This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP (Nos. 2014R1A2A1A01006527 and 2011-0030075).

ייצור 1. של עובש אב המכשיר microfluidic התמקדות הידרודינמית (HFMD) באמצעות ליתוגרפיה <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> עיצוב photomask עבור HFMD (איור 1 א) באמצעות תוכנת מחשב בסיוע עיצוב (CAD) על פי פרוטוקול של היצרן. </li><li style=";text-align:right;direction:rtl"> לשטוף פרוסות סיליקון 4 &#39;עם אצטון, אלכוהול איזופרופיל (IPA), ו ללא יונים (DI) במים כדי להסיר אבק אורגניים ואי-אורגניים מן רקיק. </li><li style=";text-align:right;direction:rtl"> נקו את פרוסות סיליקון עם פלזמה O 2 ב 100 וואט במשך 5 דקות כדי להגביר את כוח מליטה בין רקיק SU-8. </li><li style=";text-align:right;direction:rtl"> ספין-מעיל 4 מ&quot;ל של photoresist שלילית, SU-8 2150, על גבי פרוסות סיליקון בסל&quot;ד 3000 למשך 30 שניות כדי להשיג עובי של 150 מיקרומטר (ב 1 באיור 1b). </li><li style=";text-align:right;direction:rtl"> מניח את הפרוסות מצופות SU-8 על פלטה חמה למשך 5 דקות ב 65 מעלות צלזיוס, להגדיר את הטמפרטורה עד 95 מעלות צלזיוס, ולאחר מכן לעזוב את הרקיק על הפלטה החמה למשך 30 דקות כדי לאפות רך. </li><li style=";text-align:right;direction:rtl"> מניחים אתתוכנן photomask על פרוסות סיליקון ולחשוף לאור UV (260 mJ -2 ס&quot;מ, 26 שניות -2 10 mW ס&quot;מ) aligner המסכה (B2 באיור 1b). </li><li style=";text-align:right;direction:rtl"> בצע שלאחר חשיפה לאפות על פלטה חמה (65 מעלות צלזיוס למשך 5 דקות ולאחר מכן 95 מעלות צלזיוס במשך 12 דקות). </li><li style=";text-align:right;direction:rtl"> פיתוח הרקיק ידי טבילה באמבט מפתח SU-8 למשך 10 דקות, ולאחר מכן להעביר אותו לתוך מפתח טרי במשך 5 שניות כדי לקבל משטח נקי. </li><li style=";text-align:right;direction:rtl"> שוטפים את פרוסות סיליקון עבור 20 שניות עם מים די ולייבשו במשך 10 שניות עם גז N 2 (ב 3 באיור 1b). השתמש רקיק מפוברק כמו עובש אב polydimethylsiloxane (PDMS) הליהוק בסעיף 2. </li></ol> ייצור 2. HFMD דרך יציקת PDMS <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> השתמש רקיק בדוגמת המתקבל בסעיף 1 כמו עובש אמן ליציקת PDMS. </li><li style=";text-align:right;direction:rtl"> מערבבים את מראש פולימר PDMS ואת סוכן ריפוי הומוגנית לפי יחס משקל של 10: 1; למשל, להשתמש 1 גרם של סוכן ריפוי עבור 10 גרם של-polym מראש PDMSאה. </li><li style=";text-align:right;direction:rtl"> יוצקים את PDMS מראש פולימר לתוך התבנית מאסטר ודגה זה עבור שעה 1 בתא ואקום (B4 באיור 1b). </li><li style=";text-align:right;direction:rtl"> מניחים את התבנית הורים עם הקדם-פולימר PDMS לתוך בתנור על 65 מעלות צלזיוס במשך 3 שעות. </li><li style=";text-align:right;direction:rtl"> חותכים את PDMS נרפא לתוך בגודל של שבב יחיד באמצעות אזמל חד. בזהירות לקלף את העתק PDMS נרפא מהתבנית המאסטר ביד. </li><li style=";text-align:right;direction:rtl"> חזור על שלבי 2.2 עד 2.5 עד לקבל העתק PDMS זהה. </li><li style=";text-align:right;direction:rtl"> פונץ כניסה ויציאה חורה לאחת ההעתקים באמצעות-אגרופן חור בקוטר מעט קטן יותר מאשר הקוטר החיצוני של צינורות חיבור. </li><li style=";text-align:right;direction:rtl"> החל טיפול פלזמה אוויר לאזור מליטה של כל העתק באמצעות treater קורונה. 34 זהירות: השתמש treater קורונה באזור עם אוורור טוב כדי למנוע הצטברות אוזון. </li><li style=";text-align:right;direction:rtl"> ירידה של 5 μl של מתנול על אזורי הפלזמה שטופלה האוויר. דק ליישר שני העתקים PDMS זהה לפברק את HFMD ביד manipu<html> אוכלוסייה, ולבדוק יישור באמצעות מיקרוסקופ (B5 באיור 1b). הערה: העתקי PDMS הפלזמה שטופלה האוויר הם די דביקים וקשים לתמרן. לפיכך, 5 μl של מתנול מתווסף אל פני שטח הפלזמה שטופלה האוויר לתפקד כחומר סיכה. </li><li style=";text-align:right;direction:rtl"> מניחים את HFMD בתנור שחומם ל -65 מעלות למשך הלילה C כדי לחזק את הקשר בין שני העתקים PDMS (B6 באיור 1b). בונד שני העתקי PDMS זהים להגדיל את הגובה של microchannel של HFMD ולהימנע סתימת microdroplets בערוץ microfluidic במהלך מבצע. </li></ol><img alt="איור 1" src="/files/ftp_upload/52813/52813fig1.jpg" /> איור 1: סקירה כללית של הליך ייצור HFMD (א) פרמטרים עיצוב של photomask עבור HFMD.. (ב) איור של הליך הייצור עבור HFMD.&quot;Target =&quot; ftp_upload / 52,813 / 52813fig1large.jpg _ blank &quot;&gt; לחץ כאן כדי לצפות בגרסה גדולה יותר של דמות זו. 3. הכנת NIPAAm העשירית (N-עשיר) ו NIPAAm-עלוב (N-עניים) שלבים על ידי הפרדת פאזות של רווית NIPAAm <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> ממיסים מונומר NIPAAm במים DI ב יחס aw / w של 1: 1 בעזרת מערבל מערבולת; למשל, לפזר 10 גרם של NIPAAm ב 10 מ&quot;ל מים DI (התמונה הראשונה של איור 2 א). הערה: לאחר מונומר NIPAAm נמס לגמרי בטמפרטורת חדר, הפתרון נראה עכורה (תמונה שנייה של איור 2 א). תופעה זו היא הסימן הראשון כי הפרדת פאזות מושרה המסיסה של מונומר NIPAAm הרוויה התרחשה בהצלחה. </li><li style=";text-align:right;direction:rtl"> אפשר פתרון מונומר לנוח במצב אנכי בטמפרטורת החדר למשך 15 דקות לפחות. השלב העליון הוא השלב N-העשיר, ואת השלב התחתון הצפוף הוא השלב N-העלוב (תמונה שלישית של איור 2 א). הצפיפויות של הדואר N-עשירים N-עניים שלבים הם 0.93 ± 0.01 ו 0.99 ± 0.01 גרם ס&quot;מ -3, בהתאמה. 