Este trabalho é apoiado como parte do Centro de Nível Atômico Catalisador projeto, um Centro de Pesquisa de Energia Frontier financiado pelo Departamento de Energia dos EUA, Escritório de Ciência, Instituto de ciências básicas da energia sob Prêmio Número DE-SC0001058 e também apoiado pelo Conselho de Regents sob concessões número prêmio LEQSF (2009-14)-EFRC-MATCH e LEDSF-EPS (2012)-OPT-IN-15. Operações MRCAT são suportados pelo Departamento de Energia e as instituições membros MRCAT. O uso da Advanced Photon Source no ANL é apoiado pelo Departamento de Energia dos EUA, Escritório de Ciência, Instituto de ciências básicas da energia, sob Contrato n º DE-AC02-06CH11357. O apoio financeiro para JTM foi fornecido como parte do Instituto de Atom-eficientes Transformações Químicas (IACT), um Centro de Pesquisa de Energia Frontier financiado pelo Departamento de Energia dos EUA, Escritório de Ciência, Instituto de ciências básicas da energia.

Millifluidics set-up: Compre um chip millifluidic (feito de poliéster polímero tereftalato) de Microplumbers Microsciences LLC, que tem canais de serpentinas com dimensões de 2 mm (W) x 0,15 milímetros (H) x 220 mm (L). Use FEP Tubos com dimensões de 0,25 mm Dl, 1/16 em OD, para ligar o chip para a bomba. Use duas bombas diferentes para as duas experiências diferentes. Utilização P-bomba para a primeira experiência (nanopartículas de cobre) e o dispositivo millifluidic para a segunda experiência (nanopartículas de ouro). Para minimizar o problema das bolhas de gás no interior dos canais, preparados NaBH4 solução foi deixada em aberto a repousar durante ~ 10-15 min antes do bombeamento para o chip de modo a que as bolhas de gás escapar a partir da solução. Este passo foi seguido por todos os nossos experimentos. 1. Síntese de ultra-pequenas de cobre Nano Clusters (UCNCs) <ol><li> Produtos químicos necessários: obter o cobre (II) Nitrahidrato te, borohidreto de sódio, pelotas de hidróxido de sódio e O-[2 - (3-mercaptopropionylamino) etil]-O&#39;-metilpolietileno glicol (PM = 5.000) [MPEG] e utilizar todos os produtos químicos sem purificação adicional. Use água nanopura (18,2 M-cm) para o experimento. </li><li> Use P-bomba regulada sob pressão de nitrogênio para o experimento. Testar as bombas com água como solvente, a diferentes pressões, antes do ensaio para correlacionar com os caudais correspondentes (ml / hr). Lavar o reactor millifluidic e tubos com água desionizada antes do início da experiência. </li><li> Dissolve-se 174 mg (0,95 mmol) de cobre (II) e nitrato de 610 mg (0,122 mmol) de O-[2 - (3-mercaptopropionylamino) etil]-O&#39;-metilpolietileno glicol em 28 ml de água nanopura e mantê-los numa frasco para ser ligada com um canal de entrada </li><li> Manter uma outra solução de 111 mg (2,93 mmol) de borohidreto de sódio e 102 mg (2,78 mmol) de hidróxido de sódio em 28 ml (pH ~ 13) em um frasco diferente e ligá-la com ooutro canal de entrada. </li><li> Fluxo ambas as soluções simultaneamente dentro do reator millifluidic em diferentes caudais (dados abaixo) e recolher os UCNCs resultantes na saída em frasco de vidro. Purgar a solução com nitrogênio e armazená-lo sob azoto. </li><li> Operar as bombas, sob diferentes pressões constantes de 50 mbar (6,81 ml / h), 100 mbar (14,31 ml / h), 200 mbar (32,7 ml / h) e 300 mbar (51,4 ml / h) à temperatura ambiente para a síntese de UCNCs em diferentes caudais. </li></ol> Enquanto o procedimento de síntese foi demonstrado utilizando o conjunto millifluidic-se com P-bomba, pode também ser realizada utilizando o dispositivo millifluidic de mão de Millifluidica. 2. Tempo Resolvido in situ estudos cinéticos sobre a formação de nanopartículas de ouro <ol><li> Produtos químicos necessários: obter ácido chloroauric (HAuCl 4 3H 2 O). Meso-2 ,3-dimercaptosuccinic (DMSA) e borohidreto de sódio &amp; #160, e utilizar todos os produtos químicos sem purificação adicional. Use água nanopura (18,2 M-cm) para o experimento. </li><li> Use alta precisão, bombas de seringa, de pulsação livre totalmente automatizados a fluir os líquidos dentro do chip. Teste as bombas com água como solvente em diferentes caudais antes da experiência para otimizar o fluxo necessário. </li><li> Prepare soluções padrão de (i) HAuCl 4. 3H 2 O (10 mmol, 118,2 mg/30 ml) e (ii) o DMSA (20 mmol, 109,2 mg/30 ml) com 50 mg de hidróxido de sódio (pH 12) no nanopura água. </li><li> Alimentar as duas soluções através de duas seringas separadas para o chip millifluidic a um caudal constante de 10 ml / h utilizando a bomba automatizado. </li><li> Par o chip millifluidic à linha de feixe sincrotrão usando uma fase de metal que tem acesso ao movimento nas direcções XYZ e recolher os dados XAS em zonas diferentes no chip como as soluções foram bombeadas através do chip. </li></ol> Enquanto o &lt;em&gt; em análise situ procedimento foi demonstrada usando o millifluidic set-up com P-bomba, ela também pode ser efectuado através de um dispositivo millifluidic de mão. 3. Fluxo Contínuo Ouro Catálise Este procedimento foi demonstrada utilizando um dispositivo millifluidic de mão. <ol><li> Produtos químicos necessários: Obtenção de ácido cloroáurico (HAuCl 4 3H 2 O.), Meso-2 ,3-dimercaptossuccínico (DMSA), borohidreto de sódio, 4-nitrofenol, 4-aminofenol e de utilizar todos os produtos químicos sem purificação adicional. Use água nanopura (18,2 M-cm) para o experimento. </li><li> Preparação do catalisador:. Prepare soluções padrão de HAuCl 4 3H 2 O (10 mmol, 118,2 mg/30 ml), DMSA (20 mmol, 109,2 mg/30 ml) e NaBH4 (10 mmol, 11,34 mg/30 ml) em Nanopure água. </li><li> Tome 10 ml cada uma HAuCl 4 e soluções DMSA em dois frascos separados e fluxo ªlos dentro do chip usando o dispositivo millifluidic de mão com uma taxa de fluxo uniforme de 12 ml / h para 45 min. </li><li> Fluxo de 10 mmol de NaBH4 dentro do chip em 12 caudal mL / h durante 15 minutos para reduzir o Au (I) em Au (0). </li><li> Finalmente, lava-se a lasca com água nanopura durante 30 minutos à mesma taxa de fluxo antes de realizar as experiências de catálise. </li><li> Reacção de catálise: Realizar a reacção de conversão química (redução) de 4-nitrofenol (4-NP) em 4-aminofenol (4-AP) no catalisador de ouro (preparado acima) revestido canal millifluidic como dado abaixo. </li><li> Misturar 15 ml de solução de 9 x 10 -5 mol de 4-NP, com 3,3 ml de 0,65 mol de NaBH4 de modo a formar uma solução de iões de 4-nitrofenolato (4-INF). </li><li> Filtrar a solução resultante sobre o catalisador de ouro depositados dentro de chip com uma taxa de fluxo constante de 5 ml / h para avaliar a actividade catalítica. Analisar os espectros de UV-Vis dos produtos recolhidos no intervalo de comprimento de onda de 250-500 nm para confirmar a conversão de 4-NP. </li><li> Estimativa da actividade catalítica da reacção através da obtenção da curva de calibração de 4-INF. Curva de calibração pode ser adquirido através da representação gráfica da intensidade de absorção observado experimentalmente (I) de 4-NPI em diferentes concentrações padrão. As alturas dos picos (a 399 nm) para as curvas de absorção de UV-Vis representa a intensidade de absorção (I) e valores de acordo com a lei de Lambert Beer, qualquer mudança no valor da altura do pico que mostram a mudança correspondente na sua concentração. Portanto, estimar a actividade catalítica por encontrar a diferença nas concentrações iniciais e finais do reagente a partir da curva de calibração. Por exemplo, se a altura do pico é uma unidade (Figura 6) que corresponde a uma conversão catalítica de 90% (com base na curva de calibração). </li></ol>

