c) The excess monomer solution is removed by rinsing, and NaOH solution is added to the hydrogel to make the entrapped phenolphthalein turn pink. d) As the entrapped phenolphthalein diffuses out of the hydrogel, the color of the hydrogel fades. e) Phenolphthalein monomer is used instead of phenolphthalein in b, producing phenolphthaleinconjugated hydrogel. f) The conjugated phenolphthalein turns pink after rinsing the excess monomer solution and adding NaOH solution to the hydrogel. g) The color remains pink because the conjugated phenolphthalein is covalently linked within the hydrogel. Dye-leaching from hydrogels can be prevented by covalently linking the dye molecules to polymers,18,19 reducing the mesh size of hydrogels,20 or increasing the size of dyes.21 However, the latter two methods may not be suitable for PBA because densely crosslinked hydrogel can also inhibit diffusion of alkaline solution into the polymer network, and large dye-loaded particles can non-specifically bind to the biofunctional surface, which will damage PBA’s advantages, such as immediate visualization and high contrast signal, where negative tests remain white. Thus, we used a phenolphthalein monomer in PBA to form a phenolphthalein-conjugated hydrogel to solve the dye-leaching problem of PBA (Scheme 1a, e−g). N-(2-hydroxy-5-(1-(4hydroxyphenyl)-3-oxo-1,3-dihydroisobenzofuran-1-yl)benzyl)acrylamide (1) was selected as the phenolphthalein monomer for two reasons: 1) the amide bond that will connect phenolphthalein and the hydrogel is less reactive in base-catalyzed hydrolysis than the ester bond that will crosslink the polymer22 and 2) the pH-indicative property of 1 can be conserved in copolymers.23,24 Successful copolymerization of 1 with poly(ethylene glycol) diacrylate (PEGDA) and 1-vinyl-2-pyrrolidinone (VP) validated the potential of 1 to solve the dye-leaching problem in PBA. Considering the photoinitiation mechanism of eosin Y and triethanolamine


4

Page 5 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(TEOA), reaction conditions for the modified PBA were determined to achieve the fastest polymerization response. Using the optimized conditions, we tested if the modified PBA can detect malaria antigen, PfHRP2, in the clinically relevant range while reducing the variability in PBA results.

Figure 1. Preparation and characterization of phenolphthalein-conjugated hydrogel (2). A) Reaction scheme for synthesis of 2. B) Evidence for covalently-attached 1 in 2. The initial Oring appeared because the photo was taken before NaOH entirely diffused into hydrogel (Figure S7). C) Conservation of pH-indicative property of 1 in 2. Acronyms : poly(ethylene glycol) diacrylate (PEGDA), 1-vinyl-2-pyrrolidinone (VP), N-(2-hydroxy-5-(1-(4-hydroxyphenyl)-3oxo-1,3-dihydroisobenzofuran-1-yl)benzyl)acrylamide (1), and triethanolamine (TEOA). As a proof of concept experiment, we investigated whether 1 could copolymerize with PEGDA and VP via eosin Y-mediated radical polymerization25–27 while conserving its pH-indicative property. The compound 1 was prepared as described elsewhere,24 characterized (Table S1, Figure S1−S6), and used as a monomer in the radical polymerization with PEGDA and VP to


5


Page 6 of 15

create 2 (Figure 1A). Covalent attachment of 1 to the hydrogel was confirmed by the fact that 1 covalently-emplaced in 2 cannot escape the polymer network in alkaline solution while phenolphthalein entrapped in PEGDA-VP hydrogel can diffuse out of the hydrogel (Figure 1B, S7−S8). Furthermore, the pH-indicative property of 1 was conserved in 2 (Figure 1C). Based on these results, we hypothesized that PBA with a new monomer solution including 1 instead of phenolphthalein could solve the dye-leaching problem of conventional PBA without sacrificing its performance.