15 </li><li style=";text-align:right;direction:rtl"> כאשר ממשק הפרדת שני השלבים מתבהר, לחלץ בזהירות 2 מיליליטר של תמיסת מונומר משלבי N-העשירים N-עניים מבלי להפריע ממשק זה באמצעות פיפטה. </li><li style=";text-align:right;direction:rtl"> הוסף 4 מ&quot;ג של N, -methylenebisacrylamide &#39;N (MBAAm) בתור crosslinker ו -4 מ&quot;ג של 4- (2-hydroxyethoxy) phenyl- (2-הידרוקסי-2-propyl) קטון בתור photoinitiator אל N-עשיר חילוץ N -poor פתרונות מונומר להכין נוזלים הליבה 1 ו -2 לצורך ריכוז crosslinker נמוך (2 מ&quot;ג מ&quot;ל -1) מדגם (B1 ו- B2 באיור 2b). </li><li style=";text-align:right;direction:rtl"> חזור על הצעד קודם 3.3 ולהוסיף 80 מ&quot;ג של MBAAm ו -4 מ&quot;ג של 4- (2-hydroxyethoxy) phenyl- (2-הידרוקסי-2-propyl) קיטון לתוך כל אחד פתרון מונומר חילוץ N-עשיר N-העני להכין נוזלי ליבה 1 ו -2 עבור ריכוז גבוה crosslinker (40 מ&quot;ג מ&quot;ל -1) מדגם (B3 ו- B4 באיוריור 2b). </li><li style=";text-align:right;direction:rtl"> ממיסים 10% WT של פעילי שטח שמן לתוך שמן מינרלי להכין את נוזל נדן (B5 ב איור 2b). </li></ol><img alt="איור 2" src="/files/ftp_upload/52813/52813fig2.jpg" /> איור 2:. הכנת חומר עבור יאנוס Microhydrogel סינתזה (א) הכנת N-עשירים N-עניים פתרונות מונומר באמצעות הפרדת פאזות של NIPAAm רוויה. (ב) פירוט החומרים ההתקנה הניסוי נעשה שימוש בפרוטוקול. <a href="https://www.jove.com/files/ftp_upload/52813/52813fig2large.jpg" target="_blank">אנא לחץ כאן כדי לצפות בגרסה גדולה יותר של דמות זו.</a> סינתזה 4. של יאנוס Microhydrogels שימוש HFMD <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> טען 2 מ&quot;ל של נוזלים הליבה 1 ו -2 (B1, B2 או B3, B4 בתרשים 2b) ואת נוזל נדן (B5 באיור 2b) לשלוש 3 מ&quot;ל מזרקים נפרד. </li&gt; <li style=";text-align:right;direction:rtl"> הר מזרקים לתוך משאבות מזרק ולהתחבר מזרק אחד אל כניסת הנוזל המתאים של HFMD באמצעות צינורות (איור (ב). השתמש צינורות לחיבור לשקע נוזל של HFMD למאגר אוסף. </li><li style=";text-align:right;direction:rtl"> הגדר את משאבות מזרק להשרות נוזלי ליבת 1 ו -2 ו נוזל נדן ברמות ספיקה של 2, 2, ו -10 μl דקות -1, בהתאמה. </li><li style=";text-align:right;direction:rtl"> Tune (אופציונלי) את קצב הזרימה של נוזלים הליבה 1 ו -2 כדי לכוונן את יחסי הנפח היחסי של כל צד של microdroplet יאנוס. </li><li style=";text-align:right;direction:rtl"> מקם את מקור אור UV בניצב על 1 סנטימטר מן המאגר האוסף. הפעילו את מקור האור האולטרה סגול ויזואלית לפקח על ייצור רציף של microhydrogels יאנוס. אזהרה: השימוש UV מגן-משקפים כאשר ניטור ייצור microhydrogel. </li><li style=";text-align:right;direction:rtl"> אסוף את microhydrogels תאנוס מפוברק לתוך צינור חרוטים ולשטוף אותם באמצעות IPA. לאחר מכן, צנטריפוגות צינור חרוטי (780 גרם במשך 5 דק &#39;) כדי ליישב אתmicrohydrogels. </li><li style=";text-align:right;direction:rtl"> חזור על שלב 4.6 כמה פעמים כדי להסיר את שמן מינרלי סביב יאנוס microhydrogels לחלוטין. </li><li style=";text-align:right;direction:rtl"> חזור על שלב מים DI 4.6 אך השימוש עם פעילי שטח המים של 0.005% (v / v) במקום IPA להסיר את IPA שאריות ברחבי microhydrogels יאנוס. </li><li style=";text-align:right;direction:rtl"> אחסן לחלוטין שטף יאנוס microhydrogels בתוך מים די 10 מ&quot;ל בקבוקון המכיל. </li></ol> ניתוח 5.-היענות Thermo אניזוטרופי של יאנוס Microhydrogels <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> השתמש פיפטה למקם יאנוס microhydrogels מסונתז מסעיף 4 לתוך צלחת 24 גם. אפשר microhydrogels להסתפק 15 שניות עד בשכבה נוצר על פני השטח התחתון של הבאר. </li><li style=";text-align:right;direction:rtl"> להשיג תמונה של microhydrogel יאנוס ב 24 ° C באמצעות מיקרוסקופ אופטי זקוף עם עדשה אובייקטיבית 5X. </li><li style=";text-align:right;direction:rtl"> הגדר מודול ותרמית תחת הצלחת היטב ולשלוט מתח של מודול זה כדי להגדיל את הטמפרטורה של תמיסה המכילה מיקרו יאנוסהידרוג ל -32 מעלות צלזיוס. </li><li style=";text-align:right;direction:rtl"> להשיג תמונה של microhydrogel יאנוס על 32 מעלות צלזיוס פעם נוספת באמצעות מיקרוסקופ אופטי זקוף עם עדשה אובייקטיבית 5X. </li><li style=";text-align:right;direction:rtl"> חזור על שלבי 5.2-5.4 24 פעמים, מקפידים לבחור microhydrogel תאנוס שונה לניתוח סטטיסטי. </li><li style=";text-align:right;direction:rtl"> מתוך 25 התמונות של microhydrogels השונה תאנוס ב 24 ו 32 מעלות צלזיוס, למדוד את רדיוס PN-עשיר PN-עניים החלקים microhydrogels יאנוס באמצעות תוכנת ניתוח תמונה על פי הוראות היצרן. </li></ol>