<ol>
	<li>Song, Y., Hormes, J., Kumar, C. S. S. R. <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+Nanomaterials.">Microfluidic Synthesis of Nanomaterials.</a> Small. 4 (6), 698-711 (2008).</li><li>Huebner, A., Sharma, S., Srisa-Art, M., Hollfelder, F., Edel, J. B., DeMello, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microdroplets:+a+sea+of+applications.">Microdroplets: a sea of applications.</a> Lab Chip. 8, 1244-1254 (2008).</li><li>Helen, S., Delai, L. C., Rustem, F. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactions+in+Droplets+in+Microfluidic+Channels.">Reactions in Droplets in Microfluidic Channels.</a> Angew. Chem. Int. Ed. 45, 7336-7356 (2006).</li><li>Marre, S., Jensen, K. F. <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+nanostructures+in+microfluidic+systems.">Synthesis of nanostructures in microfluidic systems.</a> Chem. Soc. Rev. 39, 1183-1202 (2010).</li><li>Theberge, A. B., Courtois, F., Schaerli, Y., Fischlechner, M., Abell, C., Hollfelder, F., Huck, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microdroplets+in+microfluidics:+an+evolving+platform+for+discoveries+in+chemistry+and+biology.">Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology.</a> Angew. Chem. Int. Ed. 49 (34), 5846-5868 (2010).</li><li>Nicolas, L., Flavie, S., Pierre, G., Pascal, P., Annie, C., Bertrand, P., Cindy, H., Patrick, M., Samuel, M., Thomas, D., Cyril, A., Pascale, S., Laurent, P., Christopher, G., Emmanuel, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Some+recent+advances+in+the+design+and+the+use+of+miniaturized+droplet-based+continuous+process:+Applications+in+chemistry+and+high-pressure+microflows.">Some recent advances in the design and the use of miniaturized droplet-based continuous process: Applications in chemistry and high-pressure microflows.</a> Lab Chip. 11, 779 (2011).</li><li>Biswas, S., Miller, J. T., Li, Y., Nandakumar, K., Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developing+Millifluidic+Platform+for+Synthesis+of+Ultra-small+Nanoclusters+(UNCs):+Ultra-small+Copper+Nanoclusters+(UCNCs)+as+a+Case+Study.">Developing Millifluidic Platform for Synthesis of Ultra-small Nanoclusters (UNCs): Ultra-small Copper Nanoclusters (UCNCs) as a Case Study.</a> Small. 8 (5), 688-698 (2012).</li><li>Li, Y., Sanampudi, A., Reddy, V. R., Biswas, S., Nandakumar, K., Yamane, D. G., Goettert, J. S., Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Size+Evolution+of+Gold+Nanoparticles+in+a+Millifluidic+Reactor.">Size Evolution of Gold Nanoparticles in a Millifluidic Reactor.</a> Phys. Chem. Phys. 13 (1), 177-182 (2012).</li><li>Li, Y., Yamane, D. G., Li, S., Biswas, S., Reddy, R., Goettert, J. S., Nandakumar, K., Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Geometric+Optimization+of+Liquid-Liquid+Slug+Flow+in+a+Flow-focusing+Millifluidic+Device+for+Synthesis+of+Nanomaterials.">Geometric Optimization of Liquid-Liquid Slug Flow in a Flow-focusing Millifluidic Device for Synthesis of Nanomaterials.</a> Chem. Eng. J. 217, 447-459 (2013).</li><li>Zinoveva, S., De Silva, R., Louis, R. D., Datta, P., Kumar, C. S. S. R., Goettert, J., Hormes, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+wet+chemical+synthesis+of+Co+nanoparticles+in+a+microreactor+system:+A+time-resolved+investigation+by+X-ray+absorption+spectroscopy.">The wet chemical synthesis of Co nanoparticles in a microreactor system: A time-resolved investigation by X-ray absorption spectroscopy.</a> Nucl. Instrum. Methods Phys. Res. A. 582, 239-241 (2007).</li><li>Krishna, K. S., Navin, C. V., Biswas, S., Singh, V., Ham, K., Bovenkamp, G. L., Theegala, C. S., Miller, J. T., Spivey, J., Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Millifluidics+for+Time-resolved+Mapping+of+the+Growth+of+Gold+Nanostructures.">Millifluidics for Time-resolved Mapping of the Growth of Gold Nanostructures.</a> J. Am. Chem. Soc. 135 (14), 5450-5456 (2013).