Figure 2. Photoinitiation mechanism27 in PBA and reasons for slow PBA response. Since radical polymerization is significantly inhibited by oxygen, PBA response time depends on the rate of photoinitiation, during which oxygen is consumed in photocatalytic cycle. a) Other dyes and aggregates can reduce the light absorption efficiency of eosin Y by absorbing or blocking the same wavelength of light as eosin Y absorbs, which can cause slow photoinitiation. b) Trianion eosin Y radical (EY ∙ ) can be easily protonated in neutral and acidic solution and further reduced to form fully reduced eosin Y (EYH ) via hydrogen abstraction.27 Since it is difficult to


6

Page 7 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


oxidize the fully reduced, colorless form ( EYH ) and regenerate eosin Y

( EY ),27 the

photoinitation becomes slower at lower pH. Prior to testing the hypothesis, we explored the concentrations of 1 and HCl in a phenolphthalein monomer (1)-included monomer solution (PPm solution) and selected the best combination for rapid PBA response, which can allow a limited number of health workers to better attend to many patients. The concentrations of 1 and HCl were chosen as parameters to be optimized because of their impact on the competition between eosin Y and 1 for absorbance of green light and the regeneration yield of eosin Y, which affect the photoinitiation rate and the oxygen inhibition time (Figure 2). For example, if a PPm solution includes too much 1 and too little HCl, the colored form and precipitate of 1 can interfere with the absorption of eosin Y at 490 nm−560 nm, decelerating the photoinitiation in the monomer solution. Besides, too much HCl in PPm solution can also contribute to slow photoinitiation because it prevents regeneration of eosin Y in photocatalytic cycle. Considering both effects, we first minimized the competition between eosin Y and 1 for green light by monitoring UV/Vis spectra of PPm solutions and adjusted the concentration of HCl to obtain optimal conditions that provided the fastest polymerization response (Figure S9). To test if PBA with the optimized PPm solution can detect PfHRP2 at clinically relevant concentrations (~23.5 nM, Figure S13),28,29 we measured the limit of detection (LOD) of the modified PBA and compared with that of PBA with phenolphthalein-included monomer solution (PP solution) (Figure S14). In both cases, hydrogel could be detected with the unaided eye in the presence of 13 nM or more PfHRP2 in 1% PBSA (1% bovine serum albumin in 1×PBS). The calculated LODs of both PBAs were 13 nM, which satisfies the sensitivity requirement for detection of PfHRP2 in the field.


7


Figure

Page 8 of 15

3. Comparison of colorimetric

intensity change over time. The test zone was washed, and fresh 0.01 M NaOH solution was applied at every time point before imaging. A) Representative images of the time course experiment. Noticeable color difference was maintained for an hour between

antigen-negative

and

antigen-

positive samples from PBA with PPm solution. B) Colorimetric intensity (ΔCIE) was obtained by calculating the color difference of each sample from the 60-minute sample produced using PP solution.14 Finally, we performed an experiment to probe whether or not the modified PBA was subject to the dye-leaching problem. We monitored colorimetric intensity of both phenolphthaleinentrapped hydrogel and 2 for an hour (Figure 3). The colorimetric intensity of the hydrogel formed by PBA with PP solution plummets after one additional rinse because the entrapped phenolphthalein can diffuse out of the hydrogel. By contrast, the colorimetric intensity of 2 generated using PPm solution shows only slight decrease after the first additional rinse, and then the intensity remains high enough for people to interpret the test results with the unaided eye. This long-lasting colorimetric signal supports the fact that the conjugated 1 in 2 stays in the polymer network although some entrapped 1 can diffuse out of the hydrogel (Figure S15). It is of note that the colorimetric intensity from PP solution is almost twice as high as one from PPm solution at 0 min. This large difference in colorimetric intensity is attributed to the fact that 1.6