<ol>
	<li>Hoffman, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hydrogels+for+biomedical+applications.">Hydrogels for biomedical applications.</a> Adv. Drug Delivery Rev. 54 (1), 3-12 (2002).</li><li>Qiu, Y., Park, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Environment-sensitive+hydrogels+for+drug+delivery.">Environment-sensitive hydrogels for drug delivery.</a> Adv. Drug Delivery Rev. 53 (3), 321-339 (2001).</li><li>Hirokawa, Y., Tanaka, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volume+phase+transition+in+a+nonionic+gel.">Volume phase transition in a nonionic gel.</a> J. Chem. Phys. 81 (12), 6379-6380 (1984).</li><li>Bae, Y. H., Okano, T., Hsu, R., Kim, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermo-sensitive+polymers+as+on-off+switches+for+drug+release.">Thermo-sensitive polymers as on-off switches for drug release.</a> Macromol. Rapid Commun. 8 (10), 481-485 (1987).</li><li>Yoshida, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comb-type+grafted+hydrogels+with+rapid+deswelling+response+to+temperature+changes.">Comb-type grafted hydrogels with rapid deswelling response to temperature changes.</a> Nature. 374 (6519), 240-242 (1995).</li><li>Tanaka, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Collapse+of+gels+and+the+critical+endpoint.">Collapse of gels and the critical endpoint.</a> Phys. Rev. Lett. 40 (12), 820-823 (1978).</li><li>Tanaka, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+transitions+in+ionic+gels.">Phase transitions in ionic gels.</a> Phys. Rev. Lett. 45 (20), 1636-1639 (1980).</li><li>Zhao, Y. L., Stoddart, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Azobenzene-based+light-responsive+hydrogel+system.">Azobenzene-based light-responsive hydrogel system.</a> Langmuir. 25 (15), 8442-8446 (2009).</li><li>Alvarez-Lorenzo, C., Bromberg, L., Concheiro, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Light-sensitive+intelligent+drug+delivery+systems.">Light-sensitive intelligent drug delivery systems.</a> Photochem. Photobiol. 85 (4), 848-860 (2009).</li><li>Tanaka, T., Nishio, I., Sun, S. T., Ueno-Nishio, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Collapse+of+gels+in+an+electric+field.">Collapse of gels in an electric field.</a> Science. 218 (4571), 467-469 (1982).</li><li>Kwon, I. C., Bae, Y. H., Kim, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrically+credible+polymer+gel+for+controlled+release+of+drugs.">Electrically credible polymer gel for controlled release of drugs.</a> Nature. 354 (6351), 291-293 (1991).</li><li>Obaidat, A. A., Park, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+protein+release+through+glucose-sensitive+hydrogel+membranes.">Characterization of protein release through glucose-sensitive hydrogel membranes.</a> Biomaterials. 18 (11), 801-806 (1997).</li><li>Kataoka, K., Miyazaki, H., Bunya, M., Okano, T., Sakurai, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Totally+synthetic+polymer+gels+responding+to+external+glucose+concentration:+their+preparation+and+application+to+on-off+regulation+of+insulin+release.">Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on-off regulation of insulin release.</a> J. Am. Chem. Soc. 120 (48), 12694-12695 (1998).</li><li>Heskins, M., Guillet, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Solution+properties+of+poly(N-isopropylacrylamide).">Solution properties of poly(N-isopropylacrylamide).</a> J. Macromol. Sci. Part A Pure Appl. Chem. 2 (8), 1441-1455 (1968).</li><li>Sasaki, S., Okabe, S., Miyahara, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermodynamic+properties+of+N-isopropylacrylamide+in+water:+solubility+transition,+phase+separation+of+supersaturated+solution,+and+glass+formation.">Thermodynamic properties of N-isopropylacrylamide in water: solubility transition, phase separation of supersaturated solution, and glass formation.</a> J. Phys. Chem. B. 114 (46), 14995-15002 (2010).</li><li>Bromberg, L., Alakhov, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+polyether-modified+poly(acrylic+acid)+microgels+on+doxorubicin+transport+in+human+intestinal+epithelial+Caco-2+cell+layers.">Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers.</a> J. Controlled Release. 88 (1), 11-22 (2003).</li><li>Coughlan, D. C., Quilty, F. P., Corrigan, O. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+drug+physicochemical+properties+on+swelling/deswelling+kinetics+and+pulsatile+drug+release+from+thermoresponsive+poly(N-isopropylacrylamide)+hydrogels.">Effect of drug physicochemical properties on swelling/deswelling kinetics and pulsatile drug release from thermoresponsive poly(N-isopropylacrylamide) hydrogels.</a> J. Controll. Release. 98 (1), 97-114 (2004).</li><li>Bergbreiter, D. E., Case, B. L., Liu, Y. S., Caraway, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Poly(N-isopropylacrylamide)+soluble+polymer+supports+in+catalysis+and+synthesis.">Poly(N-isopropylacrylamide) soluble polymer supports in catalysis and synthesis.</a> Macromolecules. 31 (18), 6053-6062 (1998).</li><li>Lapeyre, V., Gosse, I., Chevreux, S., Ravaine, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monodispersed+glucose-responsive+microgels+operating+at+physiological+salinity.">Monodispersed glucose-responsive microgels operating at physiological salinity.</a> Biomacromolecules. 7 (12), 3356-3363 (2006).</li><li>Hoare, T., Pelton, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Engineering+glucose+swelling+responses+in+poly(N-isopropylacrylamide)-based+microgels.">Engineering glucose swelling responses in poly(N-isopropylacrylamide)-based microgels.