Financial support provided by National Science Foundation (CAREER award CHE-0847262. We thank Vapourtec Ltd and Enwave Optronics for equipment support, and Daniel Daleb of the University of Connecticut for his assistance in construction of the flow cell apparatus.

1.查找反应监测合适信号。 <ol><li>获得的拉曼光谱对所有的起始原料和产物。 </li><li>叠加光谱并确定一个强烈频带是唯一的产物。 </li><li>使用该拉曼频带以监测反应的进度。在1608厘米的带-1在这种情况下被选中。 </li></ol> 2.设置流动池<ol><li>获得合适的流动池。这里使用一个具有以下尺寸：宽度为6.5毫米，20毫米的高度，并且为5毫米（图2A）的路径长度。 </li><li>将流动池的容器中，提供了一个自由的环境光的环境中。 </li><li>连接管道到流动池的入口和出口（在此情况下1毫米的ID的PFA管）。 </li></ol> 3.接口拉曼光谱仪的流动池<ol><li>获得合适的拉曼光谱仪与柔性光学组件，其可以放置在C失去接近流通池。 </li><li>通过在含有流动池装置（图2B）的框合适尺寸的孔放置光学组件。 </li><li>光学组件滑动，直到它触及流动池，然后将它拉回来留下〜2毫米的间隙。 </li><li>填用100％丙酮流动池。 </li><li>打开拉曼光谱仪，并获得谱在连续扫描模式。 </li><li>通过一次轻轻移动所述光管的一部分聚焦激光。保持移动光管，直到信号处于其最大的强度和峰尖锐且明显。 </li></ol><img alt="图2" src="/files/ftp_upload/52393/52393fig2.jpg" /> 图2.（A）流动池，并用（B）拉曼接口。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig2large.jpg" target="_blank">请点击此处查看大图已经</a>rsion这个数字。 4.准备试剂和溶剂溶液<ol><li>添加水杨醛（六点一〇六克，50毫摩尔，1当量）和乙酰乙酸乙酯（6.507克，50毫摩尔，1当量）到50ml容量瓶中。 </li><li>加入乙酸乙酯至50毫升的总体积，然后彻底混合内容。 </li><li>转移10ml的等分试样原液含有磁性搅拌棒的20ml玻璃小瓶中。标签此瓶“试剂”。 </li><li>在100毫升的瓶代替90毫升乙酸乙酯。标签这瓶“溶剂”。在100毫升一瓶的地方90毫升丙酮。标签这瓶“溶剂拦截”。 </li></ol> 5.准备流动设备的<ol><li>确保该流动单元具有至少两个泵和标签他们“P1”和“P2”。确定每个泵溶剂和试剂入口线。将在“收”和“废物”生产线出口线路分成两个我，ndividual100毫升瓶标有“产品”和“浪费”分别。 </li><li>作为反应器，用10毫升容量PFA线圈能够被加热的。 </li><li>管排出P1连接到PFA反应器盘管的入口。 </li><li>电感线圈后，安装一个三端口聚醚醚酮（PEEK）发球混合器。 </li><li>管排出的P2连接到T型混合器，从反应器中线圈的出口管道180°。一管件连接到三通混频器的第三端口。在此管的另一端放置一个背压调节器。 </li><li>从回压调节到流通池的输入输出端连接的线。从流动池的输出线连接到“废/收集”开关。 </li><li>素的溶剂线为P1和P2以及为P1中的试剂线用溶剂。从溶剂瓶的试剂瓶移动试剂线P1上。 </li><li>利用P1，通过反应器通过乙酸乙酯线圈在2毫升/分钟，直到它被充满。至P2通过丙酮以2ml /分的流速分钟2分钟。 </li><li>调节溶剂的流速为P1和P2，以1毫升/分钟。设置回压调节到7巴的压力下。设置在反应器线圈温度到所需的温度。 </li><li>仔细检查设备被配置为图 3所示的原理图。 </li><li>一旦系统达到恒定的温度和压力，检查是否漏水，然后运行反应。 </li></ol><img alt="图3" src="/files/ftp_upload/52393/52393fig3.jpg" /> 图3.原理用于反应监测实验设备的配置。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 6.监控反应<ol><li>德的乙酸乙酯/丙酮溶剂体系EA后台扫描因为它通过流动池。这将从所有后续的扫描自动扣除。 </li><li>配置分光计采取扫描每15秒（在此情况下，拉曼光谱仪被设定为10秒的积分时间，棚车= 3，平均值= 1）。 </li><li>注射哌啶（0.05毫升，0.05毫摩尔，0.1当量）一次全部进入标有“试剂”的玻璃小瓶。 </li><li>从后充分混合，开关P1“溶剂”到“试剂”将退出流“收集”。 </li><li>当所有材料完全加载从“试剂”，切换P1回“溶剂”。继续通过电感线圈另外30分钟流淌的溶剂。一旦超过这个时间，关掉暖气。 </li><li>转泵P1和P2时关闭反应器线圈温度已冷却至低于50℃。 </li></ol> 7.分析数据<ol&gt; <li>在拉曼光谱仪的数据导出到电子表格和情节拉曼强度1608厘米-1主场迎战时间。 </li><li>为了优化的条件下，进行跨越多个流速和反应器温度的以迭代的方式进行反应。 </li><li>叠加图拉曼强度的1608厘米-1主场迎战时间。 注：更高的拉曼强度与较高的产品转化。 </li></ol> 8.运行反应使用优化的条件<ol><li>有筛选各种条件（不同的流速/反应器温度），运行使用优化的条件下，得到最高的产品转化的反应。 </li></ol> 9.隔离产品<ol><li>取产物烧瓶的内容，并将其倒入含有100毫升冰水和20毫升的2M的HCl的烧杯中。 </li><li>冲洗产物烧瓶用乙酸乙酯（2ml）中，并转移到烧杯最小量。 </li><li>搅拌冰冷混合物直到所有的冰完全融化。 </li><li>设置一个过滤系统，具有赫希漏斗，侧臂烧瓶中，橡胶圈和橡胶真空管的长度。 </li><li>过滤所得沉淀在真空下，冲洗用冷乙醚（10ml）中，并允许它在热灯下（2-3小时）或干燥O / N在真空下干燥。 </li><li>确认产品的通过 1 H核磁共振（NMR）波谱使用为 CDCl 3溶剂的身份。为500MHz的NMR波谱仪，是3-乙酰基香豆素的1 H NMR数据如下：δ= 2.73（S，3H）7.31 - 7.40（米，2H）7.65（DDD，J = 7.53，4.37，2.60 Hz的，2H）8.51（S，1H）ppm的，13 C NMR数据;δ= 30.84（CH 3）117.00（CH）118.56（C）的124.86（CH）125.27（CH）130.51（CH）134.68（C）的147.74 （CH），155.64（C）159.52（C）195.77（C）PPM。 </li></ol>