</li><li>Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Microfluidic Devices in nanotechnology-Fundamental Concepts. , (2010).</li><li>Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Microfluidic Devices in nanotechnology-Fundamental Concepts. , (2010).</li><li>Meille, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+on+Methods+to+Deposit+Catalysts+on+Structured+Surfaces.">Review on Methods to Deposit Catalysts on Structured Surfaces.</a> Appl. Catal. A Gen. 315, 1-17 (2006).</li><li>Shin, W. C., McDonald, J. A., Zhao, S., Besser, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Etching+Characteristics+of+a+Micromachined+Chemical+Reactor+Using+Inductively+Coupled+Plasma.">Etching Characteristics of a Micromachined Chemical Reactor Using Inductively Coupled Plasma.</a> , p357 (2002).</li><li>Abahmane, L., K&#246;hler, J. M., Gro&#223;, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gold-nanoparticle-catalyzed+synthesis+of+propargylamines:+the+traditional+A3-multicomponent+reaction+performed+as+a+two-step+flow+process.">Gold-nanoparticle-catalyzed synthesis of propargylamines: the traditional A3-multicomponent reaction performed as a two-step flow process.</a> Chem. Eur. J. 17, 3005-3010 (2011).</li><li>Abahmane, L., Knauer, A., Ritter, U., K&#246;hler, J. M., Gro&#223;, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heterogeneous+Catalyzed+Pyridine+Synthesis+using+Montmorillionite+and+Nanoparticle-Impregnated+Alumina+in+a+Continuous+Micro+Flow+System.">Heterogeneous Catalyzed Pyridine Synthesis using Montmorillionite and Nanoparticle-Impregnated Alumina in a Continuous Micro Flow System.</a> Chem. Eng. Technol. 32, 1799-1805 (2009).</li><li>Abahmane, L., Knauer, A., K&#246;hler, J. M., Gro&#223;, G. A. <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+polypyridine+derivatives+using+alumina+supported+gold+nanoparticles+under+micro+continuous+flow+conditions.">Synthesis of polypyridine derivatives using alumina supported gold nanoparticles under micro continuous flow conditions.</a> Chem. Eng. J. 167, 519-526 (2011).</li><li>Negishi, Y., Tsukuda, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-Pot+Preparation+of+Subnanometer-Sized+Gold+Clusters+via+Reduction+and+Stabilization+by+meso-2,3-Dimercaptosuccinic+Acid.">One-Pot Preparation of Subnanometer-Sized Gold Clusters via Reduction and Stabilization by meso-2,3-Dimercaptosuccinic Acid.</a> J. Am. Chem. Soc. 125, 4046-4047 (2003).</li><li>Abou-Hassan, A., Sandre, O., Cabuil, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidics+in+Inorganic+Chemistry.">Microfluidics in Inorganic Chemistry.</a> Angew. Chem. Int. Ed. 49, 6268-6286 (2010).</li><li>Jiang, D., Walter, M., Dai, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gold+Sulfide+Nanoclusters:+A+Unique+Core-In-Cage+Structure.">Gold Sulfide Nanoclusters: A Unique Core-In-Cage Structure.</a> Chem. Eur. J. 16, 4999-5003 (2010).</li><li>Kuroda, K., Ishida, T., Haruta, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of+4-nitrophenol+to+4-aminophenol+over+Au+nanoparticles+deposited+on+PMMA.">Reduction of 4-nitrophenol to 4-aminophenol over Au nanoparticles deposited on PMMA.</a> J. Mol. Catal. A Chem. 298, 7-11 (2009).</li><li>Navin, C. V., Krishna, K. S., Theegala, C. S., Kumar, C. S. S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lab-on-a-chip+devices+for+gold+nanoparticle+synthesis+and+their+role+as+a+catalyst+support+for+continuous+flow+catalysis.">Lab-on-a-chip devices for gold nanoparticle synthesis and their role as a catalyst support for continuous flow catalysis.</a> Nanotech. Rev. , (2013).</li><li>Shahbazali, E., Hessel, V., No&#235;l, T., Wang, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metallic+nanoparticles+made+in+flow+and+their+catalytic+applications+in+organic+synthesis.">Metallic nanoparticles made in flow and their catalytic applications in organic synthesis.</a> Nanotech. Rev. , (2013).</li></ol>