</a> Macromolecules. 40 (3), 670-678 (2007).</li><li>Xu, S., Zhang, J., Paquet, C., Lin, Y., Kumacheva, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+hybrid+microgels+to+photonic+crystals.">From hybrid microgels to photonic crystals.</a> Adv. Funct. Mater. 13 (6), 468-472 (2003).</li><li>Clarke, J., Vincent, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stability+of+non-aqueous+microgel+dispersions+in+the+presence+of+free+polymer.">Stability of non-aqueous microgel dispersions in the presence of free polymer.</a> J. Chem. Soc., Faraday Trans. 1. 77 (8), 1831-1843 (1981).</li><li>Mears, S. J., Deng, Y., Cosgrove, T., Pelton, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Structure+of+sodium+dodecyl+sulfate+bound+to+a+poly+(NIPAM)+microgel+particle.">Structure of sodium dodecyl sulfate bound to a poly (NIPAM) microgel particle.</a> Langmuir. 13 (7), 1901-1906 (1997).</li><li>Shah, R. K., Kim, J. W., Agresti, J. J., Weitz, D. A., Chu, L. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+of+monodisperse+thermosensitive+microgels+and+gel+capsules+in+microfluidic+devices.">Fabrication of monodisperse thermosensitive microgels and gel capsules in microfluidic devices.</a> Soft Matter. 4 (12), 2303-2309 (2008).</li><li>Jack, C. R., Forbes, G., Dewanjee, M. K., Brown, M. L., Earnest, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polyvinyl+alcohol+sponge+for+embolotherapy:+particle+size+and+morphology.">Polyvinyl alcohol sponge for embolotherapy: particle size and morphology.</a> Am. J. Neuroradiol. 6 (4), 595-597 (1985).</li><li>Derdeyn, C. P., Moran, C. J., Cross, D. T., Dietrich, H. H., Dacey, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polyvinyl+alcohol+particle+size+and+suspension+characteristics.">Polyvinyl alcohol particle size and suspension characteristics.</a> Am. J. Neuroradiol. 16 (6), 1335-1343 (1995).</li><li>Han, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+flow+rates+on+generation+of+monodisperse+clay-poly(N-isopropylacrylamide)+embolic+microspheres+using+hydrodynamic+focusing+microfluidic+device.">Effect of flow rates on generation of monodisperse clay-poly(N-isopropylacrylamide) embolic microspheres using hydrodynamic focusing microfluidic device.</a> Jpn. J. Appl. Phys. 50 (6), 06-12 (2011).</li><li>Seo, K. D., Doh, J., Kim, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-step+microfluidic+synthesis+of+Janus+microhydrogels+with+anisotropic+thermo-responsive+behavior+and+organophilic/hydrophilic+loading+capability.">One-step microfluidic synthesis of Janus microhydrogels with anisotropic thermo-responsive behavior and organophilic/hydrophilic loading capability.</a> Langmuir. 29 (49), 15137-15141 (2013).</li><li>Seo, K. D., Kim, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic+synthesis+of+thermo-responsive+poly(N-isopropylacrylamide)-poly(ethylene+glycol)+diacrylate+microhydrogels+as+chemo-embolic+microspheres.">Microfluidic synthesis of thermo-responsive poly(N-isopropylacrylamide)-poly(ethylene glycol) diacrylate microhydrogels as chemo-embolic microspheres.</a> J. Micromech. Microeng. 24 (8), 085001 (2014).</li><li>Seo, K. D., Kwak, B. K., Kim, D. S., S&#225;nchez, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic-assisted+fabrication+of+flexible+and+location+traceable+organo-motor.">Microfluidic-assisted fabrication of flexible and location traceable organo-motor.</a> IEEE Trans. Nanobiosci. 14 (3), 298-304 (2015).</li><li>Seo, K. D., Kim, D. S., S&#225;nchez, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+and+application+of+complex-shaped+microparticles+via+microfluidics.">Fabrication and application of complex-shaped microparticles via microfluidics.</a> Lab Chip. , (2015).</li><li>Shah, R. K., Kim, J. W., Weitz, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Janus+supraparticles+by+induced+phase+separation+of+nanoparticles+in+droplets.">Janus supraparticles by induced phase separation of nanoparticles in droplets.</a> Adv. Mater. 21 (19), 1949-1953 (2009).</li><li>Lone, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic+synthesis+of+Janus+particles+by+UV-directed+phase+separation.">Microfluidic synthesis of Janus particles by UV-directed phase separation.</a> Chem. Commun. 47 (9), 2634-2636 (2011).</li><li>Hauber, K., Drier, T., Beebe, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PDMS+bonding+by+means+of+a+portable,+low-cost+corona+system.">PDMS bonding by means of a portable, low-cost corona system.</a> Lab chip. 6 (12), 1548-1549 (2006).</li><li>Nisisako, T., Torii, T., Takahashi, T., Takizawa, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+monodisperse+bicolored+Janus+particles+with+electrical+anisotropy+using+a+microfluidic+co-flow+system.">Synthesis of monodisperse bicolored Janus particles with electrical anisotropy using a microfluidic co-flow system.</a> Adv. Mater. 18 (9), 1152-1156 (2006).</li><li>Seiffert, S., Romanowsky, M. B., Weitz, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Janus+microgels+produced+from+functional+precursor+polymers.">Janus microgels produced from functional precursor polymers.</a> Langmuir. 26 (18), 14842-14847 (2010).</li><li>Peppas, N. A., Hilt, J. Z., Khademhosseini, A., Langer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hydrogels+in+biology+and+medicine:+from+molecular+principles+to+bionanotechnology.">Hydrogels in biology and medicine: from molecular principles to bionanotechnology.</a> Adv. Mater. 18 (11), 1345-1360 (2006).</li></ol>

