Dr.Liu Lab: Bio Nanomechanics, LU

 

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Current Projects  


                     

Project 1: An Integrated Biometric Platform for Evaluation of Nanomedicine Delivery
The goal of this project is to develop a vascular model that effectively mimic in vivo conditions. Endothelial cells (ECs) are grown on flow channels made of polydimethylsiloxane. The flow channels consist of a top and bottom layer, separated by a semi-permeable membrane having separate inlet and outlet. This allows to locally induce inflammatory responses on the ECs growing in the top channel. This is achieved by designing the bottom channel such that only specific sections of the top endothelial cell layered layer is exposed to cytokines (Fig 1).

Blood vessels consist of a smooth muscle cell layer over the endothelial cell layer. Its functions are a result of interaction between these cell layers. Intelligent engineering of the top and bottom channels of our device can mimic this interaction (Fig 2). This takes our goal of mimicking the blood vessels closer to in vivo conditions to the next level. Drug carrier mimicking particle distribution studies will be conducted in this vascular model.
   
   Fig. 1                       Fig. 2
   
   Fig. 3                      Fig. 4
Fig. 3: Blood vessel mimicking device with different dyes in top straight channel and bottom S channel separated by a semi permeable membrane. Fig. 4: Calcein AM stained BAOEC on membrane top channel




Project 2: Efficient Rare Cell Capturing in Microfluidic Devices via Multiscale Surface Design

The goal of this project is to design a novel surface that could significantly enhance rare cell capture efficacy and selectivity. Specifically, we will design and fabricate a hierarchical surface consisting of patterned structures at two difference length scales: a micro-scale surface of ripples or herringbone structure and an array of nanoparticles or nanopillars. The micro-scale sinusoidal ripples and herringbone structures will generate micro-vortices to enhance cell-wall collision, provide larger adhesion area, avoid non-specific cell adhesion and possible cell damage, and enable accurate cell counting; the nanostructures will complement microvilli on cell membranes, thus, improve both interaction specificity and cell capturing efficiency.
   
   Fig. 1                      Fig. 2
   
   Fig. 3                      Fig. 4
Fig. 1: Schematic description about the interaction between CTCs and wave-herringbone substrate. Spheres stand for CTCs; Fig. 2: Computational modeling about the dynamics of CTCs; Fig. 3: CTCs captured on the wave-herringbone substrate. Dots circled represent captured CTCs; Fig. 4: Cell-Nanopillar interaction under shear flow.




Project 3: Multiscale Modeling on Predicting Nanoparticle Delivery and Cell Dynamics

The goal of this project is to study NP transport, binding and distribution in vascular environment through multiscale Modeling. The blood and cells are modeled through FEM method, while NPs are tracked though Brownian motion. For details, see Jifu's personal webpage.

Currently we are developing a new mesoscale simulation tool based on Lattice Boltzmann fluid solver and particle based cell model to address more challenging problems raised in biomedical research.
   




Project 4: 3D Printing / Additive Manufacturing

Our goal is to design an innovative, cost effective, and energy-efficient 3D additive manufacturing device which can achieve rapid fabrication, high resolution, complex shapes, and selectable building volume. Currently, we have developed SLA and DLP based 3D printer which utilizes the UV light source to cure the liquid photocurable resin. We have built devices with different printing resolution and building volume. Our X-Y printing resolution ranges from 15m to 100m, Z resolution ranges from 25 m to 500m. A 20mm tall prototype needs only 0.5 hours to print with a 100m Z resolution.

We develop the manufacturing material with a variety of material properties and color as well. Our goal is to create photosensitive resins that have diverse properties and apply them to diverse fields. Diverse properties:
Super hard, rubber-like, colorful, colorless transparent, high resolution, biocompatible.

Diverse applications:
Tools and other daily applications, Artifacts, Biomedical devices, Tissue scaffolds...
   
   Fig. 1 Left: A 75mm tall "Eiffel Tower" with 30 m X-Y resolution; Right: 3D printing materials with different properties and colors.
   
   Fig. 2 3D additive manufacturing devices with various printing resolution and quality.
   
   Fig. 3 3D printing samples (Tools, decorations, and a full set of teeth).
   






Past Projects

  

Project 5: Characterization of Nanosensor Field-Assisted Detection of Biomarkers at Ultralow Concentration

The goal of this project is to improve the detection efficiency of biomarkers at ultralow concentration with the assistance of electric field. Coarse-grained models of biomolecule-biosensor surface interaction have been established for studying the biomarkers detection process under different conditions. The coarse-grained model can work on simulations with longer time scale and larger size scale which are inaccessible for full-atomistic MD simulation. Results showed the application of electric field, proper coating molecules and denser coating molecules will all well-orientate antibodies, reduce the biomarkers detection time and enhance the efficiency of biosensors consequently.
   
   Fig. Schematics of antibody orientation and binding.

Project 6: Mechanical properties of nano-structure constructed by DNA-grafted nanoparticles assembly

The goal of this project is to test mechanical properties of novel nanostructures assembled by DNA-AuNP conjugates. Coarse-grained models of DNA-AuNP conjugates are created for constructing one-dimensional (nanoworm), two dimensional (nanosheet) and three dimensional (nanocrystal) structures. The mechanical properties of these structures are tested by coarse-grained molecular dynamics simulations. Potential applications of these novel structures include fields of drug delivery, image probing, thermal therapy, biodetection, chemical analysis, etc.
   
   Fig. 1 Dimer                 Fig. 2 DNA magnetic microparticle chain
                   

Project 7: Cell adhesion and alignment of cells on a curved surface

The goal of this project is to study the adhesion and alignment of endothelial cells in microfluidic channels. A micro wave pattern has been fabricated to investigate the cell adhesion. By comparing the cell adhesion on wave and flat surface, we want to investigate whether our wave pattern can help cell alignment and spreading.
   
Fig. Microscope image of endothelial cells. (A) Flat PDMS substrate after 24h; (B) 20m spacing, 6.6m height micro-wave after 24h;

Project 8: Confocal image of ssDNA-Au NP binding on red blood cell

   
   
Project 9: Predict NP Targeted Delivery Efficacy in Vascular Environment through Multi-scale Modeling
The goal of this project is to Predict NP Targeted Delivery Efficacy in Vascular Environment through Multi-scale Modeling. Specifically, we will reconstruct real human lung vascular 3-D model, based on MRI or CT image. Then through CFD method, simulate and compare the phenomena of NP delivery in both man-made simple branch and real lung model, in different conditions, include NP size, vascular inlet velocity and vascular geometry. Thus to characterize the rules to enhance the NP targeted delivery efficacy.
   
   
Project 10: Stent Testing Platform for Evaluation of Cell Damage and Regrowth
The goal of this project is the development of a testing platform which closely mimics the events and conditions seen during stent implantation via balloon dilation catheter. Specifically the platform is focused on the effects which varying stet materials have on cultured monolayers of cells. This is achieved through culturing endothelial cells (ECs) into dishes and then applying a downward force with a small section of stent material with the use of a micromanipulator (Fig 1).

Cellular damage, death and regrowth are monitored through a variety of cellular stains and assays combined with bright-field and fluorescence microscopy. Future versions of the platform will have ECs cultured in 3D tubular geometries, and will make use of a balloon dilation catheter for the application of stent pressure into the cultured monolayer of cells.
   
   Fig. 1 A schematic of micromanipulator.
   
   Fig. 2: Bright-field image of EC cultured monolayer after depression of stent material via micromanipulator.
   Fig. 3: Bright-field image of EC cultured monolayer after depression and shearing of stent material via micromanipulator.
 

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