החוקרים מכירים בפרס ONR-Muri (NN00014-06-1-1176) והצבא האמריקאי למחקר הרפואי וציוד הפיקוד (גרנט מס W81XWH-10-1-0806) לתמיכה כספית. חומר זה מבוסס על העבודה הנתמכת על ידי הקרן הלאומי למדע תחת גרנט המספר 0552584 EEC ו0851519.

1. סינתזה קומבינטורית פולימר הספרייה (משתנה בכימיה של פולימרים) - ראה איור 1 להגדרת רובוטית <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> ממס מונומר אחד ב( הריכוז = 25 מ&quot;ג / מ&quot;ל) הממס המתאים ולטעון בכל לתוך מזרק גז הדוק 10cc. </li><li style=";text-align:right;direction:rtl"> חבר את צינורות הממס עמיד לפתות נעילת נימים לסוף כל מזרק. </li><li style=";text-align:right;direction:rtl"> הנח את המזרקים על משאבות המזרק (משאבות מזרק לתכנות חדשות Era) ולנעול למקומו. </li><li style=";text-align:right;direction:rtl"> הגדר את המפעילים ליניארי (Zaber) למצב ההתחלתי. </li><li style=";text-align:right;direction:rtl"> באמצעות מהדק מעמד טבעת, למקם את סוף שני צינורות נימים לתוך הבקבוקון מתחיל / גם בתצהיר מונומר. </li><li style=";text-align:right;direction:rtl"> ליזום תכנית LabVIEW, שמשאבות נפחים משתנים של מונומר אחד לכל באר בהתאם להרכב קופולימר הרצוי. זו מושגת בתכנית על ידי מורה למפעיל Z-הציר להנמיך את צינורות נימים לתוך הבקבוקון / גם ואז כל משאבה לוותר עצמה הרצויה. NeXT, התכנית מורה Z-המפעיל לחזור לעמדה שלו ואת בית ה-X ו-Y-המפעילים לעבור לעמדתו של הבקבוקון הבא / כן. זה מתבצע עד שכל אחד יש גם את הנפח הרצוי של מונומר הופקד לתוכו. </li><li style=";text-align:right;direction:rtl"> בעקבות תצהיר מונומר, ספריית מונומר רב היטב או בקבוקון רב מועברת לתנור מחומם מראש ואקום וטופחה תחת ואקום למשך תגובת פילמור העיבוי. לCPH: סינתזת SA התגובה מתבצעת ב 180 מעלות צלזיוס, 0.3 Torr, עבור 1.5 שעות אבל תנאי תגובה אלה ינועו בין מערכות פולימרים שונות. </li></ol> 2. בלנק קומבינטורית וNanoparticle חלבון טעון פולימרים וייצור ספריית סרטים - ראו איור 1 להגדרת רובוטית <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> המזרק במשאבת המזרק לתכנות הראשון מלא ממס (ספרייה ריקה) או ממס עם חלבון מפוזר בזה (ספריית חלבון טעון) ואילו את המזרק במזרק השנימשאבה נשארה ריקה. צינורות לייצור nanoparticle בבעל המדגם הסמוך מתמלאים בהלא ממס (יחס של ממס להלא ממס הוא 1 ל 100). עבור ייצור סרט צלחת ריקה רבה מנוצלת היטב במקומם של הצינורות בבעל המדגם הסמוך. </li><li style=";text-align:right;direction:rtl"> באמצעות תוכנת LabVIEW, הממס מופקד לכל בקבוקוני הפולימר / בארות של הספרייה (ריכוז = 20 מ&quot;ג / מ&quot;ל) וטופח ל1-5 דקות. צעד sonication אופציונלי (30 של ב 40 הרץ) יכול להיות הציג על מנת להבטיח פירוק פולימר שלם. </li><li style=";text-align:right;direction:rtl"> בשלב בא, על ידי ייזום תכנית LabVIEW נפרדת, המדגם נסוג לתוך המזרק הריק, ויופקד בצינור המקביל שלה היטב שאינם ממס-(חלקיקים) או ריק (סרטים) בבעל המדגם הסמוך. </li><li style=";text-align:right;direction:rtl"> תהליך זה מתבצע עבור כל רכב פולימר הספרייה הדיסקרטית. </li><li style=";text-align:right;direction:rtl"> Nanoparticle או ספריית סרטים הועבר אז בתא ואקום להסרת ממס ואינו ממס (מאזני nanoparticleר&quot;י גם ניתן לשחזר באמצעות סינון ואקום). </li></ol> 3. קינטיקס שחרור חלבון תפוקה גבוהה <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> לחקירת קינטיקה שחרור חלבון תפוקה גבוהה מספריית פולימר, 96 עמוקים גאו (2 מ&quot;ל / היטב), צלחת פוליפרופילן היא לשנות כך את ראש 1/3 מהקיר גם בטורים שכנים (לשעבר: A ו-B, C ו-D, E, F, G, H) יוסרה לצרף את הבארות. סרטי חלבון הטעונים חייבים להיות מפוברקים באו החלקיקים הועברו