8

Page 9 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


mM phenolphthalein was included in PP solution while only 0.7 mM 1 was dissolved in PPm solution due to lower solubility of 1. In addition, the intensity of 2 for lower concentrations of antigen after repeated rinses was too low to detect antigen even though polymer films were generated (Figure S16). This weakly maintained signals could result from extremely low molar fraction of conjugated 1 in resultant hydrogels created from 0.7 mM 1, 200 mM PEGDA, and 100 mM VP (Figure S16). As shown in Figure 3, we monitored colorimetric intensity of hydrogels in alkaline medium for only an hour. It is not because 2 cannot maintain its color for more than an hour, but because the alkaline solution eventually evaporates. To assess the color retention ability of 2 for a longer time with considering the evaporation of the alkaline medium, we conducted an evaporation-rehydration experiment and confirmed that 1 can stay conjugated to the polymer network of 2 at least for 24 hours (Figure S17). In our study, the phenolphthalein monomer (1) was successfully incorporated into PBA, generating the phenolphthalein-conjugated hydrogel (2) that can maintain its pink color in alkaline medium, including upon drying and rehydration. To achieve this modified PBA, the best reaction conditions were systematically determined considering physicochemical properties of 1 and the photoinitiation mechanism in PBA. However, the low permitted molar fraction of conjugated 1 in hydrogels limited the modified PBA with the reduced variability to detection of 65 nM or more antigen. Since the main reason for this limitation is insolubility of 1 in water, strategies for synthesis of a more water-soluble phenolphthalein monomer are promising future directions to enhance the long-lasting colorimetric intensity by increasing the molar fraction of covalently-attached 1 in hydrogels. We envision that this approach will enable PBA to provide accurate, easy-to-interpret results without difficult operations to control rinsing and storing conditions, improving its user-friendliness, which is an important requirement for adoption.30


9


Page 10 of 15

ASSOCIATED CONTENT Supporting Information. Experimental details, full range of 1D and 2D NMR spectra for phenolphthalein monomer (1), characterization data for phenolphthalein-conjugated hydrogel (2), supplementary data for optimization and assessment of polymerization-based signal amplification with 1. This material is available for free of charge on ACS Publications website.

AUTHOR INFORMATION Corresponding Author *E-mail for H.D.S.: [email protected]. ORCID Hadley D. Sikes: 0000-0002-7096-138X Notes The authors declare that they have no competing interests. Author Contributions The manuscript was written through contributions of both authors. Both authors have given approval to the final version of the manuscript.

ACKNOWLEDGMENTS This research was supported by the Charles E. Reed Faculty Initiatives Fund and the Singapore National Research Foundation under its Antimicrobial Resistance IRG administered by the


10

Page 11 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Singapore-MIT Alliance for Research and Technology. SK acknowledges support from a Gwanjeong Fellowship. The authors thank Emma Yee for her critical reading of the manuscript and Prof. Brad Olsen for helpful discussion.

ABBREVIATIONS PBA, polymerization-based signal amplification; PEGDA, poly(ethylene glycol) diacrylate; VP, 1-vinyl-2-pyrrolidinone; TEOA, triethanolamine; PPm solution, phenolphthalein monomer (1)included monomer solution; PP solution, phenolphthalein-included monomer solution; LOD, limit of detection.

REFERENCES (1)

Martinez, A. W.; Phillips, S. T.; Whitesides, G. M. Diagnostics for the Developing

World: Microfluidic Paper-Based Analytical Devices. Anal. Chem. 2010, 82 (1), 3–10. (2)

Gubala, V.; Harris, L. F.; Ricco, A. J.; Tan, M. X.; Williams, D. E. Point of Care

Diagnostics: Status and Future. Anal. Chem. 2012, 84 (2), 487–515. (3)

Hu, J.; Wang, S.; Wang, L.; Li, F.; Pingguan-Murphy, B.; Lu, T. J.; Xu, F. Advances in

Paper-Based Point-of-Care Diagnostics. Biosens. Bioelectron. 2014, 54, 585–597. (4)

Cate, D. M.; Adkins, J. A.; Mettakoonpitak, J.; Henry, C. S. Recent Developments in

Paper-Based Microfluidic Devices. Anal. Chem. 2015, 87 (1), 19–41.