The authors declare that they have no competing financial interests.

שני חומרי הבסיס immiscible משמשים בדרך כלל כדי לסנתז את microhydrogels יאנוס. עד לאחרונה, תאנוס microhydrogels המורכב מאותו חומר הבסיס לעתים רחוקות דווח ואת microhydrogels יאנוס הדיווח לא היה מורפולוגיה פנימית ברורה עקב ההפרעה הנגרמת על ידי miscibility של מחומרים המרכיבים. 35, 36 בפרוטוקול זה, ?...

Hydrogels are a network of hydrophilic polymer chains.1 An increasing amount of research in the field of hydrogels has promoted significant advances and revealed their similarity to biological tissues; the properties of hydrogels allow the uptake of large amounts of water while maintaining their structure. Environmentally responsive hydrogels have also been studied extensively because of their ability to swell or shrink reversibly in response to external stimuli.2 Several triggers, including temperature,3-5 pH,6,7 light,8,9 electric fields,10,11 and specific molecules, such as glucose,12,13 have been suggested to control the geometric shape of hydrogels. Among the many environmentally responsive hydrogels currently available, poly(N-isopropylacrylamide) (PNIPAAm), a well-known thermo-responsive hydrogel, exhibits volume shrinkage above a low critical solution temperature (LCST) of 32 &#176;C.14 A recent study by Sasaki et al.15 reported the intriguing liquid-liquid phase separation of supersaturated NIPAAm, which is the monomer of PNIPAAm. According to this report, supersaturated NIPAAm was dissolved with a 10-fold molar excess of H2O, and soon after, the solution separated into two liquid phases when allows to stand at a temperature above 25 &#176;C; by contrast, dilute NIPAAm was dissolved homogeneously under the same conditions.
Microparticles made of environmentally responsive hydrogels are fascinating candidates for application in drug delivery,16,17 catalysis,18 sensing,19,20 and photonics.21 Traditional synthetic methods including emulsion polymerization, are used to produce hydrogel microparticles with polydispersity.22,23 However, certain applications require microparticles with a narrow size distribution, for example, to stabilize the pharmacokinetics of drug delivery.24 Irregularly shaped or polydisperse embolic microparticles aggregate proximally into clusters, leading to chronic inflammatory responses in embolic particles for cancer therapeutic treatment.25,26
The microfluidic approach is at the forefront of research as a means of fabricating micro-sized particles with narrow size distributions and complex shapes.27-31 The advantages of fabricating microparticles in the microfluidic device are predicated by the small characteristic length of the microfluidic device, which results in a low Reynolds number. In contrast to traditional bulk emulsification where drops are formed in parallel, microdroplets produced in microfluidic devices are generated in series and subsequently polymerized into microparticles upon exposure to UV irradiation. The fundamental principle of droplet formation using a microfluidic device is balance between the interfacial tension and the shear force of the sheath fluid acting on the core fluid. 
Despite the obvious advantages of microfluidic fabrication of droplets/particles, Janus droplets/particles consisting of the same base material are rarely reported because the internal morphology of these droplets/particles is generally disturbed by the diffusion and perturbation of the core fluids. To circumvent this intrinsic limitation, two groups recently reported the preparation of the Janus microparticles by employing heat-induced phase separation of colloidal nanoparticles and UV-directed phase separation.32,33
To this end, we report a microfluidic approach to synthesize Janus microhydrogels entirely composed of a single base material and obtain a product with clearly compartmentalized morphology. Our approach is based on the primary concept of liquid-liquid phase separation of supersaturated NIPAAm monomer. The resulting Janus microhydrogels were found to possess unique properties including anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability.