לצלחת זה לביצוע מחקרי קינטיקה שחרור תפוקה גבוהה. דגימות nanoparticle חלבון טעון או סרט חייבות להיות ממוקמות רק בבאר אחת מהעמודות הצמודות (לשעבר: A, C, E, ו-G). ראה תרשים 4 לפרטים. </li><li style=";text-align:right;direction:rtl"> בעקבות ההעברה של החלקיקים לצלחת שחרורו עמוק נקוותה 96, החלקיקים הרשו להם להתיישב. PBS חיץ (0.1 מ&quot;מ, pH 7.4) הוא הוסיף באיטיות לכל דגימה היטב (עמודות A, C, E ו-G) ולאחר מכן לכל השכן היטב (עמודות B, D, F, ו-H) עד הבארות מלאות והחיץ הוא זורם חופשי בין בארות סמוכות. עבור חלקיקים, תהליך זה צריך להתבצע בזהירות נוספת על מנת להבטיח את החלקיקים יישארו בתחתית גם הדגימה (עמודות, C, E ו-G) ואינו מועבר לשחרור הסמוך היטב (עמודות B, D, F , ו-H). במקרים מסוימים, צנטריפוגה נדרשה למקם את דגימות nanoparticle בתחתית הדגימה היטב (עמודות A, C, E ו-G). </li><li style=";text-align:right;direction:rtl"> בשלב הבא, את צלחת שחרורו היא חתום עם מכסה והניחה בטמפרטורה הרצויה (כלומר 37 מעלות צלזיוס) מתחת לתסיסה לתקופת הניסוי. </li><li style=";text-align:right;direction:rtl"> בנקודתי זמן מצטברות (כלומר 0.04, 1, 2, 3, 5, 7, 9, 12, 15, 19, 24, ו 30 ימים) כמות החלבון fluorochrome מצומדות פרסם היא לכמת באמצעות סורק 9400 טיפון משטח פלורסנט ( GE Healthcare). צלחת שחרורו מונחת על משטח הסורק, שנסרק באמצעות ליזר העירור המתאים ופליטת filteRS, ועוצמת הקרינה של החלבון שוחרר בשחרור הבארות (עמודות B, D, F ו-H) הוא לכמת (קוואנט תמונה). הוא הציע כי סטנדרטים של ריכוזי חלבון ידוע להיכלל בצלחת גם לחישוב כמות חלבון וחשבונאי למרווית fluorochrome. </li></ol> 4. נציג תוצאות עם הייצור של פולימר הספרייה, אפיון בוצע עם H NMR 1, GPC, וכדי לאמת את שיטת FTIR קומבינטורית זה 1,7,8,11. טווח משקלים מולקולרי מ10,000-20,000 ג&#39;/ mol, מדד נע polydispersity 1.5-3.0, והרכב כימי הוכח כמדויק ובהסכם עם שיטות קונבנציונליות של סינתזת polyanhydride 12-15. כמו כן, תמונות SEM של ספריות חלקיקים הראו מורפולוגיה דומה לפני שטח, גודל והתפלגות גודל כמו זה של חלקיקים מפוברקים קונבנציונלי 2. חלבון השחרור kinetics מחלקיקי polyanhydride או סרטים מתבצע בצלחת גם שונה כפי שתואר לעיל 1. התוצאות הראה שחרור כדי לאפס משוער עם או בלי פרץ תלוי העמסת חלבון וכימית פולימר (איורים 2 ו -3) 1,12,14,16. <img alt="איור 1" src="/files/ftp_upload/3882/3882fig1.jpg" /> איור 1. סרט קומבינטורית פולימר ומנגנון הייצור nanoparticle. <img alt="איור 2" src="/files/ftp_upload/3882/3882fig2.jpg" /> איור 2 שחרור תפוקה גבוהה של טקסס האדומה השור אלבומין (TRBSA) מCPH:. ספריית פולימר nanoparticle SA. chemistries הפולימר SA-עשיר לשחרר מארז TRBSA במהירות הרבה ביותר, ואילו chemistries הפולימר CPH העשיר לשחרר האיטי ביותר. ברי שגיאה מייצגים סטנדרטית לסטייהtion וn = 4. הודפס מחדש באישור מפטרסן et. אל. 1. כל זכויות שמורה 2010 אגודה אמריקנית לכימיה. <img alt="איור 3" src="/files/ftp_upload/3882/3882fig3.jpg" /> איור 3 לשחרר תפוקה גבוהה של טקסס האדומה השור אלבומין (TRBSA) מCPTEG:. ספריית סרטי פולימר CPH. chemistries הפולימר CPTEG העשיר לשחרר מארז TRBSA במהירות הרבה ביותר, ואילו chemistries הפולימר CPH העשיר לשחרר האיטי ביותר. ברי שגיאה מייצגים סטיית תקן וn = 3. <img alt="איור 4" src="/files/ftp_upload/3882/3882fig4.jpg" /> איור 4. תמונה שמציגה שתי בארות שכנות &quot;לפני&quot; ושינוי &quot;אחרי&quot; בצלחת עמוקה פוליפרופילן גאה 96. התמונה &quot;אחרי&quot; השינוי בימין גם מתארת ​​את התוספת של סרט פולימר (חלק תחתון של שמאל גם) עם מולקולת ניאון כמוסהששוחרר בין שתי בארות לפתרון חיץ. אז מולקולת הניאון שוחרר הוא זוהה בימין גם.