11


(5)

Page 12 of 15

Liu, J.; Mazumdar, D.; Lu, Y. A Simple and Sensitive “Dipstick” Test in Serum Based on

Lateral Flow Separation of Aptamer-Linked Nanostructures. Angew. Chem. Int. Ed. 2006, 45 (47), 7955–7959. (6)

Ornatska, M.; Sharpe, E.; Andreescu, D.; Andreescu, S. Paper Bioassay Based on Ceria

Nanoparticles as Colorimetric Probes. Anal. Chem. 2011, 83 (11), 4273–4280. (7)

Tsai, T.-T.; Shen, S.-W.; Cheng, C.-M.; Chen, C.-F. Paper-Based Tuberculosis

Diagnostic Devices with Colorimetric Gold Nanoparticles. Sci. Technol. Adv. Mater. 2013, 14 (4). (8)

Chapman, R.; Lin, Y.; Burnapp, M.; Bentham, A.; Hillier, D.; Zabron, A.; Khan, S.;

Tyreman, M.; Stevens, M. M. Multivalent Nanoparticle Networks Enable Point-of-Care Detection of Human Phospholipase-A2 in Serum. ACS Nano 2015, 9 (3), 2565–2573. (9)

Cheng, C.-M.; Martinez, A. W.; Gong, J.; Mace, C. R.; Phillips, S. T.; Carrilho, E.;

Mirica, K. A.; Whitesides, G. M. Paper-Based ELISA. Angew. Chem. Int. Ed. 2010, 49 (28), 4771–4774. (10) Hsu, C.-K.; Huang, H.-Y.; Chen, W.-R.; Nishie, W.; Ujiie, H.; Natsuga, K.; Fan, S.-T.; Wang, H.-K.; Lee, J. Y.-Y.; Tsai, W.-L.; Shimizu, H.; Cheng, C.-M. Paper-Based ELISA for the Detection of Autoimmune Antibodies in Body Fluid-The Case of Bullous Pemphigoid. Anal. Chem. 2014, 86 (9), 4605–4610. (11) Kannan, B.; Jahanshahi-Anbuhi, S.; Pelton, R. H.; Li, Y.; Filipe, C. D. M.; Brennan, J. D. Printed Paper Sensors for Serum Lactate Dehydrogenase Using Pullulan-Based Inks to Immobilize Reagents. Anal. Chem. 2015, 87 (18), 9288–9293.


12

Page 13 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(12) Murdock, R. C.; Shen, L.; Griffin, D. K.; Kelley-Loughnane, N.; Papautsky, I.; Hagen, J. A. Optimization of a Paper-Based ELISA for a Human Performance Biomarker. Anal. Chem. 2013, 85 (23), 11634–11642. (13) Miller, E.; Sikes, H. D. Addressing Barriers to the Development and Adoption of Rapid Diagnostic Tests in Global Health. Nanobiomedicine 2015, 2 (6). (14) Lathwal, S.; Sikes, H. D. Assessment of Colorimetric Amplification Methods in a PaperBased Immunoassay for Diagnosis of Malaria. Lab Chip 2016, 16 (8), 1374–1382. (15) Badu-Tawiah, A. K.; Lathwal, S.; Kaastrup, K.; Al-Sayah, M.; Christodouleas, D. C.; Smith, B. S.; Whitesides, G. M.; Sikes, H. D. Polymerization-Based Signal Amplification for Paper-Based Immunoassays. Lab Chip 2015, 15 (3), 655–659. (16) Kaastrup, K.; Sikes, H. D. Using Photo-Initiated Polymerization Reactions to Detect Molecular Recognition. Chem. Soc. Rev. 2016, 45 (3), 532–545. (17) Dellal, D.; Yee, E.; Lathwal, S.; Sikes, H.; Gomez-Marquez, J. Low-Cost Plug and Play Photochemistry Reactor. HardwareX 2018, 3, 1–9. (18) Liu, L.; Li, X.; Nagao, M.; Elias, A. L.; Narain, R.; Chung, H. J. A pH-Indicating Colorimetric Tough Hydrogel Patch towards Applications in a Substrate for Smart Wound Dressings. Polymers 2017, 9 (11), 558–572. (19) Hah, H. J.; Kim, G.; Lee, Y.-E. K.; Orringer, D. A.; Sagher, O.; Philbert, M. A.; Kopelman, R. Methylene Blue-Conjugated Hydrogel Nanoparticles and Tumor-Cell Targeted Photodynamic Therapy. Macromol. Biosci. 2011, 11 (1), 90–99.