<table border="0" cellpadding="0" cellspacing="0" width="590">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Silicon wafer</td>
			<td style="width:88px;">LG Siltron</td>
			<td style="width:119px;">4&#34;, Test grade</td>
			<td style="width:167px;">Wafer for master mold fabrication</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Acetone</td>
			<td style="width:88px;">Samchun Pure Chemical</td>
			<td style="width:119px;">A0097</td>
			<td>Cleaning silicon wafer</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Isopropyl alcohol (IPA)</td>
			<td style="width:88px;">Daejung Chemicals &#38; Metals</td>
			<td style="width:119px;">5035-4404</td>
			<td>Cleaning silicon wafer</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Water purification system</td>
			<td style="width:88px;">Merck Millipore</td>
			<td style="width:119px;">EMD Millipore RIOs Essential 5</td>
			<td>Prepering&#160; deionized water</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">O2 plasma machine</td>
			<td style="width:88px;">Femto Science</td>
			<td style="width:119px;">VITA-A</td>
			<td>Cleaning silicon wafer</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">SU-8 2150 negative photoresist</td>
			<td style="width:88px;">MicroChem</td>
			<td style="width:119px;">Y111077 0500L1GL</td>
			<td>Photoresist for master mold fabrication</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Hot plate</td>
			<td style="width:88px;">Misung Scientific</td>
			<td style="width:119px;">HP330D, HP150D</td>
			<td>Baking SU-8</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">SU-8 developer</td>
			<td style="width:88px;">Microchem</td>
			<td style="width:119px;">Y020100 4000L1PE</td>
			<td>Developing SU-8</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Mask aligner system for photolithograpy</td>
			<td style="width:88px;">Shinu Mst Co.</td>
			<td style="width:119px;">CA-6M</td>
			<td>Photolithography</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Sylgard 184 silicone elastomer kit</td>
			<td style="width:88px;">Dow Corning</td>
			<td style="width:119px;">1064891</td>
			<td>PDMS casting</td>
		</tr>
		<tr height="80">
			<td height="80" style="height:80px;width:216px;">Laboratory Corona Treater</td>
			<td style="width:88px;">Electro-technic Products Inc.</td>
			<td style="width:119px;">Model BD-20AC</td>
			<td>PDMS air plasma treatment&#160;</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">N-isopropylacrylamide (NIPAAm)</td>
			<td style="width:88px;">Sigma-Aldrich</td>
			<td style="width:119px;">415324-50G</td>
			<td>Monomer</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">N,N&#39;-methylenebisacrylamide (MBAAm)</td>
			<td style="width:88px;">Sigma-Aldrich</td>
			<td style="width:119px;">146072-100G</td>
			<td>Crosslinker of NIPAAm</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone, Irgacure 2959</td>
			<td style="width:88px;">BASF</td>
			<td style="width:119px;">55047962</td>
			<td>Photoinitiator of NIPAAm</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">ABIL EM 90</td>
			<td style="width:88px;">Evonik Industries</td>
			<td style="width:119px;">201109</td>
			<td>Sufactant for oil</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Vortex mixer</td>
			<td style="width:88px;">Scientific Industries Inc.</td>
			<td style="width:119px;">Vortex-Genie 2</td>
			<td>Mixing</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Tygon tubing</td>
			<td style="width:88px;">Saint-Gobain</td>
			<td style="width:119px;">I.D. 1/32&#34;, O.D. 3/32&#34;, Wall 1/32&#34;</td>
			<td>Connecting tube between syringes and HFMD</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">UV light source</td>
			<td style="width:88px;">Hamamatsu</td>
			<td style="width:119px;">Spot light source LC8</td>
			<td>Polymerization from NIPAAm to PNIPAAm</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:216px;">Syringes, NORM-JECT (3ml)</td>
			<td style="width:88px;">Henke-Sass Wolf GmbH</td>
			<td style="width:119px;">22767</td>
			<td>Loading of materials</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Syringe pump</td>
			<td style="width:88px;">KD Scientific</td>
			<td style="width:119px;">KDS model 200</td>
			<td>Perfusion of materials</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Tegitol Type NP-10</td>
			<td style="width:88px;">Sigma-Aldrich</td>
			<td style="width:119px;">NP10-500ML</td>
			<td>Surfactant for water</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Oil red O</td>
			<td style="width:88px;">Sigma-Aldrich</td>
			<td style="width:119px;">O0625-25G</td>
			<td>Dye for N-rich phase</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Oil Blue N</td>
			<td style="width:88px;">Sigma-Aldrich</td>
			<td style="width:119px;">391557-5G</td>
			<td>Dye for N-rich phase</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Yellow food dye</td>
			<td style="width:88px;">Edentown F&#38;B</td>
			<td style="width:119px;">NA</td>
			<td>Dye for N-poor phase</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Green food dye</td>
			<td style="width:88px;">Edentown F&#38;B</td>
			<td style="width:119px;">NA</td>
			<td>Dye for N-poor phase</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Power supply</td>
			<td style="width:88px;">Agilent</td>
			<td style="width:119px;">E3649A</td>
			<td>Power soruce for thermoelectric moduel</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Thermoelectric module</td>
			<td style="width:88px;">Peltier</td>
			<td style="width:119px;">FALC1-12710T125</td>
			<td>Temparature control</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Centrifuge machine</td>
			<td style="width:88px;">Labogene</td>
			<td style="width:119px;">1248R</td>
			<td>Settling down microhydrogels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">24-well plate</td>
			<td style="width:88px;">SPL Life Sciences</td>
			<td style="width:119px;">32024</td>
			<td>Reservoir for observation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Optical microscope</td>
			<td style="width:88px;">Nikon</td>
			<td style="width:119px;">ECLIPSE 80i</td>
			<td>Optical observation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Image analysis software</td>
			<td style="width:88px;">IMT i-Solution Inc.</td>
			<td style="width:119px;">iSolutions DT</td>
			<td>Measurement of radius</td>
		</tr>
	</tbody>
</table>

synthesis of poly(n-isopropylacrylamide) janus microhydrogels for anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability

Janus microparticles are compartmentalized particles with differing molecular structures and/or functionality on each of their two sides. Because of this unique property, Janus microparticles have been recognized as a new class of materials, thereby attracting a great deal of attention from various research fields. The versatility of these microparticles has been exemplified through their uses as building blocks for self-assembly, electrically responsive actuators, emulsifiers for painting and cosmetics, and carriers for drug delivery. This study introduces a detailed protocol that explicitly describes a synthetic method for designing novel Janus microhydrogels composed of a single base material, poly(N-isopropylacrylamide) (PNIPAAm). Janus microdroplets are firstly generated via a hydrodynamic focusing microfluidic device (HFMD) based on the separation of a supersaturated aqueous NIPAAm monomer solution and subsequently polymerized through exposure to UV irradiation. The resulting Janus microhydrogels were found to be entirely composed of the same base material, featured an easily identifiable compartmentalized morphology, and exhibited anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability. We believe that the proposed method introduces a novel hydrogel platform with the potential for advanced synthesis of multi-functional Janus microhydrogels.