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אין ניגודי האינטרסים הכריזו.

ידע של תנאי הסינתזה הדרושות ואת טמפרטורות מעבר הזכוכית (T g ים) של הפולימרים המסונתזים חיוני לייצור ספרייה. אם T g שלהם מתחת לטמפרטורת חדר, צעד ייצור nanoparticle ייתכן שיצטרך להתבצע בסביבה מבוקרת טמפרטורה מתחת T g של הפולימרים. בנוסף, זהירות יש לנקוט על מנת ל?...

<table border="1" style=";text-align:right;direction:rtl"><tbody><tr><td> שם </td><td> חברה </td><td> מספר קטלוגים </td></tr><tr><td> שלב ממונע XYZ: 3x T-LSM050A, נסיעות 50 מ&quot;מ בציר </td><td> טכנולוגיות Zaber </td><td> T-XYZ-LSM050A-KT04 </td></tr><tr><td> משאבת מזרק יחידה NE-1000 </td><td> מערכות משאבת עידן חדשות </td><td> NE-1000 </td></tr><tr><td> פיירקס * Vista * צינורות תרבות מוקדיות שימוש חוזרים זכוכית </td><td> קורנינג </td><td> 07-250-125 </td></tr><tr><td> cuvettes זכוכית </td><td> אסטרטגיות מדעיות </td><td> G102 </td></tr><tr><td> LabVIEW </td><td> מכשירים הלאומיים </td><td> 776671-35 </td></tr><tr><td> מזרקי SGE גז הדוקים, luer Loc </td><td> סיגמה אולדריץ </td><td> 509507 </td></tr><tr><td> U96 DeepWell צלחות 1.3 מ&quot;ל ו2.0 מ&quot;ל </td><td> Thermo Scientific: Nunc </td><td> 278743 </td></tr><tr><td> גם מחצלות כובע </td><td> Thermo Scientific: Nunc </td><td> 276000 </td></tr><tr><td> טיפון 9400 </td><td> GE Healthcare </td><td> 63-0055-79 </td></tr><tr><td> Whatman כיתת 50 מעגלים 90 מ&quot;מ </td><td> Whatman </td><td> 1450-090 </td></tr></tbody></table>

combinatorial synthesis of and high-throughput protein release from polymer film and nanoparticle libraries

Polyanhydrides הוא קבוצה של חומרים ביולוגיים עם biocompatibility מצוין ויכולות אספקת סמים. בזמן שהם נחקרו רבים עם קונבנציונלי אחד מדגם ב-A-זמן טכניקות סינתזה, גישה אחרונה יותר תפוקה גבוהה פותחה מאפשרת סינתזה והבדיקה של ספריות גדולות של 1 polyanhydrides. זה יאפשר ביצוע אופטימיזציה יעילה יותר ותהליך עיצוב של biomaterials אלה עבור יישומי משלוח סמים וחיסון. שיטת עבודה זו מתארת ​​את הסינתזה קומבינטורית של סרט polyanhydride מתכלה וספריות nanoparticle וזיהוי התפוקה גבוהה של שחרור חלבון מהספריות הללו. בשיטת רובוט מופעל זה (איור 1), ומפעיל ליניארי ומשאבות מזרק נשלטים על ידי LabVIEW, המאפשר פרוטוקול אוטומטי ללא ידות, ביטול שגיאות משתמש. יתר על כן, שיטה זו מאפשרת ייצור המהיר של ספריות פולימר מייקרו בקנה מידה, אדוםucing הגודל יצווה תוך כתוצאה מהיצירה של מערכות פולימרי multivariant. גישה זו לסינתזה קומבינטורית פולימר מאפשרת סינתזה של עד 15 פולימרים שונים בסכום שווה ערך של זמן זה ייקח לסנתז פולימר 1 כמקובל. בנוסף, ספריית פולימר קומבינטורית יכולה להיות מפוברקת בגיאומטריות ריקות או חלבון טעונים כוללים סרטים או חלקיקים עם פיזורה של ספריית הפולימר בממס ומשקעים אל הלא ממס (עבור חלקיקים) או על ידי ייבוש ואקום (לסרטים). בעקבות טעינת חלבון fluorochrome מצומדות לספריות הפולימר, קינטיקה שחרור החלבון ניתן להעריך בתפוקה גבוהה באמצעות שיטת זיהוי מבוססת פלואורסצנטי (איורים 2 ו 3) כפי שתואר לעיל 1. פלטפורמת קומבינטורית זו אומתה בשיטות קונבנציונליות 2 וסרט polyanhydride וספריות nanoparticle התאפיינו עם <sup&gt; 1 H NMR ו FTIR. הספריות נבדקו עבור קינטיקה חלבון שחרור, יציבות וantigenicity; ברעילות סלולרית מבחנה, ציטוקינים ייצור, משטח סמן ביטוי, הדבקה, הפצה ובידול, ובbiodistribution וmucoadhesion 1-11 vivo. השיטה פותחה קומבינטורית להלן מאפשרת סינתזת תפוקה גבוהה פולימר וייצור של חלבון nanoparticle הטעון וספריות סרטים, שיכול, בתורו, להיות מוקרן במבחנת in vivo לאופטימיזציה של ביצועים ביולוגיים.