<ol>
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The authors have nothing to disclose.

在该拉曼光谱仪可以与流动单元被接口易于使这一直列技术反应监测有价值。一些反应变量可以探测在加速方式，允许用户在优化的反应条件下使用脱机方法时，速度比到达。本文所述也技术应用允许监视的副产物的形成的，假设一个合适的带都可以找到。条件可筛选和选择，这使得既为最高的转换产物，并​​还杂质的最低量。反应的定量监测也是可能的。由于拉曼信号强度与浓度成正比，校?...

通过采用连续流动加工，化学家们发现他们可以执行一系列的化学反应，安全，高效，轻松，1,2。其结果是，流动化学设备正在成为在学术机构同时运行在工业设置的反应以及研究实验室的整工具。各种各样的合成化学转化已进行了在流反应器3,4。在选择的情况下，反应不以间歇工作已显示出平滑连续流动条件下5继续。对于这两种反应优化和质量控制，串联反应监测与流处理的掺入提供显著优点。在在线监​​测提供连续的分析与实时响应，以实际样品条件。这是更快的，并且在一些情况下，比同类的离线技术更可靠。若干的在线分析技术已接口和f低电抗器7。实施例包括红外8,9，紫外可见10,11，12,13核磁共振，拉曼光谱14,15，和质谱16,17。 我们的研究小组接口拉曼光谱仪用科学的微波单元18。使用此，一系列的反应已经从监测都有了质19和定量的20立场。在此基础上的成功，我们最近接口我们的拉曼光谱仪与我们的连续流单元中的一个，并采用它用于线反应的一个数字键医药相关的有机转化的监视。21在每种情况下，有可能监视反应以及在一个实例中，由校准曲线的装置，我们可以判断从拉曼光谱数据产品转化。在这里，我们介绍如何设置设备，并用它来监视反应。我们使用的哌啶催化的合成的3 - 交流etylcoumarin（1）从水杨醛与乙酰乙酸乙酯（图1）作为此处的模型反应。 <img alt="图1" src="/files/ftp_upload/52393/52393fig1.jpg" /> 图1.碱催化水杨醛与乙酰乙酸乙酯的缩合反应，得到3-乙酰基香豆素（1）。 <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