Todos os autores, exceto CSSR Kumar declaram que não têm interesses financeiros concorrentes. C. SSR Kumar é o fundador da empresa Millifluidica LLC.

Os UCNCs foram formados pela reacção de redução de nitrato de cobre, com borohidreto de sódio na presença do polímero de nivelamento agente de O-[2 - (3-Mercaptopropionylamino) etil]-O&#39;-metilpolietileno glicol (PM = 5.000) [MPEG]. A reacção foi realizada dentro do reator de chips millifluidic em diferentes taxas de-fluxo, como 6,8 ml / h, 14,3 ml / h, 32,7 ml / h, e 51,4 ml / h para estudar o efeito das taxas de-fluxo nas UCNCs formados. Os respectivos tempos de residência para os caudais acima são 47,49,...

Dispositivos lab-on-a-chip (LOC) para síntese química têm demonstrado vantagem significativa em termos de aumento de massa e calor de transferência, controle de reação superior, alto rendimento e ambiente de operação mais segura 1. Estes dispositivos podem ser classificados em fluidos de chips baseados e dispositivos fluídicos nonchip base. Entre os fluidos à base de chips, microfluídica é bem investigado e um tema bem abordado na literatura 2-5. Sistemas baseados LOC Nonchip utilizar reactores tubulares 6. Convencionalmente, os sistemas microfluídicos são usados ​​para controle preciso e manipulação de fluidos que são geometricamente restringidas a escala submillimeter. Recentemente, introduziu o conceito de millifluidics à base de chips, que podem ser utilizados para a manipulação de fluidos em canais em escala milimétrica (largura ou profundidade ou em ambos os canais são, pelo menos, um milímetro de tamanho) 7-9. Além disso, os chips millifluidic são relativamente fáceis de fabricar while oferecendo controle similar sobre caudais e manipulação de reagentes. Esses chips também pode ser operado com caudais mais elevados, criando tempos de residência menores, assim, oferecendo a possibilidade de scale-up de síntese controlada de nanopartículas com estreita distribuição de tamanho. Como exemplo, foi demonstrado recentemente a síntese de ultra-pequenas nanopartículas de cobre e caracterizado deles usando in situ de raios-X a espectroscopia de absorção, bem como ETM. Capacidade de obter pequenos tempos de residência no interior dos canais millifluidic em combinação com a utilização do MPEG, o qual é muito eficiente bidentado PEGuilado agente estabilizador para a formação de colóides estáveis ​​de nanopartículas de cobre 7. Para além da síntese de produtos químicos e os nanomateriais, os millifluidics poderia oferecer, devido ao maior volume e concentração na área da sonda, uma plataforma sintético que é mais generalizada e eficiente para os estudos cinéticos e resolvidos no tempo e também obtida atraves melhor relação sinal-ruído de sistemas microfluídicos 7,10. Mostramos a utilização de chip de millifluidic como um exemplo para a análise de cada vez determinado o crescimento de nanoestruturas de ouro a partir da solução utilizando xas in situ com uma resolução de tempo tão pequeno como 5 mseg 11. Além disso, a maioria das micro-reactores desenvolvido até à data para aplicações de catálise são baseados em 12,13 de silício. O seu fabrico caro, além de pequenas quantidades geradas torna-os inadequados para a fabricação em larga escala. Os dois métodos gerais para o revestimento dos canais com nanocatalisadores - químicas e físicas, muitas vezes referida como processos de revestimento de silicone, estão atualmente em voga 14,15. Além microfabricação caro, o entupimento dos canais torna catálise micro reactor pode ser inadequado para a fabricação em grande escala. Embora microreatores têm sido utilizados para a catálise heterogênea em micro contínuas de fluxo através de processos earlier 16-18, a capacidade de controlar a dimensão e morfologia dos catalisadores nanoestruturados ouro incorporados em canais de fluxo contínuo nunca foi explorado antes. Recentemente, desenvolveu uma tecnologia para o revestimento dos canais millifluidic com catalisadores Au, ter controlado a morfologia e as dimensões de nano (Figura 5) 11, para a realização da catálise de reacções químicas industrialmente importantes. Como exemplo temos demonstrado conversão de 4-nitrofenol em 4-aminofenol catalisada por ouro nanoestruturada revestido dentro dos canais millifluidic. Considerando-se que um único chip reator millifluidic pode produzir caudais de 50-60 ml / hr, 7 de alto rendimento e síntese controlada de produtos químicos é possível através de operação de fluxo contínuo ou de processamento paralelo. A fim de capitalizar sobre as possibilidades dos millifluidics oferecer, com poucos exemplos descritos acima, também queremos demonstrar um user-friendlymillifluidic dispositivo que é portátil e tem os todos os componentes necessários, tais como batatas fritas millifluidic, colectores, controladores de fluxo, bombas e ligações eléctricas integrado. Tal dispositivo millifluidic, como mostrado na Figura 7, está agora disponível a partir da empresa Millifluidica LLC ( <a href="http://www.millifluidica.com" target="_blank">www.millifluidica.com</a> ). O manuscrito também fornece protocolos que utilizam o dispositivo millifluidic de mão, como descrito abaixo, para a síntese controlada de nanomateriais, análise resolvida no tempo de mecanismos de reacção e catálise de fluxo contínuo.

