?SynRAM 3D炎癥模型芯片流體剪切分析芯片SynVivo的SynRAM™3D炎癥模型芯片系統(tǒng)

可以在現(xiàn)實(shí)和動態(tài)的環(huán)境中研究整個炎癥途徑。通過用內(nèi)皮細(xì)胞管腔重建共培養(yǎng)的組織和/或腫瘤細(xì)胞的組織切片，SynVivo平臺可在平臺上提供包括流動和剪切在內(nèi)的生理逼真的模型，并能夠?qū)崟r跟蹤滾動，粘附和遷移過程。該模型已經(jīng)成功地針對體內(nèi)研究進(jìn)行了驗證，該研究顯示出與滾動速度，粘附模式和遷移過程具有*的相關(guān)性（Lamberti等，2014； Soroush等，2016）。

逼真模擬人體內(nèi)的血管血流ding尖的微流控技術(shù)，用于細(xì)胞培養(yǎng)和觀察細(xì)胞滾動、粘附、遷移的得力助手，可用于觀察細(xì)胞與細(xì)胞、細(xì)胞與配體之間的在流體狀態(tài)下互相作用的新型體外流體動力學(xué)平臺?

SynRAM能夠在一個實(shí)驗中實(shí)時評估細(xì)胞相互作用，包括多個細(xì)胞層的滾動，粘附和遷移，并代表與體內(nèi)結(jié)果密切相關(guān)的數(shù)據(jù)?

SynRAM 3D炎癥模型提供了一個現(xiàn)實(shí)的測試環(huán)境，其中包括：

微血管環(huán)境中的生理切應(yīng)力
具有*封閉腔的體內(nèi)類血管形態(tài)
細(xì)胞間相互作用的共培養(yǎng)能力
單個實(shí)驗的實(shí)時定量滾動，粘附和遷移數(shù)據(jù)

SynRAM能夠在一個實(shí)驗中實(shí)時評估細(xì)胞相互作用，包括通過多個細(xì)胞層的滾動，粘附和遷移，并代表與體內(nèi)結(jié)果密切相關(guān)的數(shù)據(jù)。

SynRAM的創(chuàng)新設(shè)計克服了流動室或基于Transwell室的測定法固有的當(dāng)前局限性。當(dāng)前的流動室設(shè)計過于簡單，缺乏微環(huán)境的規(guī)模和幾何形狀，無法模擬遷移。同樣，Transwell腔室無法解決體內(nèi)觀察到的流體剪切力和尺寸/拓?fù)浣Y(jié)構(gòu)，遷移的終點(diǎn)測量結(jié)果不可重現(xiàn)，并且無法提供實(shí)時可視化效果。

SynVivo的專有芯片設(shè)計范圍從復(fù)雜的體內(nèi)衍生微血管網(wǎng)絡(luò)（從數(shù)字化圖像獲得）到產(chǎn)生逼真的細(xì)胞組成和血管形態(tài)，從而導(dǎo)致剪切和流動條件變化，再到簡化的理想化網(wǎng)絡(luò)，旨在再現(xiàn)細(xì)胞組成以及恒定的剪切和流動條件。
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SynRAM 3D模型套件組件
可以以試劑盒形式購買使用SynRAM模型進(jìn)行測定所需的所有基本組件。 根據(jù)個人研究需求，您可以從SynRAM芯片的“理想化”或“微血管”配置中進(jìn)行選擇。 包括所有附件，包括管子，夾子，針頭和注射器。 入門工具包還將包括氣動啟動裝置（使用SynRAM進(jìn)行分析需要）。 套件內(nèi)容和說明

Kits include the following components:

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SynRAM successfully validated against in vivo data

SynRAM microfluidic chips comprising of realistic microvascular networks were used to understand the role of classical inhibitors of individual steps of the leukocyte adhesion cascade. Experimental results matched very well with in vivo data highlighting the unique ability of the platform for real-time analysis of these dynamic events in a morphologically realistic environment (Lamberti et al 2014).

Neutrophil rolling using SynRAM microfluidic chips is similar to leukocyte rolling in vivo; Box and whisker plots summarizes the comparison of leukocytes rolling velocity measured in vivo and in SynRAM chips and shows no significant difference (p=0.758; Mann-Whitney Rank Sum Test). The “+” marked in the box indicates the mean.

Neutrophil adhesion in SynRAM microfluidic chips is similar to leukocyte adhesion in vivo; Distribution of the number of adhered leukocytes and neutrophils as a function of distance from the nearest bifurcation in vivo in mouse cremaster muscle model and in vitro in microfluidic chips, respectively. Both histograms are skewed to the left indicating that leukocytes and neutrophils preferentially adhere near bifurcations with the peak occurring at one vessel or channel diameter from the nearest bifurcation.

Bioinspired Microfluidic Assay for In Vitro Modeling of Leukocyte–Endothelium Interactions. G. Lamberti, B. Prabhakarpandian, C. Garson, A. Smith, K. Pant, B. Wang, and M.F. Kiani. Anal. Chem., 2014, 86 (16), pp 8344–8351 DOI:10.1021/ac5018716

Investigation of the Effect of Blocking of Specific Steps of the Inflammation Pathway using Monoclonal Antibodies

Antibody blocking of specific steps in the adhesion/migration cascade downregulates other steps of the cascade; Monoclonal antibodies against E-selectin (aE-selectin), ICAM-1(aICAM-1), and PI3K (wortmannin) significantly reduced the number of rolling, adhering, and migrating neutrophils in SynRAM microfluidic devices.

Percent activity after treating cells with the respective antibody blockers in comparison to their corresponding control values.

Elucidation of the Mechanism of Protein Kinase C delta (PKCδ) in Sepsis Related Inflammation Response

The SynRAM model was used to identify the underlying mechanism of Protein Kinase C delta (PKCδ) dependent neutrophil-endothelium interactions which has been found to play a significant role in the inflammatory response.  Under physiological fluid flow conditions and using the simultaneous real-time monitoring ability of the entire inflammation process comprising of rolling, adhesion and migration, they found PKC?? was a critical regulator of human neutrophil adhesion and migration through human endothelial cells during inflammation.

PKCδ-TAT inhibitor significantly reduces migration of neutrophils from the vascular channels, across the inflammed endothelium (treated with TNF-α for 4 or 24 hour), into the tissue compartment in response to fMLP mediated signaling compared to untreated controls.

Immunohistochemical detection of myeloperoxidase (MPO) in representative lung tissue sections from 24 h post surgery.  Few MPO-positive cells in Sham surgery. Sepsis induces the infiltration of numerous MPO-positive cells throughout the lung parenchyma. PKCδ-TAT Inhibitor significantly reduces sepsis-induced, MPO-positive cell numbers in the lung indicating decreased neutrophil migration.

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