Watch this Scientific Journal Video about Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries at JoVE.com

Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries

שיטה זו מתארת ​​את הסינתזה קומבינטורית של סרט polyanhydride מתכלה וספריות nanoparticle וזיהוי התפוקה גבוהה של שחרור חלבון מהספריות הללו.

סינתזה קומבינטורית של שחרור חלבון ותפוקה גבוהה מסרט הפולימר וספריות Nanoparticle

Polyanhydrides are a class of biomaterials with excellent biocompatibility and drug delivery capabilities. While they have been studied extensively with ...

combinatorial-synthesis-high-throughput-protein-release-from-polymer

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Bioengineering

10.3K Views.  Iowa State University. שיטה זו מתארת ​​את הסינתזה קומבינטורית של סרט polyanhydride מתכלה וספריות nanoparticle וזיהוי התפוקה גבוהה של שחרור חלבון מהספריות הללו.

Video: Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries

Synthesis, Assembly, and Characterization of Monolayer Protected Gold Nanoparticle Films for Protein Monolayer Electrochemistry

Colloidal gold nanoparticles protected with alkanethiolate ligands called monolayer protected gold clusters (MPCs) are synthesized and subsequently incorporated into film assemblies that serve as adsorption platforms for protein monolayer electrochemistry (PME). PME is utilized as the model system for studying electrochemical properties of redox proteins by confining them to an adsorption platform at a modified electrode, which also serves as a redox partner for electron transfer (ET) reactions. Studies have shown that gold nanoparticle film assemblies of this nature provide for a more homogeneous protein adsorption environment and promote ET without distance dependence compared to the more traditional systems modified with alkanethiol self-assembled monolayers (SAM).1-3 In this paper, MPCs functionalized with hexanethiolate ligands are synthesized using a modified Brust reaction4 and characterized with ultraviolet visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), and proton (1H) nuclear magnetic resonance (NMR). MPC films are assembled on SAM modified gold electrode interfaces by using a "dip cycle" method of alternating MPC layers and dithiol linking molecules. Film growth at gold electrode is tracked electrochemically by measuring changes to the double layer charging current of the system. Analogous films assembled on silane modified glass slides allow for optical monitoring of film growth and cross-sectional TEM analysis provides an estimated film thickness. During film assembly, manipulation of the MPC ligand protection as well as the interparticle linkage mechanism allow for networked films, that are readily adaptable, to interface with redox protein having different adsorption mechanism. For example, Pseudomonas aeruginosa azurin (AZ) can be adsorbed hydrophobically to dithiol-linked films of hexanethiolate MPCs and cytochrome c (cyt c) can be immobilized electrostatically at a carboxylic acid modified MPC interfacial layer. In this report, we focus on the film protocol for the AZ system exclusively. Investigations involving the adsorption of proteins on MPC modified synthetic platforms could further the understanding of interactions between biomolecules and man-made materials, and consequently aid the development of biosensor schemes, ET modeling systems, and synthetic biocompatible materials.5-8

Alkanethiolate stabilized gold colloids known as monolayer protected clusters (MPCs) are synthesized, characterized, and assembled into thin films as an adsorption interface for protein monolayer electrochemistry of simple redox protein like Pseudomonas aeruginosa azurin (AZ) and cytochrome c (cyt c).

סינתזה, הרכבה, אפיון monolayer מוגן סרטים Nanoparticle זהב עבור אלקטרוכימיה monolayer חלבון

Colloidal gold nanoparticles protected with alkanethiolate ligands called monolayer protected gold clusters (MPCs) are synthesized and subsequently ...

A Chitosan Based, Laser Activated Thin Film Surgical Adhesive, 'SurgiLux': Preparation and Demonstration

Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures can act as a nidus for infection and in many procedures are unable to effect wound repair or interfere with functional tissue regeneration.1 Surgical glues and adhesives, such as those based on fibrin and cyanoacrylates, have been developed as alternatives to sutures for the repair of such wounds. However, current commercial adhesives also have significant disadvantages, ranging from viral and prion transfer and a lack of repair strength as with the fibrin glues, to tissue toxicity and a lack of biocompatibility for the cyanoacrylate based adhesives. Furthermore, currently available surgical adhesives tend to be gel-based and can have extended curing times which limit their application.2 Similarly, the use of UV lasers to facilitate cross-linking mechanisms in protein-based or albumin 'solders' can lead to DNA damage while laser tissue welding (LTW) predisposes thermal damage to tissues.3 Despite their disadvantages, adhesives and LTW have captured approximately 30% of the wound closure market reported to be in excess of US $5 billion per annum, a significant testament to the need for sutureless technology.4
In the pursuit of sutureless technology we have utilized chitosan as a biomaterial for the development of a flexible, thin film, laser-activated surgical adhesive termed 'SurgiLux'. This novel bioadhesive uses a unique combination of biomaterials and photonics that are FDA approved and successfully used in a variety of biomedical applications and products. SurgiLux overcomes all the disadvantages associated with sutures and current surgical adhesives (see Table 1).
In this presentation we report the relatively simple protocol for the fabrication of SurgiLux and demonstrate its laser activation and tissue weld strength. SurgiLux films adhere to collagenous tissue without chemical modification such as cross-linking and through irradiation using a comparatively low-powered (120 mW) infrared laser instead of UV light. Chitosan films have a natural but weak adhesive attraction to collagen (~3 KPa), laser activation of the chitosan based SurgiLux films emphasizes the strength of this adhesion through polymer chain interactions as a consequence of transient thermal expansion.5 Without this 'activation' process, SurgiLux films are readily removed.6-9 SurgiLux has been tested both in vitro and in vivo on a variety of tissues including nerve, intestine, dura mater and cornea. In all cases it demonstrated good biocompatibility and negligible thermal damage as a consequence of irradiation.6-10

A Chitosan Based, Laser Activated Thin Film Surgical Adhesive, &#039;SurgiLux&#039;: Preparation and Demonstration

The fabrication of a novel, flexible thin film surgical adhesive from FDA approved ingredients, chitosan and indocyanine green is described. Bonding of this adhesive to collagenous tissue through a simple activation process with a low-powered infra-red laser is demonstrated.

Chitosan מבוסס, דבק הליזר הופעל סרט דק כירורגים, &#39;SurgiLux&#39;: הכנה והפגנה

Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures ...

Polymer Microarrays for High Throughput Discovery of Biomaterials

The discovery of novel biomaterials that are optimized for a specific biological application is readily achieved using polymer microarrays, which allows a combinatorial library of materials to be screened in a parallel, high throughput format1. Herein is described the formation and characterization of a polymer microarray using an on-chip photopolymerization technique 2. This involves mixing monomers at varied ratios to produce a library of monomer solutions, transferring the solution to a glass slide format using a robotic printing device and curing with UV irradiation. This format is readily amenable to many biological assays, including stem cell attachment and proliferation, cell sorting and low bacterial adhesion, allowing the ready identification of 'hit' materials that fulfill a specific biological criterion3-5. Furthermore, the use of high throughput surface characterization (HTSC) allows the biological performance to be correlated with physio-chemical properties, hence elucidating the biological-material interaction6. HTSC makes use of water contact angle (WCA) measurements, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In particular, ToF-SIMS provides a chemically rich analysis of the sample that can be used to correlate the cell response with a molecular moiety. In some cases, the biological performance can be predicted from the ToF-SIMS spectra, demonstrating the chemical dependence of a biological-material interaction, and informing the development of hit materials5,3.

A description of the formation of a polymer microarray using an on-chip photopolymerization technique. The high throughput surface characterization using atomic force microscopy, water contact angle measurements, X-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry and a cell attachment assay is also described.

Microarrays פולימר לגילוי תפוקה גבוהה של Biomaterials

The discovery of novel biomaterials that are optimized for a specific biological application is readily achieved using polymer microarrays, which allows a ...

High-throughput Protein Expression Generator Using a Microfluidic Platform

Rapidly increasing fields, such as systems biology, require the development and implementation of new technologies, enabling high-throughput and high-fidelity measurements of large systems. Microfluidics promises to fulfill many of these requirements, such as performing high-throughput screening experiments on-chip, encompassing biochemical, biophysical, and cell-based assays1. Since the early days of microfluidics devices, this field has drastically evolved, leading to the development of microfluidic large-scale integration2,3. This technology allows for the integration of thousands of micromechanical valves on a single device with a postage-sized footprint (Figure 1). We have developed a high-throughput microfluidic platform for generating in vitro expression of protein arrays (Figure 2) named PING (Protein Interaction Network Generator). These arrays can serve as a template for many experiments such as protein-protein 4, protein-RNA5 or protein-DNA6 interactions.
The device consist of thousands of reaction chambers, which are individually programmed using a microarrayer. Aligning of these printed microarrays to microfluidics devices programs each chamber with a single spot eliminating potential contamination or cross-reactivity Moreover, generating microarrays using standard microarray spotting techniques is also very modular, allowing for the arraying of proteins7, DNA8, small molecules, and even colloidal suspensions. The potential impact of microfluidics on biological sciences is significant. A number of microfluidics based assays have already provided novel insights into the structure and function of biological systems, and the field of microfluidics will continue to impact biology.

We present a microfluidic approach for the expression of protein arrays. The device consists of thousands of reaction chambers controlled by micro-mechanical valves. The microfluidic device is mated to a microarray-printed gene library. These genes are then transcribed and translated on-chip, resulting in a protein array ready for experimental use.