<table border="1">
	<tbody>
		<tr>
			<td>Copper (II) nitrate hydrate</td>
			<td>Sigma-Aldrich</td>
			<td>13778-31-9</td>
			<td>99.999% pure</td>
		</tr>
		<tr>
			<td>O-[2-(3-mercaptopropionylamino)ethyl]-O&#8242;-methylpolyethylene glycol</td>
			<td>Sigma-Aldrich</td>
			<td>401916-61-8&#160;</td>
			<td>MW=5,000</td>
		</tr>
		<tr>
			<td>HAuCl4.3H2O (Chloroauric acid)</td>
			<td>Sigma-Aldrich</td>
			<td>27988-77-8&#160;</td>
			<td>99.999% pure</td>
		</tr>
		<tr>
			<td>meso-2,3-dimercaptosuccinic acid (DMSA)</td>
			<td>Sigma-Aldrich</td>
			<td>304-55-2</td>
			<td>~98% pure</td>
		</tr>
		<tr>
			<td>4-Nitrophenol</td>
			<td>Sigma-Aldrich</td>
			<td>100-02-7&#160;</td>
			<td>spectrophotometric grade</td>
		</tr>
		<tr>
			<td>4-Aminophenol</td>
			<td>Sigma-Aldrich</td>
			<td>123-30-8&#160;</td>
			<td>&#62;99% pure (HPLC grade)</td>
		</tr>
		<tr>
			<td>Sodium borohydride</td>
			<td>Sigma-Aldrich</td>
			<td>16940-66-2&#160;</td>
			<td>98% pure</td>
		</tr>
		<tr>
			<td>Sodium hydroxide pellets</td>
			<td>Sigma-Aldrich</td>
			<td>1310-73-2&#160;</td>
			<td>99.99% pure</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>[header]</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>EQUIPMENT</td>
		</tr>
		<tr>
			<td>Millifluidic Chips</td>
			<td>Microplumbers Microsciences LLC</td>
			<td>SDC-01</td>
			<td>Made from polyester terephthalate polymer</td>
		</tr>
		<tr>
			<td>Pressure Pump</td>
			<td>Mitos P-Pump, Dolomite</td>
			<td>3200016</td>
			<td></td>
		</tr>
		<tr>
			<td>Automated Syringe Pump</td>
			<td>Cetoni Automation and Microsystems, GmbH</td>
			<td></td>
			<td>Syringe pump neMESYS</td>
		</tr>
		<tr>
			<td>UV-3600 UV-VIS-NIR Spectrophotometer</td>
			<td>Shimadzu</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hand-held Millifluidic Device</td>
			<td>Millifluidica</td>
			<td>SCMD-1008</td>
			<td>Figure 7</td>
		</tr>
	</tbody>
</table>

millifluidics for chemical synthesis and time-resolved mechanistic studies

Procedimentos utilizando dispositivos millifluidic para a síntese química e estudos mecanicistas resolvida no tempo são descritos tomando três exemplos. Em primeiro lugar, a síntese de ultra-pequenas nanopartículas de cobre é descrito. O segundo exemplo fornece a sua utilidade para a investigação de tempo resolvido cinética de reações químicas através da análise de formação de nanopartículas de ouro utilizando in situ de raios-X espectroscopia de absorção. O último exemplo demonstra a catálise de reacções de fluxo contínuo no interior do canal millifluidic revestidas com catalisador nanoestruturada.

Bem disperso e nanopartículas de cobre de tamanho uniforme, com uma distribuição de tamanho estreita foram obtidos utilizando a instalação de chips millifluidic (Fig. 1a). Os diferentes caudais utilizados para a síntese de não ter um efeito significativo sobre o tamanho dos aglomerados. No entanto, com o aumento da taxa de fluxo, não é observável uma melhoria no estreitamento da distribuição de tamanho. UCNCs com uma melhor distribuição de tamanhos estreita foram obtidos com uma taxa de fluxo de 32,7 ml / ...

Watch this Scientific Journal Video about Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies at JoVE.com

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Millifluidic dispositivos são utilizados para a síntese controlada de nanomateriais, análise resolvida no tempo de mecanismos de reacção e catálise de fluxo contínuo.

Millifluidics para síntese química e resolvida no tempo estudos sobre os mecanismos

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the ...

millifluidics-for-chemical-synthesis-time-resolved-mechanistic

Research

Education

JoVE Journal

JoVE Core

Physics

Bioengineering

Unit 1

Work and Kinetic Energy

SCIENTISTS IN ACTION

11.1K visualizações.  Louisiana State University.  Millifluidic dispositivos são utilizados para a síntese controlada de nanomateriais, análise resolvida no tempo de mecanismos de reacção e catálise de fluxo contínuo. 

