이 연구 작업은 원자 수준의 촉매 디자인, 미국 에너지 부, 과학, 보너스 번호 DE-SC0001058에서 기초 에너지 과학 국의 재정 지원 에너지 프론티어 연구 센터의 센터의 한 부분으로 지원하고 또한 이사회에 의해 지원됩니다 부여 보너스 번호 LEQSF (2009-14) EFRC-MATCH와 LEDSF-EPS (2012)-OPT-IN-15에서 리전트. MRCAT 작업은 에너지 부와 MRCAT 회원 기관에 의해 지원된다. ANL에서 고급 광자 소스의 사용은 계약 번호 DE-AC02-06CH11357에서 미국 에너지 부, 과학, 기초 에너지 과학의 사무실의 사무실에 의해 지원됩니다. JTM에 대한 재정 지원은 아톰 효율적인 화학 변환에 대한 연구소 (IACT), 미국 에너지 부에 의해 투자 에너지 프론티어 연구 센터, 과학의 사무실, 기초 에너지 과학의 사무실의 일부로 제공되었다.

Millifluidics 세트 - 최대 : 220mm (L) × 2mm (W) X 0.15 mm (H)의 크기와 뱀 채널이 Microplumbers Microsciences LLC에서 (폴리 에스테르 테레 프탈레이트 폴리머로 제작) millifluidic 칩을 구입하실 수 있습니다. 펌프에 칩을 연결하는 0.25 mm의 ID의 크기, OD 1 / 16로 FEP 튜브를 사용합니다. 두 개의 서로 다른 실험을 위해 두 개의 서로 다른 펌프를 사용합니다. 첫 번째 실험 (구리 나노 입자)와 두 번째 실험 (금 나노 입자)의 millifluidic 장치를 사용하여 P-펌프. , 채널 내에서 가스 버블의 문제점을 최소화하기 위해 새로 제조에 NaBH 4 용액을 기체 기포가 용액으로부터 벗어날 수 있도록 칩에 펌핑하기 전에 10-15 분간 ~ 동안 정치 개방 하였다. 이 단계는 실험의 모든 하였다. 1. 매우 작은 구리 나노 클러스터 (UCNCs)의 합성 <ol><li> 필요한 화학 물질 : 구리를 얻습니다 (II) 니트라TE 수화물, 수소화 붕소 나트륨, 수산화 나트륨 펠렛 및 O-[2 - (3 - mercaptopropionylamino) 에틸]-O&#39;-methylpolyethylene 글리콜 (MW = 5000) [MPEG]을 더 정제하지 않고 모든 화학 물질을 사용한다. 실험 nanopure 물 (18.2 MΩ-cm)를 사용합니다. </li><li> 사용 P-펌프 실험 질소 압력 하에서 규제. 해당 흐름 속도 (㎖ / 시간)와 연관시키는 실험 전에 다른 압력에서 용매로 물을 펌프를 테스트합니다. 실험을 시작하기 전에 탈 이온수로 millifluidic 반응기 튜브를 씻어. </li><li> 구리의 174 밀리그램 (0.95 밀리몰)을 녹이고, (II) 질산 및 O-[2 - (3 - mercaptopropionylamino) 에틸] 610 밀리그램 (0.122 mmol)을에-O&#39;-methylpolyethylene의 nanopure 물 28 ㎖의에 글리콜, 계속 그 하나의 입력 채널에 연결하기 바이알 </li><li> 다른 바이알에 다른 수소화 붕소 나트륨 111 mg을 용액 (2.93 mmol) 및 102 mg의 (2.78 mmol)을 28 ㎖ 중의 수산화 나트륨 (약 pH 13)을 유지하고 그것을 연결다른 입력 채널. </li><li> 다른 흐름 속도 (아래)에서 millifluidic 반응기 내에서 동시에 솔루션 흐름과 유리 병에있는 출구에서 결과 UCNCs를 수집합니다. 질소를 용액을 제거하고, 질소하에 저장한다. </li><li> 의 합성 상온에서 50 밀리바 (6.81 ㎖ / 시간), 100 밀리바 (14.31 ㎖ / 시간), 200 밀리바 (32.7 ㎖ / 시간) 300 밀리바 (51.4 밀리리터 / 시간)의 다른 일정 압력에서 펌프를 작동 다른 흐름 속도로 UCNCs. </li></ol> 합성 절차가 P-펌프가 millifluidic 셋업을 사용하여 설명되었지만, 그것은 또한 Millifluidica로부터 휴대용 millifluidic 장치를 사용하여 수행 될 수있다. 2. 시간은 금 나노 입자의 형성에 현장 운동 연구에서 해결 <ol><li> 필요한 화학 물질 : 염화 금산 (. HAuCl 4 3H 2 O) 메소 -2,3 - dimercaptosuccinic 산 (DMSA)와 소듐 보로 하이드 라이드 &amp; # 받기(160)와, 추가의 정제없이 모든 화학 물질을 사용한다. 