איור 3 א מציג סכמטי של הגדרת הניסוי בשימוש לסנתז יאנוס microhydrogels דרך HFMD. N-עשיר שלב N-עניים הוזרקו בדיוק לתוך HFMD כמו נוזלי ליבת 1 ו -2 ולאחר מכן התמזג התפרק microdroplets יאנוס על הפתח ידי נוזל הנדן של שמן מינרלים בגלל חוסר יציבות נימי ריילי. כתוצאה ...

Watch this Scientific Journal Video about Synthesis of PolyN-isopropylacrylamide Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability at JoVE.com

Synthesis of PolyN-isopropylacrylamide Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

We present a protocol to synthesize Janus microhydrogels composed entirely of the same base material, poly(N-isopropylacrylamide) (PNIPAAm), with a clearly compartmentalized structure base on the phase separation of a supersaturated NIPAAm monomer solution. The synthesized Janus microhydrogels show unique properties such as anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability.

סינתזה של פולי (<em&gt; N</em&gt; -isopropylacrylamide) יאנוס Microhydrogels בשל חוסר תגובה Thermo אניזוטרופי ו Organophilic / טוען הידרופיליות יכולת

Janus microparticles are compartmentalized particles with differing molecular structures and/or functionality on each of their two sides. Because of this ...

synthesis-poly-n-isopropylacrylamide-janus-microhydrogels-for

Research

JoVE Journal

Chemistry

Synthesis of Poly(N-isopropylacrylamide) Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

9.9K Views.  Pohang University of Science and Technology (POSTECH). We present a protocol to synthesize Janus microhydrogels composed entirely of the same base material, poly(N-isopropylacrylamide) (PNIPAAm), with a clearly compartmentalized structure base on the phase separation of a supersaturated NIPAAm monomer solution. The synthesized Janus microhydrogels show unique properties such as anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability.

Video: Synthesis of PolyN-isopropylacrylamide Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain.

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

Fluorescence sensors are powerful tools in life science. Here we describe a methodology to synthesize and use dendrimer-based fluorescent sensors to measure pH in living cells and in vivo. The dendritic scaffold enhances the properties of conjugated fluorescent dyes leading to improved sensing properties.

סינתזה, משלוח נייד ו<em&gt; בvivo</em&gt; יישום של חיישני pH מבוססי dendrimer

The development of  fluorescent indicators represented a revolution for life sciences. Genetically  encoded and synthetic fluorophores with sensing ...

Seeded Synthesis of CdSe/CdS Rod and Tetrapod Nanocrystals

We demonstrate a method for the synthesis of multicomponent nanostructures consisting of CdS and CdSe with rod and tetrapod morphologies. A seeded synthesis strategy is used in which spherical seeds of CdSe are prepared first using a hot-injection technique. By controlling the crystal structure of the seed to be either wurtzite or zinc-blende, the subsequent hot-injection growth of CdS off of the seed results in either a rod-shaped or tetrapod-shaped nanocrystal, respectively. The phase and morphology of the synthesized nanocrystals are confirmed using X-ray diffraction and transmission electron microscopy, demonstrating that the nanocrystals are phase-pure and have a consistent morphology. The extinction coefficient and quantum yield of the synthesized nanocrystals are calculated using UV-Vis absorption spectroscopy and photoluminescence spectroscopy. The rods and tetrapods exhibit extinction coefficients and quantum yields that are higher than that of the bare seeds. This synthesis demonstrates the precise arrangement of materials that can be achieved at the nanoscale by using a seeded synthetic approach.

A protocol for the seeded synthesis of rod-shaped and tetrapod-shaped multicomponent nanostructures consisting of CdS and CdSe is presented.

We demonstrate a method for the synthesis of multicomponent nanostructures consisting of CdS and CdSe with rod and tetrapod morphologies. A seeded ...

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zempl&#233;n.

Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme activity monitoring. Especially for glucose type structures previous syntheses proved to be challenging and low yielding. Our novel approach employs indoxylic acid esters as precious intermediates to yield a considerable number of indoxyl glycosides in good yields.

סינתזה של Indoxyl-גליקוזידים לאיתור של פעילויות glycosidase

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

פרוטוקול לסינתזה של<em&gt; Ortho</em&gt; נגזרי אנילין -trifluoromethoxylated

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

סינתזה ואפיון של קולואידים מולקולריים

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

סינתזה של חלבון Bioconjugates<em&gt; דרך</em&gt; כימיה ציסטאין-maleimide

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Hydroquinone Based Synthesis of Gold Nanorods

Gold nanorods are an important kind of nanoparticles characterized by peculiar plasmonic properties. Despite their widespread use in nanotechnology, the synthetic methods for the preparation of gold nanorods are still not fully optimized. In this paper we describe a new, highly efficient, two-step protocol based on the use of hydroquinone as a mild reducing agent. Our approach allows the preparation of nanorods with a good control of size and aspect ratio (AR) simply by varying the amount of hexadecyl trimethylammonium bromide (CTAB) and silver ions (Ag+) present in the "growth solution". By using this method, it is possible to markedly reduce the amount of CTAB, an expensive and cytotoxic reagent, necessary to obtain the elongated shape. Gold nanorods with an aspect ratio of about 3 can be obtained in the presence of just 50 mM of CTAB (versus 100 mM used in the standard protocol based on the use of ascorbic acid), while shorter gold nanorods are obtained using a concentration as low as 10 mM.

This paper describes a protocol for the synthesis of gold nanorods, based on the use of hydroquinone as reducing agent, plus the different mechanisms for controlling their size and aspect ratio.

סינתזה הידרוקינון המבוססת של Nanorods הזהב

Gold nanorods are an important kind of nanoparticles characterized by peculiar plasmonic properties. Despite their widespread use in nanotechnology, the ...