Vídeo: Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

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

Polyanhydrides are a class of biomaterials with excellent biocompatibility and drug delivery capabilities. While they have been studied extensively with conventional one-sample-at-a-time synthesis techniques, a more recent high-throughput approach has been developed enabling the synthesis and testing of large libraries of polyanhydrides1. This will facilitate more efficient optimization and design process of these biomaterials for drug and vaccine delivery applications. The method in this work describes the combinatorial synthesis of biodegradable polyanhydride film and nanoparticle libraries and the high-throughput detection of protein release from these libraries. In this robotically operated method (Figure 1), linear actuators and syringe pumps are controlled by LabVIEW, which enables a hands-free automated protocol, eliminating user error. Furthermore, this method enables the rapid fabrication of micro-scale polymer libraries, reducing the batch size while resulting in the creation of multivariant polymer systems. This combinatorial approach to polymer synthesis facilitates the synthesis of up to 15 different polymers in an equivalent amount of time it would take to synthesize one polymer conventionally. In addition, the combinatorial polymer library can be fabricated into blank or protein-loaded geometries including films or nanoparticles upon dissolution of the polymer library in a solvent and precipitation into a non-solvent (for nanoparticles) or by vacuum drying (for films). Upon loading a fluorochrome-conjugated protein into the polymer libraries, protein release kinetics can be assessed at high-throughput using a fluorescence-based detection method (Figures 2 and 3) as described previously1. This combinatorial platform has been validated with conventional methods2 and the polyanhydride film and nanoparticle libraries have been characterized with 1H NMR and FTIR. The libraries have been screened for protein release kinetics, stability and antigenicity; in vitro cellular toxicity, cytokine production, surface marker expression, adhesion, proliferation and differentiation; and in vivo biodistribution and mucoadhesion1-11. The combinatorial method developed herein enables high-throughput polymer synthesis and fabrication of protein-loaded nanoparticle and film libraries, which can, in turn, be screened in vitro and in vivo for optimization of biomaterial performance.

This method describes the combinatorial synthesis of biodegradable polyanhydride film and nanoparticle libraries and the high-throughput detection of protein release from these libraries.

Síntese combinatória de alta capacidade e liberação de proteínas a partir de polímero de Cinema e Bibliotecas Nanopartículas

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

Bioengenharia

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.

Alta capacidade de síntese de hidratos de carbono e funcionalização de nanopartículas polianidrido

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

Microfabrication of Nanoporous Gold Patterns for Cell-material Interaction Studies

Nanostructured materials with feature sizes in tens of nanometers have enhanced the performance of several technologies, including fuel cells, biosensors, biomedical device coatings, and drug delivery tools. Nanoporous gold (np-Au), produced by a nano-scale self-assembly process, is a relatively new material that exhibits large effective surface area, high electrical conductivity, and catalytic activity. These properties have made np-Au an attractive material to scientific community. Most studies on np-Au employ macro-scale specimens and focus on fundamental science of the material and its catalytic and sensor applications. The macro-scale specimens limit np-Au's potential in miniaturized systems, including biomedical devices. In order to address these issues, we initially describe two different methods to micropattern np-Au thin films on rigid substrates. The first method employs manually-produced stencil masks for creating millimeter-scale np-Au patterns, while the second method uses lift-off photolithography to pattern sub-millimeter-scale patterns. As the np-Au thin films are obtained by sputter-deposition process, they are compatible with conventional microfabrication techniques, thereby amenable to facile integration into microsystems. These systems include electrically-addressable biosensor platforms that benefit from high effective surface area, electrical conductivity, and gold-thiol-based surface bioconjugation. We describe cell culture, immunostaining, and image processing techniques to quantify np-Au's interaction with mammalian cells, which is an important performance parameter for some biosensors. We expect that the techniques illustrated here will assist the integration of np-Au in platforms at various length-scales and in numerous applications, including biosensors, energy storage systems, and catalysts.

We report on techniques to micropattern nanoporous gold thin films via stencil printing and photolithography, as well as methods to culture cells on the microfabricated patterns. In addition, we describe image analysis methods to characterize morphology of the material and the cultured cells using scanning electron and fluorescence microscopy techniques.

Microfabricação de Padrões de Ouro Nanoporosos para celular-primas estudos de interacção

Nanostructured materials with feature sizes in tens of nanometers have enhanced the performance of several technologies, including fuel cells, biosensors, ...

Synthesis of an Intein-mediated Artificial Protein Hydrogel

We present the synthesis of a highly stable protein hydrogel mediated by a split-intein-catalyzed protein trans-splicing reaction. The building blocks of this hydrogel are two protein block-copolymers each containing a subunit of a trimeric protein that serves as a crosslinker and one half of a split intein. A highly hydrophilic random coil is inserted into one of the block-copolymers for water retention. Mixing of the two protein block copolymers triggers an intein trans-splicing reaction, yielding a polypeptide unit with crosslinkers at either end that rapidly self-assembles into a hydrogel. This hydrogel is very stable under both acidic and basic conditions, at temperatures up to 50 &#176;C, and in organic solvents. The hydrogel rapidly reforms after shear-induced rupture. Incorporation of a &#34;docking station peptide&#34; into the hydrogel building block enables convenient incorporation of &#34;docking protein&#34;-tagged target proteins. The hydrogel is compatible with tissue culture growth media, supports the diffusion of 20 kDa molecules, and enables the immobilization of bioactive globular proteins. The application of the intein-mediated protein hydrogel as an organic-solvent-compatible biocatalyst was demonstrated by encapsulating the horseradish peroxidase enzyme and corroborating its activity.