גנרטור ביטוי חלבון תפוקה גבוהה באמצעות פלטפורמת Microfluidic

Rapidly increasing fields, such as systems biology, require the development and implementation of new technologies, enabling high-throughput and ...

High-throughput Synthesis of Carbohydrates and Functionalization of Polyanhydride Nanoparticles

Transdisciplinary approaches involving areas such as material design, nanotechnology, chemistry, and immunology have to be utilized to rationally design efficacious vaccines carriers. Nanoparticle-based platforms can prolong the persistence of vaccine antigens, which could improve vaccine immunogenicity1. Several biodegradable polymers have been studied as vaccine delivery vehicles1; in particular, polyanhydride particles have demonstrated the ability to provide sustained release of stable protein antigens and to activate antigen presenting cells and modulate immune responses2-12.
The molecular design of these vaccine carriers needs to integrate the rational selection of polymer properties as well as the incorporation of appropriate targeting agents. High throughput automated fabrication of targeting ligands and functionalized particles is a powerful tool that will enhance the ability to study a wide range of properties and will lead to the design of reproducible vaccine delivery devices.
The addition of targeting ligands capable of being recognized by specific receptors on immune cells has been shown to modulate and tailor immune responses10,11,13 C-type lectin receptors (CLRs) are pattern recognition receptors (PRRs) that recognize carbohydrates present on the surface of pathogens. The stimulation of immune cells via CLRs allows for enhanced internalization of antigen and subsequent presentation for further T cell activation14,15. Therefore, carbohydrate molecules play an important role in the study of immune responses; however, the use of these biomolecules often suffers from the lack of availability of structurally well-defined and pure carbohydrates. An automation platform based on iterative solution-phase reactions can enable rapid and controlled synthesis of these synthetically challenging molecules using significantly lower building block quantities than traditional solid-phase methods16,17.
Herein we report a protocol for the automated solution-phase synthesis of oligosaccharides such as mannose-based targeting ligands with fluorous solid-phase extraction for intermediate purification. After development of automated methods to make the carbohydrate-based targeting agent, we describe methods for their attachment on the surface of polyanhydride nanoparticles employing an automated robotic set up operated by LabVIEW as previously described10. Surface functionalization with carbohydrates has shown efficacy in targeting CLRs10,11 and increasing the throughput of the fabrication method to unearth the complexities associated with a multi-parametric system will be of great value (Figure 1a).

In this article, a high throughput method is presented for the synthesis of oligosaccharides and their attachment to the surface of polyanhydride nanoparticles for further use in targeting specific receptors on antigen presenting cells.

תפוקה גבוהה סינתזה של פחמימות functionalization של חלקיקים Polyanhydride

Transdisciplinary approaches involving areas such as material design, nanotechnology, chemistry, and immunology have to be utilized to rationally design ...