<table border="0">
	<tbody>
		<tr>
			<td>Salicylaldehyde</td>
			<td>Sigma-Aldrich</td>
			<td>S356</td>
			<td>Reagent Grade, 98%</td>
		</tr>
		<tr>
			<td>Ethyl acetoacetate</td>
			<td>Acros Organics</td>
			<td>117970010</td>
			<td>99%</td>
		</tr>
		<tr>
			<td>Piperidine</td>
			<td>Sigma-Aldrich</td>
			<td>104094</td>
			<td>Reagent Plus, 99%</td>
		</tr>
		<tr>
			<td>Hydrochloric acid</td>
			<td>Sigma-Aldrich</td>
			<td>320331</td>
			<td>ACS Reagent, 37%</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Sigma-Aldrich</td>
			<td>34858</td>
			<td>CHROMASOLV, for HPLC, &#62;99.7%</td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>Sigma-Aldrich</td>
			<td>650501</td>
			<td>CHROMASOLV, for HPLC, &#62;99.9%</td>
		</tr>
		<tr>
			<td>Flow cell</td>
			<td>Starna Cells</td>
			<td></td>
			<td>583.65.65-Q-5/Z20</td>
		</tr>
		<tr>
			<td>Flow unit</td>
			<td>Vapourtec</td>
			<td></td>
			<td>E-series system</td>
		</tr>
		<tr>
			<td>Raman spectrometer</td>
			<td>Enwave Optronics Inc</td>
			<td></td>
			<td>Model EZRaman-L</td>
		</tr>
	</tbody>
</table>

real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example

通过使用内嵌的监测，可以优化以简单和快速的方式使用连续流动处理进行的反应。另外，也可以确保在一段时间一致的产品质量使用这种技术。我们在这里显示了如何用拉曼光谱仪接口的市售流动单元。拉曼流动池被放置在回压调节器后，这意味着它可以在大气压力下操作。此外，该产品流通过管道进入流动池之前的长度的事实意味着该材料是在室温下。重要的是，该光谱等温条件下获得的，因为拉曼信号强度取决于温度。具有组装的装置中，我们然后显示如何监视一个化学反应中，哌啶催化的合成将3-乙酰基香豆素从水杨醛和乙酰乙酸乙酯被用作一个例子。该反应可以在一定范围的流率的执行Ð的温度下， 在现场监测工具被用于简单而容易地优化条件。

连续流动制备3-乙酰基香豆素被选定为在在线监测一个代表反应。在分批，反应进行很好，使用乙酸乙酯作为溶剂时。然而，产物（1）是不完全溶解在RT。为了防止回压调节器的潜在的堵塞，以及减轻在流动池这会扰乱信号采集具有固体颗粒的风险，我们使用了我们先前开发针对此等反应22技术。我们将反应线圈用丙酮后截获产品流以溶解产物，并允许它穿过流动池和背压调?...

Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

实时监控允许使用连续流动处理进行的反应的快速优化。这里的3-乙酰基香豆素，制剂被用作示例。用于进行原位拉曼监测装置进行说明，因为都是以优化反应所需的步骤。

反应执行使用连续流处理的实时监控：3  - 乙酰基香豆素的制备为例

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible ...

real-time-monitoring-reactions-performed-using-continuous-flow

Research

JoVE Journal

Chemistry

9.6K 次观看.  University of Connecticut. 实时监控允许使用连续流动处理进行的反应的快速优化。这里的3-乙酰基香豆素，制剂被用作示例。用于进行原位拉曼监测装置进行说明，因为都是以优化反应所需的步骤。 

视频: Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

A method for species identification of botanical material by direct analysis in real time-high resolution mass spectrometry and multivariate statistical analysis is presented.

植物材料的快速高通量物种鉴定实时高分辨质谱法直接分析

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, ...