We present the synthesis of a split-intein-mediated protein hydrogel. The building blocks of this hydrogel are two protein copolymers each containing a subunit of a trimeric protein that serves as a crosslinker and one half of a split intein. Mixing of the two protein copolymers triggers an intein trans-splicing reaction, yielding a polypeptide unit that self-assembles into a hydrogel. This hydrogel is highly pH- and temperature-stable, compatible with organic solvents, and easily incorporates functional globular proteins.

Síntese de uma proteína artificial intein mediada Hidrogel

We present the synthesis of a highly stable protein hydrogel mediated by a split-intein-catalyzed protein trans-splicing reaction. The building blocks of ...

Synthesis of Keratin-based Nanofiber for Biomedical Engineering

Electrospinning, due to its versatility and potential for applications in various fields, is being frequently used to fabricate nanofibers. Production of these porous nanofibers is of great interest due to their unique physiochemical properties. Here we elaborate on the fabrication of keratin containing poly (&#949;-caprolactone) (PCL) nanofibers (i.e., PCL/keratin composite fiber). Water soluble keratin was first extracted from human hair and mixed with PCL in different ratios. The blended solution of PCL/keratin was transformed into nanofibrous membranes using a laboratory designed electrospinning set up. Fiber morphology and mechanical properties of the obtained nanofiber were observed and measured using scanning electron microscopy and tensile tester. Furthermore, degradability and chemical properties of the nanofiber were studied by FTIR. SEM images showed uniform surface morphology for PCL/keratin fibers of different compositions. These PCL/keratin fibers also showed excellent mechanical properties such as Young&#39;s modulus and failure point. Fibroblast cells were able to attach and proliferate thus proving good cell viability. Based on the characteristics discussed above, we can strongly argue that the blended nanofibers of natural and synthetic polymers can represent an excellent development of composite materials that can be used for different biomedical applications.

Electrospun nanofibers have a high surface area to weight ratio, excellent mechanical integrity, and support cell growth and proliferation. These nanofibers have a wide range of biomedical applications. Here we fabricate keratin/ PCL nanofibers, using the electrospinning technique, and characterize the fibers for possible applications in tissue engineering.

Síntese de nanofibras baseado em queratina de Engenharia Biomédica

Electrospinning, due to its versatility and potential for applications in various fields, is being frequently used to fabricate nanofibers. Production of ...

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices. Similarly, the fundamental need of biomedicine to use sterile tools to avoid potential adverse-side effects, such as toxicity or contamination of the biological environment, gives rise to increasing interest in the microwave-assisted strategy.
The combination of click chemistry and the microwave-assisted method is suitable to produce biocompatible hydrogels with desired functionalities and improved performances in biomedical applications. This work aims to synthesize RGD-functionalized hydrogels. RGD (arginylglycylaspartic acid) is a tripeptide that can mimic cell adhesion proteins and bind to cell-surface receptors, creating a hospitable microenvironment for cells within the 3D polymeric network of the hydrogels. RGD functionalization occurs through Huisgen 1,3-dipolar cycloaddition. Some PAA carboxyl groups are modified with an alkyne moiety, whereas RGD is functionalized with azido acid as the terminal residue of the peptide sequence. Finally, both products are used in a copper catalyzed click reaction to permanently link the peptide to PAA. This modified polymer is used with carbomer, agarose and polyethylene glycol (PEG) to synthesize a hydrogel matrix. The 3D structure is formed due to an esterification reaction involving carboxyl groups from PAA and carbomer and hydroxyl groups from agarose and PEG through microwave-assisted polycondensation. The efficiency of the gelation mechanism ensures a high degree of RGD functionalization. In addition, the procedure to load therapeutic compounds or biological tools within this functionalized network is very simple and reproducible.

We present a protocol for the synthesis of RGD-functionalized hydrogels as devices for cell and drug delivery. The procedure involves copper catalyzed alkyne-azide cycloaddition (CuAAC) between alkyne-modified polyacrylic acid (PAA) and a RGD-azide derivative. The hydrogels are formed using microwave-assisted polycondensation and their physicochemical properties are investigated.

A Síntese de hidrogéis RGD-funcionalizado como uma ferramenta para aplicações terapêuticas

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and ...

Polydimethylsiloxane-polycarbonate Microfluidic Devices for Cell Migration Studies Under Perpendicular Chemical and Oxygen Gradients

This paper reports a microfluidic device made of polydimethylsiloxane (PDMS) with an embedded polycarbonate (PC) thin film to study cell migration under combinations of chemical and oxygen gradients. Both chemical and oxygen gradients can greatly affect cell migration in vivo; however, due to technical limitations, very little research has been performed to investigate their effects in vitro. The device developed in this research takes advantage of a series of serpentine-shaped channels to generate the desired chemical gradients and exploits a spatially confined chemical reaction method for oxygen gradient generation. The directions of the chemical and oxygen gradients are perpendicular to each other to enable straightforward migration result interpretation. In order to efficiently generate the oxygen gradients with minimal chemical consumption, the embedded PC thin film is utilized as a gas diffusion barrier. The developed microfluidic device can be actuated by syringe pumps and placed into a conventional cell incubator during cell migration experiments to allow for setup simplification and optimized cell culture conditions. In cell experiments, we used the device to study migrations of adenocarcinomic human alveolar basal epithelial cells, A549, under combinations of chemokine (stromal cell-derived factor, SDF-1&#945;) and oxygen gradients. The experimental results show that the device can stably generate perpendicular chemokine and oxygen gradients and is compatible with cells. The migration study results indicate that oxygen gradients may play an essential role in guiding cell migration, and cellular behavior under combinations of gradients cannot be predicted from those under single gradients. The device provides a powerful and practical tool for researchers to study interactions between chemical and oxygen gradients in cell culture, which can promote better cell migration studies in more in vivo-like microenvironments.