High Throughput Single-cell and Multiple-cell Micro-encapsulation

Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of controlled sizes. By combining drop generation techniques with cell and particle ordering, we demonstrate controlled encapsulation of cell-sized particles for efficient, continuous encapsulation. Using an aqueous particle suspension and immiscible fluorocarbon oil, we generate aqueous drops in oil with a flow focusing nozzle. The aqueous flow rate is sufficiently high to create ordering of particles which reach the nozzle at integer multiple frequencies of the drop generation frequency, encapsulating a controlled number of cells in each drop. For representative results, 9.9 &mu;m polystyrene particles are used as cell surrogates. This study shows a single-particle encapsulation efficiency Pk=1 of 83.7% and a double-particle encapsulation efficiency Pk=2 of 79.5% as compared to their respective Poisson efficiencies of 39.3% and 33.3%, respectively. The effect of consistent cell and particle concentration is demonstrated to be of major importance for efficient encapsulation, and dripping to jetting transitions are also addressed. 
Introduction 
Continuous media aqueous cell suspensions share a common fluid environment which allows cells to interact in parallel and also homogenizes the effects of specific cells in measurements from the media. High-throughput encapsulation of cells into picoliter-scale drops confines the samples to protect drops from cross-contamination, enable a measure of cellular diversity within samples, prevent dilution of reagents and expressed biomarkers, and amplify signals from bioreactor products. Drops also provide the ability to re-merge drops into larger aqueous samples or with other drops for intercellular signaling studies.1,2 The reduction in dilution implies stronger detection signals for higher accuracy measurements as well as the ability to reduce potentially costly sample and reagent volumes.3 Encapsulation of cells in drops has been utilized to improve detection of protein expression,4 antibodies,5,6 enzymes,7 and metabolic activity8 for high throughput screening, and could be used to improve high throughput cytometry.9 Additional studies present applications in bio-electrospraying of cell containing drops for mass spectrometry10 and targeted surface cell coatings.11 Some applications, however, have been limited by the lack of ability to control the number of cells encapsulated in drops. Here we present a method of ordered encapsulation12 which increases the demonstrated encapsulation efficiencies for one and two cells and may be extrapolated for encapsulation of a larger number of cells.
To achieve monodisperse drop generation, microfluidic "flow focusing" enables the creation of controllable-size drops of one fluid (an aqueous cell mixture) within another (a continuous oil phase) by using a nozzle at which the streams converge.13 For a given nozzle geometry, the drop generation frequency f and drop size can be altered by adjusting oil and aqueous flow rates Qoil and Qaq. As the flow rates increase, the flows may transition from drop generation to unstable jetting of aqueous fluid from the nozzle.14 
When the aqueous solution contains suspended particles, particles become encapsulated and isolated from one another at the nozzle. For drop generation using a randomly distributed aqueous cell suspension, the average fraction of drops Dk containing k cells is dictated by Poisson statistics, where Dk = &lambda;k exp(-&lambda;)/(k!) and &lambda; is the average number of cells per drop. The fraction of cells which end up in the "correctly" encapsulated drops is calculated using Pk = (k x Dk)/&Sigma;(k' x Dk'). The subtle difference between the two metrics is that Dk relates to the utilization of aqueous fluid and the amount of drop sorting that must be completed following encapsulation, and Pk relates to the utilization of the cell sample. As an example, one could use a dilute cell suspension (low &lambda;) to encapsulate drops where most drops containing cells would contain just one cell. While the efficiency metric Pk would be high, the majority of drops would be empty (low Dk), thus requiring a sorting mechanism to remove empty drops, also reducing throughput.15
Combining drop generation with inertial ordering provides the ability to encapsulate drops with more predictable numbers of cells per drop and higher throughputs than random encapsulation. Inertial focusing was first discovered by Segre and Silberberg16 and refers to the tendency of finite-sized particles to migrate to lateral equilibrium positions in channel flow. Inertial ordering refers to the tendency of the particles and cells to passively organize into equally spaced, staggered, constant velocity trains. Both focusing and ordering require sufficiently high flow rates (high Reynolds number) and particle sizes (high Particle Reynolds number).17,18 Here, the Reynolds number Re =uDh/&nu; and particle Reynolds number Rep =Re(a/Dh)2, where u is a characteristic flow velocity, Dh [=2wh/(w+h)] is the hydraulic diameter, &nu; is the kinematic viscosity, a is the particle diameter, w is the channel width, and h is the channel height. Empirically, the length required to achieve fully ordered trains decreases as Re and Rep increase. Note that the high Re and Rep requirements (for this study on the order of 5 and 0.5, respectively) may conflict with the need to keep aqueous flow rates low to avoid jetting at the drop generation nozzle. Additionally, high flow rates lead to higher shear stresses on cells, which are not addressed in this protocol. The previous ordered encapsulation study demonstrated that over 90% of singly encapsulated HL60 cells under similar flow conditions to those in this study maintained cell membrane integrity.12 However, the effect of the magnitude and time scales of shear stresses will need to be carefully considered when extrapolating to different cell types and flow parameters. The overlapping of the cell ordering, drop generation, and cell viability aqueous flow rate constraints provides an ideal operational regime for controlled encapsulation of single and multiple cells.
Because very few studies address inter-particle train spacing,19,20 determining the spacing is most easily done empirically and will depend on channel geometry, flow rate, particle size, and particle concentration. Nonetheless, the equal lateral spacing between trains implies that cells arrive at predictable, consistent time intervals. When drop generation occurs at the same rate at which ordered cells arrive at the nozzle, the cells become encapsulated within the drop in a controlled manner. This technique has been utilized to encapsulate single cells with throughputs on the order of 15 kHz,12 a significant improvement over previous studies reporting encapsulation rates on the order of 60-160 Hz.4,15 In the controlled encapsulation work, over 80% of drops contained one and only one cell, a significant efficiency improvement over Poisson (random) statistics, which predicts less than 40% efficiency on average.12
In previous controlled encapsulation work,12 the average number of particles per drop &lambda; was tuned to provide single-cell encapsulation. We hypothesize that through tuning of flow rates, we can efficiently encapsulate any number of cells per drop when &lambda; is equal or close to the number of desired cells per drop. While single-cell encapsulation is valuable in determining individual cell responses from stimuli, multiple-cell encapsulation provides information relating to the interaction of controlled numbers and types of cells. Here we present a protocol, representative results using polystyrene microspheres, and discussion for controlled encapsulation of multiple cells using a passive inertial ordering channel and drop generation nozzle.

Combining monodisperse drop generation with inertial ordering of cells and particles, we describe a method to encapsulate a desired number of cells or particles in a single drop at kHz rates. We demonstrate efficiencies twice exceeding those of unordered encapsulation for single- and double-particle drops.

קצב העברת נתונים גבוה תא יחיד ו מרובה תאים מיקרו אנקפסולציה

Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement ...

Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry

Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases1 and as a technology for regenerative medicine2. Unlike viruses, which have significant safety issues, polymeric nanoparticles can be designed to be non-toxic, non-immunogenic, non-mutagenic, easier to synthesize, chemically versatile, capable of carrying larger nucleic acid cargo and biodegradable and/or environmentally responsive. Cationic polymers self-assemble with negatively charged DNA via electrostatic interaction to form complexes on the order of 100 nm that are commonly termed polymeric nanoparticles. Examples of biomaterials used to form nanoscale polycationic gene delivery nanoparticles include polylysine, polyphosphoesters, poly(amidoamines)s and polyethylenimine (PEI), which is a non-degradable off-the-shelf cationic polymer commonly used for nucleic acid delivery1,3 . Poly(beta-amino ester)s (PBAEs) are a newer class of cationic polymers4 that are hydrolytically degradable5,6 and have been shown to be effective at gene delivery to hard-to-transfect cell types such as human retinal endothelial cells (HRECs)7, mouse mammary epithelial cells8, human brain cancer cells9 and macrovascular (human umbilical vein, HUVECs) endothelial cells10.
A new protocol to characterize polymeric nanoparticles utilizing nanoparticle tracking analysis (NTA) is described. In this approach, both the particle size distribution and the distribution of the number of plasmids per particle are obtained11. In addition, a high-throughput 96-well plate transfection assay for rapid screening of the transfection efficacy of polymeric nanoparticles is presented. In this protocol, poly(beta-amino ester)s (PBAEs) are used as model polymers and human retinal endothelial cells (HRECs) are used as model human cells. This protocol can be easily adapted to evaluate any polymeric nanoparticle and any cell type of interest in a multi-well plate format.

A protocol for nanoparticle tracking analysis (NTA) and high-throughput flow cytometry to evaluate polymeric gene delivery nanoparticles is described. NTA is utilized to characterize the nanoparticle particle size distribution and the plasmid per particle distribution. High-throughput flow cytometry enables quantitative transfection efficacy evaluation for a library of gene delivery biomaterials.

הערכת משלוח גן פולימרית חלקיקים על ידי Nanoparticle מעקב ניתוח וזרימת cytometry תפוקה גבוהה

Non-viral gene delivery using polymeric nanoparticles has emerged as an attractive approach for gene therapy to treat genetic diseases1 and as a ...

Synthesis of Gold Nanoparticle Integrated Photo-responsive Liposomes and Measurement of Their Microbubble Cavitation upon Pulse Laser Excitation

Photo-responsive nanoparticles (NPs) have received considerable attention because of their potential in providing spatial, temporal, and dosage control over the drug release. However, most of the relevant technologies are still in the development process and are unprocurable by clinics. Here, we describe a facile fabrication of these photo-responsive NPs with commercially available gold NPs and thermo-responsive liposomes. Calcein is used as a model drug to evaluate the encapsulation efficiency and the release kinetic profile upon heat/light stimulation. Finally, we show that this photo-triggered release is due to the membrane disruption caused by microbubble cavitation, which can be measured with hydrophone.

This protocol describes a simple preparation method for gold nanoparticle integrated photo-responsive liposomes with the commercially available materials. It also shows how to measure the microbubble cavitation process of the synthesized liposomes upon the treatment of pulsed laser.

סינתזה של משולב זהב Nanoparticle תמונה המגיבים ליפוזומים ומדידה של microbubble Cavitation שלהם על עירור לייזר דופק

Photo-responsive nanoparticles (NPs) have received considerable attention because of their potential in providing spatial, temporal, and dosage control ...

Film Extrusion of Crambe abyssinica/Wheat Gluten Blends

Crambe abyssinica is a plant with potential for use in industrial (non-food) plant oil production. The side stream from this oil production is a high-protein crambe meal that has limited value, as it is not fit for food or feed use. However, it contains proteins that could potentially make it a suitable raw material for higher-value products. The purpose of this study was to find methods of making this side stream into extruded films, showing that products with a higher value can be produced. The study mainly considered the development of material compositions and methods of preparing and extruding the material. Wheat gluten was added as a supportive protein matrix material, together with glycerol as a plasticizer and urea as a denaturant. The extrudate was evaluated with respect to mechanical (tensile testing) and oxygen barrier properties, and the extrudate structure was revealed visually and by scanning electron microscopy. A denser, more homogeneous material had a lower oxygen transmission rate, higher strength, and higher extensibility. The most homogeneous films were made at an extruder die temperature of 125-130 &#176;C. It is shown here that a film can be extruded with promising mechanical and oxygen barrier properties, the latter especially after a final compression molding step.

Film Extrusion of Crambe abyssinica/Wheat Gluten Blends

The side stream from plant oil production of Crambe abyssinica has limited value. The purpose of this study was to find methods for extruding materials based on this side stream, demonstrating that products with a higher value can be produced. The extrudates were found to have promising properties.

סרטים שחול של<em&gt; Crambe abyssinica</em&gt; / חיטה גלוטן תערובות

Crambe abyssinica is a plant with potential for use in industrial (non-food) plant oil production. The side stream from this oil production is a ...

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

מגנטי תרמי רגיש פולי (<em&gt; N</em&gt; -isopropylacrylamide) מבוססי microgels עבור מגנטית מופעל מבוקר שחרור

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...