Controlled Synthesis and Fluorescence Tracking of Highly Uniform Poly(N-isopropylacrylamide) Microgels

Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this work, we use single particle tracking of fluorescently labeled PNIPAM microgels as a showcase for tuning microgel size by a rapid non-stirred precipitation polymerization procedure. This approach is well suited for prototyping new reaction compositions and conditions or for applications that do not require large amounts of product. Microgel synthesis, particle size and structure determination by dynamic and static light scattering are detailed in the protocol. It is shown that the addition of functional comonomers can have a large influence on the particle nucleation and structure. Single particle tracking by wide-field fluorescence microscopy allows for an investigation of the diffusion of labeled tracer microgels in a concentrated matrix of non-labeled microgels, a system not easily investigated by other methods such as dynamic light scattering.

Controlled Synthesis and Fluorescence Tracking of Highly Uniform PolyN-isopropylacrylamide Microgels

Non-stirred precipitation polymerization provides a rapid, reproducible prototyping approach to the synthesis of stimuli-sensitive poly(N-isopropylacrylamide) microgels of narrow size distribution. In this protocol synthesis, light scattering characterization and single particle fluorescence tracking of these microgels in a wide-field microscopy setup are demonstrated.

סינתזה מבוקרת מעקב הקרינה של פולי אחיד מאוד (<em&gt; N</em&gt; -isopropylacrylamide) Microgels

Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this ...

Facet-to-facet Linking of Shape-anisotropic Colloidal Cadmium Chalcogenide Nanostructures

Here, we describe a protocol that allows for shape-anisotropic cadmium chalcogenide nanocrystals (NCs), such as nanorods (NRs) and tetrapods (TPs), to be covalently and site-specifically linked via their end facets, resulting in polymer-like linear or branched chains. The linking procedure begins with a cation-exchange process in which the end facets of the cadmium chalcogenide NCs are first converted to silver chalcogenide. This is followed by the selective removal of ligands at their surface. This results in cadmium chalcogenide NCs with highly reactive silver chalcogenide end facets that spontaneously fuse upon contact with each other, thereby establishing an interparticle facet-to-facet attachment. Through the judicious choice of precursor concentrations, an extensive network of linked NCs can be produced. Structural characterization of the linked NCs is carried out via low- and high-resolution transmission electron microscopy (TEM), as well as energy-dispersive X-ray spectroscopy, which confirm the presence of silver chalcogenide domains between chains of cadmium chalcogenide NCs.

A protocol detailing how shape-anisotropic colloidal cadmium chalcogenide nanocrystals can be covalently linked via their end facets is presented here.

פן-כדי-היבט הקישור של קדמיום Colloidal צורה-אניסוטרופי Chalcogenide Nanostructures

Here, we describe a protocol that allows for shape-anisotropic cadmium chalcogenide nanocrystals (NCs), such as nanorods (NRs) and tetrapods (TPs), to be ...

Grafting Multiwalled Carbon Nanotubes with Polystyrene to Enable Self-Assembly and Anisotropic Patchiness

We demonstrate a straightforward protocol to graft pristine multiwalled carbon nanotubes (MWCNTs) with polystyrene (PS) chains at the sidewalls through a free-radical polymerization strategy to enable the modulation of the nanotube surface properties and produce supramolecular self-assembly of the nanostructures. First, a selective hydroxylation of the pristine nanotubes through a biphasic catalytically mediated oxidation reaction creates superficially distributed reactive sites at the sidewalls. The latter reactive sites are subsequently modified with methacrylic moieties using a silylated methacrylic precursor to create polymerizable sites. Those polymerizable groups can address further polymerization of styrene to produce a hybrid nanomaterial containing PS chains grafted to the nanotube sidewalls. The polymer-graft content, amount of silylated methacrylic moieties introduced and hydroxylation modification of the nanotubes are identified and quantified by Thermogravimetric Analysis (TGA). The presence of reactive functional groups hydroxyl and silylated methacrylate are confirmed by Fourier Transform Infrared Spectroscopy (FT-IR). Polystyrene-grafted carbon nanotube solutions in tetrahydrofuran (THF) provide wall-to-wall collinearly self-assembled nanotubes when cast samples are analyzed by transmission electron microscopy (TEM). Those self-assemblies are not obtained when suitable blanks are similarly cast from analogous solutions containing non-grafted counterparts. Therefore, this method enables the modification of the nanotube anisotropic patchiness at the sidewalls which results into spontaneous auto-organization at the nanoscale.

A procedure for the synthesis of polystyrene-grafted multiwalled carbon nanotubes using successive chemical modification steps to selectively introduce the polymer chains to the sidewalls and their self-assembly via anisotropic patchiness is presented.

הרכבה Multiwalled פחמן עם פוליסטירן כדי לאפשר הרכבה עצמית, Patchiness אנאיזוטרופי

We demonstrate a straightforward protocol to graft pristine multiwalled carbon nanotubes (MWCNTs) with polystyrene (PS) chains at the sidewalls through a ...

סינתזה של פולי (

Summary

Explore More Videos

Chapters in this video

סינתזה, משלוח נייד ו

Seeded Synthesis of CdSe/CdS Rod and Tetrapod Nanocrystals

סינתזה של Indoxyl-גליקוזידים לאיתור של פעילויות glycosidase

פרוטוקול לסינתזה של

סינתזה ואפיון של קולואידים מולקולריים

סינתזה של חלבון Bioconjugates

סינתזה הידרוקינון המבוססת של Nanorods הזהב

סינתזה מבוקרת מעקב הקרינה של פולי אחיד מאוד (

פן-כדי-היבט הקישור של קדמיום Colloidal צורה-אניסוטרופי Chalcogenide Nanostructures

הרכבה Multiwalled פחמן עם פוליסטירן כדי לאפשר הרכבה עצמית, Patchiness אנאיזוטרופי