13


Page 14 of 15

(20) Revzin, A.; Russell, R. J.; Yadavalli, V. K.; Koh, W.-G.; Deister, C.; Hile, D. D.; Mellott, M. B.; Pishko, M. V. Fabrication of Poly(Ethylene Glycol) Hydrogel Microstructures Using Photolithography. Langmuir 2001, 17 (18), 5440–5447. (21) Kim, M. D.; Dergunov, S. A.; Lindner, E.; Pinkhassik, E. Dye-Loaded Porous Nanocapsules Immobilized in a Permeable Polyvinyl Alcohol Matrix: A Versatile Optical Sensor Platform. Anal. Chem. 2012, 84 (6), 2695–2701. (22) Mabey, W.; Mill, T. Critical Review of Hydrolysis of Organic Compounds in Water under Environmental Conditions. J. Phys. Chem. Ref. Data 1978, 7 (2), 383–415. (23) Fleischmann, C.; Cheng, J.; Tabatabai, M.; Ritter, H. Extended Applicability of Classical Phenolphthalein: Color Changing Polymeric Materials Derived from pH-Sensitive Acrylated Phenolphthalein Derivatives. Macromolecules 2012, 45 (13), 5343–5346. (24) Fleischmann, C.; Ritter, H. Color Indicator for Supramolecular Polymer Chemistry: Phenolphthalein-Containing Thermo- and pH-Sensitive N-(Isopropyl)Acrylamide Copolymers and β-Cyclodextrin Complexation. Macromol. Rapid Commun. 2013, 34 (13), 1085–1089. (25) Wong, J.; Kaastrup, K.; Aguirre-Soto, A.; Sikes, H. D. A Quantitative Analysis of Peroxy-Mediated Cyclic Regeneration of Eosin under Oxygen-Rich Photopolymerization Conditions. Polymer 2015, 69, 169–177. (26) Kaastrup, K.; Aguirre-Soto, A.; Wang, C.; Bowman, C. N.; Stansbury, J. W.; Sikes, H. D. UV-Vis/FT-NIR in Situ Monitoring of Visible-Light Induced Polymerization of PEGDA Hydrogels Initiated by Eosin/Triethanolamine/O2. Polym. Chem. 2016, 7, 592–602.


14

Page 15 of 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(27) Aguirre-Soto, A.; Kaastrup, K.; Kim, S.; Ugo-Beke, K.; Sikes, H. D. Excitation of Metastable Intermediates in Organic Photoredox Catalysis: Z-Scheme Approach Decreases Catalyst Inactivation. ACS Catal. 2018, 8, 6394-6400. (28) Dondorp, A. M.; Desakorn, V.; Pongtavornpinyo, W.; Sahassananda, D.; Silamut, K.; Chotivanich, K.; Newton, P. N.; Pitisuttithum, P.; Smithyman, A. M.; White, N. J.; Day, N. P. J. Estimation of the Total Parasite Biomass in Acute Falciparum Malaria from Plasma PfHRP2. PLoS Med. 2005, 2 (8), 0788–0797. (29) Manning, L.; Laman, M.; Stanisic, D.; Rosanas-Urgell, A.; Bona, C.; Teine, D.; Siba, P.; Mueller, I.; Davis, T. M. E. Plasma Plasmodium falciparum Histidine-Rich Protein-2 Concentrations Do Not Reflect Severity of Malaria in Papua New Guinean Children. Clin. Infect. Dis. 2011, 52 (4), 440–446. (30) Nilghaz, A.; Guan, L.; Tan, W.; Shen, W. Advances of Paper-Based Microfluidics for Diagnostics - The Original Motivation and Current Status. ACS Sensors 2016, 1 (12), 1382– 1393.

TABLE-OF-CONTENTS / ABSTRACT GRAPHIC


15

Phenolphthalein-Conjugated Hydrogel Formation under Visible-Light

Recommend Documents