실험 nanopure 물 (18.2 MΩ-cm)를 사용합니다. </li><li> 완전 자동화, 맥동 무료 주사기 펌프는 칩 내의 액체 흐름, 높은 정밀도를 사용합니다. 필요한 유량을 최적화하기 위해 실험 전에 다른 흐름 속도로 용매로 물을 펌프를 테스트합니다. </li><li> (I) HAuCl 4의 표준 용액을 준비합니다. 3H 2 O (10 밀리몰, 118.2 mg/30 ml)에 nanopure 수산화 나트륨 (산도 12)의 50 밀리그램 (II) DMSA (20 밀리몰, 109.2 mg/30 ml)을 물. </li><li> 자동 펌프를 이용하여 10 ㎖ / hr의 일정한 유량에서 millifluidic 칩에 두 개의 별도의 주사기를 통해 두 용액을 피드. </li><li> 커플 XYZ 방향으로의 이동에 대한 액세스를 가지며 해법은 칩을 통해 펌핑 하였다로서 칩에 다른 시간대에 XAS 데이터를 수집 금속 스테이지를 사용 싱크로트론 빔 라인에 millifluidic 칩. </li></ol> &lt;동안EM&gt; 시츄 분석 절차는 P-펌프가 millifluidic 셋업을 사용하여 입증되었고, 또한 휴대용 millifluidic 장치를 사용하여 수행 될 수있다. 3. 연속 흐름 금 촉매 이 절차는 핸드 헬드 장치를 사용 millifluidic 입증되었다. <ol><li> 필수 화학 물질 : 염화 금산 (. HAuCl 4 3H 2 O), 메소 -2,3 - dimercaptosuccinic 산 (DMSA), 수소화 붕소 나트륨, 4 - 니트로 페놀, 4 - 아미노 페놀을 구하여이를 추가적인 정제없이 모든 화학 물질을 사용한다. 실험 nanopure 물 (18.2 MΩ-cm)를 사용합니다. </li><li> 촉매 제조 :. HAuCl 4의 표준 용액을 준비 3H 2 O Nanopure (10 밀리몰, 118.2 mg/30 ml)에 DMSA (20 밀리몰, 109.2 mg/30 ㎖)의 NaBH 4 (10 밀리몰, 11.34 mg/30 ml)을 물. </li><li> 두 개의 유리 병에 HAuCl 4 DMSA 솔루션 10 ㎖를 각각 가지고 일을 흐름45 분 동안 12 ㎖ / hr의 일정한 유속으로 소형 millifluidic 장치를 이용하여 칩 내의 EM. </li><li> 오에 오 (I)를 줄이기 위해 15 분 동안 12 ㎖ / 시간의 흐름 속도로 칩 내에서 10 밀리몰의 NaBH 4 흐름 (0). </li><li> 마지막으로, 촉매 반응 실험을 수행하기 전에 동일한 유량에서 30 분 동안 nanopure 물과 칩을 씻어. </li><li> 촉매 반응 : 아래로 금 촉매 (상기에서 제조) 내에서 4 - 아미노 페놀 (4-AP)에 4 - 니트로 페놀의 화학적 전환 반응 (환원) (4-NP)을 수행은 millifluidic 채널을 입혔다. </li><li> 4 nitrophenolate 이온 (4-NPI)를 형성하기 위해 0.65 몰의 NaBH 4 용액을 3.3 ㎖로 4-NP의 9 × 10 -5 몰 용액 15 ㎖를 혼합한다. </li><li> 촉매 활성을 평가하기 위해 5 ㎖ / hr의 일정한 유량에서 칩 내에 증착 금 촉매를 통해 얻어진 용액을 합격. 250-50의 파장 범위 내에서 수집 된 제품의 UV-VIS 스펙트럼을 분석0 nm의 4-NP의 전환을 확인합니다. </li><li> 4 - NPI의 검량선을 얻음으로써, 반응의 촉매 활성을 추정한다. 검량선 다른 표준 농도 4 NPI의 실험적 관찰 흡수 강도 (I을) 플롯에 의해 획득 될 수있다. UV-VIS 흡수 커브 (399 nm에서)의 피크 높이가 흡수 강도 (I)의 값을 나타내고, 비어 램버트의 법칙에 따라, 피크 높이 값의 변화가 그 농도에 대응하는 변화를 보여줄 것이다. 따라서, 검량선으로부터 반응물의 초기 및 최종 농도에 차이를 발견함에 따라 촉매 활성을 추정한다. 피크 높이가 1 단위 (도 6) 인 경우 예를 들어, (캘리브레이션 플롯 기준) 90 %의 촉매 전환에 상당한다. </li></ol>

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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>

CSSR 쿠마를 제외한 모든 저자는 더 경쟁 재정적 이익이 없다는 것을 선언합니다. C. SSR 쿠마 회사 Millifluidica LLC의 설립자이다.

