A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

Manneschi, Chiara; Pereira, Rui C.; Marinaro, Giovanni; Bosca, Alessandro; Francardi, Marco; Decuzzi, Paolo

doi:10.1007/s10404-016-1775-5

Cited by 16 publications

(18 citation statements)

References 33 publications

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“…The single channel microfluidic chip was fabricated following protocols previously demonstrated by the authors. (Manneschi et al 2016) Briefly, a SU8-50 master was used as a mold for PDMS replicas of the chip. First a 40 µm thick layer of SU8-50 photoresist (MicroChem) was spin coated on a silicon wafer (4"-P doped -<100> -10 ÷ 20 W/cm 2 -525 µm thick, from Si-Mat) at 2000 rpm for 30 s. Then, the negative SU8-50 template was pre-and soft baked for solvent evaporation; exposed to UV light and baked again for epoxy crosslinking; and finally developed.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the relative contribution of vascular inflammation and blood rheology in metastatic spreading

et al. 2018

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Vascular adhesion of circulating tumor cells (CTCs) is a key step in cancer spreading. If inflammation is recognized to favor the formation of vascular "metastatic niches," little is known about the contribution of blood rheology to CTC deposition. Herein, a microfluidic chip, covered by a confluent monolayer of endothelial cells, is used for analyzing the adhesion and rolling of colorectal (HCT-15) and breast (MDA-MB-231) cancer cells under different biophysical conditions. These include the analysis of cell transport in a physiological solution and whole blood over a healthy and a TNF-α inflamed endothelium with a flow rate of 50 and 100 nl/min. Upon stimulation of the endothelial monolayer with TNF-α (25 ng/ml), CTC adhesion increases from 2 to 4 times whilst cell rolling velocity only slightly reduces. Notably, whole blood also enhances cancer cell deposition from 2 to 3 times, but only on the unstimulated vasculature. For all tested conditions, no statistically significant difference is observed between the two cancer cell types. Finally, a computational model for CTC transport demonstrates that a rigid cell approximation reasonably predicts rolling velocities while cell deformability is needed to model adhesion. These results would suggest that, within microvascular networks, blood rheology and inflammation contribute similarly to CTC deposition, thereby facilitating the formation of metastatic niches along the entire network, including the healthy endothelium. In microfluidic-based assays, neglecting blood rheology would significantly underestimate the metastatic potential of cancer cells.

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Section: Methodsmentioning

confidence: 99%

Deciphering the relative contribution of vascular inflammation and blood rheology in metastatic spreading

et al. 2018

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“…1a) (Manneschi et al 2016). First, a negative mold of the channel is generated, upon UV light cross-linking, baking and development of a SU-8 film.…”

Section: Cell Rolling In a Capillary Flowmentioning

confidence: 99%

Predicting different adhesive regimens of circulating particles at blood capillary walls

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et al. 2017

Microfluid Nanofluid

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“…The chips were fabricated by using a replica molding approach as previously described. 31 Blood was collected in heparin containing tubes. To create the clot, two tubes, connected to the syringe pump, were inserted in the two inlets on the microfluidic chip.…”

Section: Synthesis Of Discoidal Polymeric Nanoconstructs (Dpns) Coatementioning

confidence: 99%

Erythrocyte-Inspired Discoidal Polymeric Nanoconstructs Carrying Tissue Plasminogen Activator for the Enhanced Lysis of Blood Clots

et al. 2018

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Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano therapeutic agent is realized by directly associating the clinical formulation of tPA to the porous structure of soft discoidal polymeric nanoconstructs (tPA-DPNs). The porous matrix of DPNs protects tPA from rapid degradation, allowing tPA-DPNs to preserve over 70 % of the tPA original activity after 3 h of exposure to serum proteins. Under dynamic conditions, tPA-DPNs dissolve clots more efficiently than free tPA, as demonstrated in a microfluidic chip where clots are formed mimicking in vivo conditions. At 60 min post treatment initiation, the clot area reduces by half (57 + 8 %) with tPA-DPNs, whereas a similar result (56 + 21 %) is obtained only after 90 min for free tPA. In murine mesentery venules, the intravenous administration of 2.5 mg/kg of tPA-DPNs resolves almost 90 % of the blood clots, whereas a similar dose of free tPA successfully recanalize only about 40 % of the treated vessels. At about 1/10 of the clinical dose (1.0 mg/kg), tPA-DPNs still effectively dissolve 70 % of the clots, whereas free tPA works efficiently only on 16 % of the vessels. In vivo, discoidal tPA-DPNs outperform the lytic activity of 200 nm spherical tPA-coated nanoconstructs in terms of both percentage of successful recanalization events and clot area reduction. The conjugation of tPA with preserved lytic activity, the deformability and blood circulating time of DPNs together with the faster blood clot dissolution would make tPA-DPNs a promising nanotool for enhancing both potency and safety of thrombolytic therapies.

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A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

Cited by 16 publications

References 33 publications

Deciphering the relative contribution of vascular inflammation and blood rheology in metastatic spreading

Deciphering the relative contribution of vascular inflammation and blood rheology in metastatic spreading

Predicting different adhesive regimens of circulating particles at blood capillary walls

Erythrocyte-Inspired Discoidal Polymeric Nanoconstructs Carrying Tissue Plasminogen Activator for the Enhanced Lysis of Blood Clots

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