科研

化学

Capillary Electrophoresis to Monitor Peptide Grafting onto Chitosan Films in Real Time

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. Compared to other analytical separation techniques, such as chromatography, CE is cheap, robust and effectively requires no sample preparation (for a number of complex natural matrices or polymeric samples). CE is fast and can be used to follow the evolution of mixtures in real time (e.g., chemical reaction kinetics), as the signals observed for the separated compounds are directly proportional to their quantity in solution.
Here, the efficiency of CE is demonstrated for monitoring the covalent grafting of peptides onto chitosan films for subsequent biomedical applications. Chitosan&#39;s antimicrobial and biocompatible properties make it an attractive material for biomedical applications such as cell growth substrates. Covalently grafting the peptide RGDS (arginine - glycine - aspartic acid - serine) onto the surface of chitosan films aims at improving cell attachment. Historically, chromatography and amino acid analysis have been used to provide a direct measurement of the amount of grafted peptide. However, the fast separation and absence of sample preparation provided by CE enables equally accurate yet real-time monitoring of the peptide grafting process. CE is able to separate and quantify the different components of the reaction mixture: the (non-grafted) peptide and the chemical coupling agents. In this way the use of CE results in improved films for downstream applications.
The chitosan films were characterized through solid-state NMR (nuclear magnetic resonance) spectroscopy. This technique is more time-consuming and cannot be applied in real time, but yields a direct measurement of the peptide and thus validates the CE technique.

Free solution capillary electrophoresis is a fast, cheap and robust analytical method that enables the quantitative monitoring of chemical reactions in real time. Its utility for rapid, convenient and precise analysis is demonstrated here through analysis of covalent peptide grafting onto chitosan films for improved cell adhesion.

毛细管电泳监视肽接枝壳聚糖膜实时

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. ...

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.

The safe and proper use of organolithium reagents is described.

使用有机锂试剂的一个协议安全的锂化反应

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

Monitoring the Effects of Illumination on the Structure of Conjugated Polymer Gels Using Neutron Scattering

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and absence of white light exposure. By instituting a controlled temperature ramp, the gelation of these materials can be precisely monitored as they proceed through this structural evolution, which effectively mirrors the conditions experienced during the solution deposition phase of organic electronic device fabrication. Using small angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) along with appropriate fitting protocols we quantify the evolution of select structural parameters throughout this process. Thorough analysis indicates that continued light exposure throughout the gelation process significantly alters the structure of the ultimately formed gel. Specifically, the aggregation process of poly(3-hexylthiophene-2,5-diyl) (P3HT) nano-scale aggregates is negatively affected by the presence of illumination, ultimately resulting in the retardation of growth in conjugated polymer microstructures and the formation of smaller scale macro-aggregate clusters.

A protocol for the analysis of gels formed from the optoelectronic conjugated polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) using small and ultra-small angle neutron scattering in both the presence and absence of illumination is presented.

利用中子散射监测光照对共轭高分子凝胶结构的影响

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and ...

Measurements of Long-range Electronic Correlations During Femtosecond Diffraction Experiments Performed on Nanocrystals of Buckminsterfullerene

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the results of femtosecond X-ray free electron laser (XFEL) experiments. An increasing number of experimental observations have shown that although nuclear motion can be negligible, given a short enough incident pulse duration, electronic motion cannot be ignored. The current and widely accepted models assume that although electrons undergo dynamics driven by interaction with the pulse, their motion could largely be considered &#39;random&#39;. This would then allow the supposedly incoherent contribution from the electronic motion to be treated as a continuous background signal and thus ignored. The original aim of our experiment was to precisely measure the change in intensity of individual Bragg peaks, due to X-ray induced electronic damage in a model system, crystalline C60. Contrary to this expectation, we observed that at the highest X-ray intensities, the electron dynamics in C60 were in fact highly correlated, and over sufficiently long distances that the positions of the Bragg reflections are significantly altered. This paper describes in detail the methods and protocols used for these experiments, which were conducted both at the Linac Coherent Light Source (LCLS) and the Australian Synchrotron (AS) as well as the crystallographic approaches used to analyse the data.

We describe an experiment designed to probe the electronic damage induced in nanocrystals of Buckminsterfullerene (C60) by intense, femtosecond pulses of X-rays. The experiment found that, surprisingly, rather than being stochastic, the X-ray induced electron dynamics in C60 are highly correlated, extending over hundreds of unit cells within the crystals1.

在纳米富勒的飞秒衍射实验的长程电子关联的测量

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the ...

Real-time Breath Analysis by Using Secondary Nanoelectrospray Ionization Coupled to High Resolution Mass Spectrometry

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental exposure in a non-invasive manner. In this work, we present a protocol to characterize the exhaled VOCs in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS). The homemade Sec-nanoESI source was readily set up based on a commercial nanoESI source. Hundreds of peaks were observed in the background-subtracted mass spectra of exhaled breath, and the mass accuracy values are -4.0-13.5 ppm and -20.3-1.3 ppm in the positive and negative ion detection modes, respectively. The peaks were assigned with accurate elemental composition according to the accurate mass and isotopic pattern. Less than 30 s is used for one exhalation measurement, and it takes approximately 7 min for six replicated measurements.