-O&#39;-methylpolyethylene 글리콜 (MW = 5000) [MPEG] - UCNCs는 중합체 캐핑 에이전트 O-[(3 - Mercaptopropionylamino) 에틸 2]의 존재하에 수소화 붕소 나트륨과 질산 구리의 환원 반응에 의해 형성 하였다. 반응은 6.8 ㎖ / 시간, 36.3 ㎖ / 시간, 32.7 ㎖ / 시간 및 형성 UCNCs에 흐름 비율의 효과를 연구하기 위해 51.4 ㎖ / 시간으로 다른 흐름 속도로 millifluidic 칩 반응기 내에서 수행 하였다. 위의 흐름 속도에 대한 각각의 체?...

화학 합성 실험실 - 온 - 칩 (LOC) 장치가 증가 질량과 열전달, 뛰어난 반응 제어, 높은 처리량 및 안전한 작업 환경 (1)의 측면에서 상당한 이점을 증명하고있다. 이러한 장치는 광범위 칩 기반의 유체와 nonchip 기반 유체 소자로 분류 될 수있다. 칩 기반의 유체 사이에서, 마이크로 유체 잘 조사하고, 주제는 문학 2-5에서 잘 덮여. Nonchip 기반 LOC 시스템은 관형 반응기 (6)를 사용합니다. 통상적으로, 마이크로 유체 시스템은 정확한 컨트롤과 기하학적 서브 밀리미터 규모로 제한하는 유체의 조작에 사용됩니다. 우리는 최근 (폭 또는 깊이 또는 채널의 양쪽 모두는 크기가 최소 mm이다) 7-9 밀리미터 스케일 채널에서 유체의 조작을 위해 사용될 수있다 칩 기반 millifluidics의 개념을 도입 하였다. 또한, millifluidic 칩은 WHI를 제조하기가 비교적 쉽다르 흐름 속도 및 시약의 조작을 제어하기위한 비슷한 방법을 제공합니다. 이 칩은 좁은 크기 분포를 갖는 나노 입자의 제어 합성의 스케일 업에 대한 가능성을 제공함으로써, 작은 체류 시간을 만들고, 높은 흐름 속도로 작동 할 수 있습니다. 예를 들어, 우리는 최근 초소형 구리 나노 클러스터의 합성을 시연하고 현장 X-선 흡수 분광법에 사용뿐만 아니라 TEM을 특징으로했다. 구리 나노 클러스터 (7)의 안정된 콜로이드의 형성에 매우 효율적 두자리 PEG 화 안정 화제입니다 MPEG의 사용과 함께 millifluidic 채널 내에서 작은 체류 시간을 얻을 수있는 능력. 화학 물질과 나노 물질의 합성뿐만 아니라, millifluidics 때문에 프로브 영역에서 높은 양 및 농도, 더 일반화하고 효율적인 시간 분해 동역학 연구도 achie이다 합성 플랫폼에 제공 할마이크로 유체 시스템 7,10보다 노이즈 비율로 신호가 잘 보이는 군. 우리는 5 밀리 초 (11)와 같은 작은 시간 해상도와 동일계 XAS에서 사용한 용액으로부터 금 나노 구조물의 성장 시간이 해결 분석을위한 예로서 millifluidic 칩의 사용을 보여준다. 또한, 촉매 응용 프로그램에 대한 최신 개발 된 마이크로 반응기의 대부분은 실리콘 (12, 13)를 기준으로합니다. 생성 된 작은 볼륨뿐만 아니라 고가의 제조는 대규모 제조되지는 않습니다. 나노 촉매와 채널 코팅하는 두 가지 일반적인 방법 - 화학적 및 물리적 종종 실리콘 코팅 절차 칭함 보그 14,15 현재이다. 고가의 마이크로 제조 외에도 채널의 막힘은 마이크로 반응기의 촉매가 대규모 생산에 부적합하게 될 수있다. 마이크로 반응기는 마이크로 연속 관류 공정의 earli 이종 촉매에 사용되었지만16-18 어, 치수를 제어 할 수있는 능력, 지속적인 흐름 채널에 내장 된 금 나노 촉매의 형태는 이전에 탐험되지 않았습니다. 우리는 최근의 Au 촉매와 millifluidic 채널을 코팅하는 기술을 개발 한 나노 형태와 치수 (그림 5) (11)를 제어하는 데, 산업적으로 중요한 화학 반응의 촉매 작용을 수행하기위한. 예를 들어 우리는 millifluidic 채널 내에서 코팅 된 나노 금 촉매로 4 - 아미노 페놀에 4 - 니트로 페놀의 변환을 증명하고있다. 단일 millifluidic 반응 칩이 50 ~ 60 ㎖ / 시간, 7 높은 처리량 및 화학 물질의 제어 합성의 흐름 속도를 생성 할 수 있음을 감안하면 어느 연속 흐름 작업 또는 병렬 처리를 통해 가능하다. millifluidics 이상으로 설명 몇 가지 예제와 함께 제공하는 가능성을 활용하기 위해, 우리는 또한 보여 사용자 친화적 인이식하고있다 millifluidic 장치는 millifluidic 칩, 매니 폴드, 유동 제어기, 펌프 및 전기적 연결과 같은 모든 필요한 구성 요소가 통합. 이러한 millifluidic 장치는,도 7에 도시 된 바와 같이, 지금의 회사 Millifluidica LLC (에서 구할 <a href="http://www.millifluidica.com" target="_blank">www.millifluidica.com</a> ). 원고는 나노 물질, 반응 메커니즘과 연속 유동 촉매의 시간 분해 분석 제어 합성에 대해, 후술하는 바와 같이, 핸드 헬드 장치를 사용 millifluidic 프로토콜을 제공한다.