The control of chemical and oxygen gradients is essential for cell cultures. This paper reports a polydimethylsiloxane-polycarbonate (PDMS-PC) microfluidic device capable of reliably generating combinations of chemical and oxygen gradients for cell migration studies, which can be practically utilized in biological labs without sophisticated instrumentation.

Polidimetilsiloxano-policarbonato microfluídicos para celular Estudos Migratórios Sob Perpendicular Chemical e gradientes de oxigênio

This paper reports a microfluidic device made of polydimethylsiloxane (PDMS) with an embedded polycarbonate (PC) thin film to study cell migration under ...

Synthesis of Hydrogels with Antifouling Properties As Membranes for Water Purification

Hydrogels have been widely utilized to enhance the surface hydrophilicity of membranes for water purification, increasing the antifouling properties and thus achieving stable water permeability through membranes over time. Here, we report a facile method to prepare hydrogels based on zwitterions for membrane applications. Freestanding films can be prepared from sulfobetaine methacrylate (SBMA) with a crosslinker of poly(ethylene glycol) diacrylate (PEGDA) via photopolymerization. The hydrogels can also be prepared by impregnation into hydrophobic porous supports to enhance the mechanical strength. These films can be characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) to determine the degree of conversion of the (meth)acrylate groups, using goniometers for hydrophilicity and differential scanning calorimetry (DSC) for polymer chain dynamics. We also report protocols to determine the water permeability in dead-end filtration systems and the effect of foulants (bovine serum albumin, BSA) on membrane performance.

This paper reports practical methods to prepare hydrogels in freestanding films and impregnated membranes and to characterize their physical properties, including water transport properties.

Síntese de hidrogeles com propriedades anti-deposição como membranas de purificação de água

Hydrogels have been widely utilized to enhance the surface hydrophilicity of membranes for water purification, increasing the antifouling properties and ...

Ammonia Synthesis at Low Pressure

Ammonia can be synthesized at low pressure by the use of an ammonia selective absorbent. The process can be driven with wind energy, available locally in areas requiring ammonia for synthetic fertilizer. Such wind energy is often called &#34;stranded,&#34; because it is only available far from population centers where it can be directly used.
In the proposed low pressure process, nitrogen is made from air using pressure swing absorption, and hydrogen is produced by electrolysis of water. While these gases can react at approximately 400 &#176;C in the presence of a promoted conventional catalyst, the conversion is often limited by the reverse reaction, which makes this reaction only feasible at high pressures. This limitation can be removed by absorption on an ammine-like calcium or magnesium chloride. Such alkaline metal halides can effectively remove ammonia, thus suppressing the equilibrium constraints of the reaction. In the proposed absorption-enhanced ammonia synthesis process, the rate of reaction may then be controlled not by the chemical kinetics nor the absorption rates, but by the rate of the recycle of unreacted gases. The results compare favorably with ammonia made from a conventional small scale Haber-Bosch process.

Ammonia can be synthesized at low pressure by using a conventional catalyst and an ammonia selective absorbent.

Síntese de amônia a baixa pressão

Ammonia can be synthesized at low pressure by the use of an ammonia selective absorbent. The process can be driven with wind energy, available locally in ...

Synthesis of Functionalized 10-nm Polymer-coated Gold Particles for Endothelium Targeting and Drug Delivery

Gold nanoparticles (AuNPs) have been used extensively in medical research due to their size, biocompatibility, and modifiable surface. Specific targeting and drug delivery are some of the applications of these AuNPs, but endothelial extracellular matrices&#39; defensive properties hamper particle uptake. To address this issue, we describe a synthesis method for ultrasmall gold nanoparticles to improve vascular delivery, with customizable functional groups and polymer lengths for further adjustments. The protocol yields 2.5 nm AuNPs that are capped with tetrakis(hydroxymethyl)phosphonium chloride (THPC). The replacement of THPC with hetero-functional polyethylene glycol (PEG) on the surface of the AuNP increases the hydrodynamic radius to 10.5 nm while providing various functional groups on the surface. The last part of the protocol includes an optional addition of a fluorophore to allow the AuNPs to be visualized under fluorescence to track nanoparticle uptake. Dialysis and lyophilization were used to purify and isolate the AuNPs. These fluorescent nanoparticles can be visualized in both in vitro and in vivo experiments due to the biocompatible PEG coating and fluorescent probes. Additionally, the size range of these nanoparticles render them an ideal candidate for probing the glycocalyx without disrupting normal vasculature function, which may lead to improved delivery and therapeutics.

We describe a method of synthesizing biocompatible 10-nm gold nanoparticles, functionalized by coating poly-ethylene glycol onto the surface. These particles can be used in vitro and in vivo for delivering therapeutics to nanoscale cellular and extracellular spaces that are difficult to access with conventional nanoparticle sizes.

Síntese de funcionalizados 10 nm polímero-revestida com partículas de ouro para o direcionamento do endotélio e entrega da droga

Gold nanoparticles (AuNPs) have been used extensively in medical research due to their size, biocompatibility, and modifiable surface. Specific targeting ...