A protocol for characterizing chemical composition of exhaled breath in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry is demonstrated.

利用二次 Nanoelectrospray 电离耦合高分辨质谱的实时呼吸分析

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental ...

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;. Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with &#34;mixing&#34; and &#34;linear&#34; microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology&#39;s competitiveness, sustainability, and versatility in their research.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Flow chemistry carries environmental and economic advantages by leveraging superior mixing, heat transfer and cost benefits. Herein, we provide a blueprint to transfer chemical processes from batch to flow mode. The reaction of diphenyldiazomethane (DDM) with p-nitrobenzoic acid, conducted in batch and flow, was chosen for proof of concept.

连续流动化学: Diphenyldiazomethane 与p硝基苯甲酸的反应

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and ...

A Continuous-flow Photocatalytic Reactor for the Precisely Controlled Deposition of Metallic Nanoparticles

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic nanoparticles is developed. Guidelines for the replication of the reactor and its operation are provided in detail. Three different composite systems (Pt/graphene, Pt/TiO2, and Au/TiO2) with monodisperse and uniformly distributed particles are produced by this reactor, and the photodeposition mechanism, as well as the synthesis optimization strategy, are discussed. The synthesis methods and their technical aspects are described comprehensively. The role of the ultraviolet (UV) dose (in each excitation pulse) on the photodeposition process is investigated and the optimum values for each composite system are provided.

For a continuous and scalable synthesis of noble-metal-based nanocomposites, a novel photocatalytic reactor is developed and its structure, operation principles, and product quality optimization strategies are described.

一种用于金属纳米粒子精确控制沉积的连续流动光催化反应器

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic ...

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands for in vivo investigations. Within this protocol, a robust and reliable remote-controlled radiosynthesis of [11C]SNAP-7941, an antagonist to the melanin-concentrating hormone receptor 1, is described. The radiosynthesis starts with cyclotron produced [11C]CO2 that is subsequently further reacted via a gas-phase transition to [11C]CH3OTf. Then, this reactive intermediate is introduced to the precursor solution and forms the respective radiotracer. Chemical as well as the radiochemical purity are determined by means of RP-HPLC, routinely implemented in the radiopharmaceutical quality control process. Additionally, the molar activity is calculated as it is a necessity for the following real-time kinetic investigations. Furthermore, [11C]SNAP-7941 is applied to MDCKII-WT and MDCKII-hMDR1 cells for evaluating the impact of P-glycoprotein (P-gp) expression on cell accumulation. For this reason, the P-gp expressing cell line (MDCKII-hMDR1) is either used without or with blocking prior to experiments by means of the P-gp substrate (&#177;)-verapamil and the results are compared to the ones observed for the wildtype cells. The overall experimental approach demonstrates the importance of a precise time-management that is essential for every preclinical and clinical study using PET tracers radiolabelled with short-lived nuclides, such as carbon-11 (half-life: 20 min).

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Here, we represent a protocol for the fully automated radiolabelling of [11C]SNAP-7941 and the analysis of the real-time kinetics of this PET-tracer on P-gp expressing and non-expressing cells.

[11C_SNAP-7941] 自动合成和实时动力学评估的技术方面

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands ...

Optimization of Radiochemical Reactions using Droplet Arrays

Current automated radiosynthesizers are designed to produce large clinical batches of radiopharmaceuticals. They are not well suited for reaction optimization or novel radiopharmaceutical development since each data point involves significant reagent consumption, and contamination of the apparatus requires time for radioactive decay before the next use. To address these limitations, a platform for performing arrays of miniature droplet-based reactions in parallel, each confined within a surface-tension trap on a patterned polytetrafluoroethylene-coated silicon "chip", was developed. These chips enable rapid and convenient studies of reaction parameters including reagent concentrations, reaction solvent, reaction temperature and time. This platform permits the completion of hundreds of reactions in a few days with minimal reagent consumption, instead of taking months using a conventional radiosynthesizer.

This method describes the use of a novel high-throughput methodology, based on droplet chemical reactions, for the rapid and economical optimization of radiopharmaceuticals using nanomole amounts of reagents.