<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

화학 합성 시간이 해결 기계론의 연구에 대한 millifluidic 장치를 이용하는 절차는 세 가지 예를 복용에 의해 설명되어 있습니다. 먼저, 초소형 구리 나노 클러스터의 합성은 설명한다. 두 번째 예는 현장 X-선 흡수 분광법에 사용하는 금 나노 입자의 형성을 분석하여 화학 반응의 시간이 해결 된 역학 조사에 대한 자신의 유틸리티를 제공합니다. 마지막 예제는 나노 구조 촉매로 코팅 millifluidic 채널 내부 반응의 연속적인 흐름의 촉매 작용을 보여줍니다.

잘 분산 및 좁은 크기 분포를 갖는 균일 한 크기의 구리 나노 클러스터는 millifluidic 칩 설정 (도 1A)를 사용하여 수득 하였다. 합성을 위해 사용되는 상이한 흐름 속도는 클러스터의 크기에 유의 한 영향을 미치지 않았다. 그럼에도 불구하고, 유속의 증가와 함께, 크기 분포의 축소에 관찰 가능한 개선이있다. 유용한 좁은 크기 분포를 갖는 UCNCs은 32.7 ㎖ / hr의 유량으로 얻었다. 32.7 ㎖ / 시간의 유량?...

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 장치는 나노 물질, 반응 메커니즘과 지속적인 흐름 촉매의 시간 분해 분석의 제어 합성에 이용된다.

화학 합성 및 시간 - 해결 기계론의 연구 Millifluidics

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

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11.1K 조회수.  Louisiana State University.  Millifluidic 장치는 나노 물질, 반응 메커니즘과 지속적인 흐름 촉매의 시간 분해 분석의 제어 합성에 이용된다. 

비디오: 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.

조합의 합성과 고분자 필름과 Nanoparticle 도서관에서 높은 처리량 단백질 출시

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

연구

생체공학

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.

Polyanhydride의 Nanoparticles의 높은 처리량 탄수화물의 합성과 작용화

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.

세포 물질의 상호 작용 연구를위한 나노 기공 골드 패턴의 미세

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.

테인 매개 인공 단백질 히드로 겔의 합성

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.

의 생명 공학에 대한 각질 기반의 나노 섬유의 합성

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.

치료 응용 프로그램을위한 도구로 RGD-작용 히드로 겔의 합성

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.

셀 마이그레이션 연구에서 수직 화학 산소 그라디언트에 대한 폴리 디메틸 실록산 - 폴리 카보네이트 미세 유체 장치

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.

물 정화를위한 막으로 방오 특성을 가진 히드로 겔의 합성

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.

저압에서 암모니아 합성

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.

기능성된 10 nm 폴리머-코팅 된 금 입자 피 대상에 대 한 및 약물 전달의 합성

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