Our primary research interest is Micro/Nano Engineering for Biology and Medicine. We are using combined experimental and computational approaches to characterize the interfacial phenomena at the micro/nano scale and in biological systems. We collabortate with partners in industry and hospital in commertialization and application of our techniques. In recent years, the Liu's group have been exploring three main areas: Nanomedicine, Biomimetic Lab on Chip Devices, and Additive manufacturing.
-3D Printning and Additive Manufacturing
-Targeted Drug Delivery
-Multiscale Modeling of Bio-Nano Systems
Magnetic particles assisted capture and release of rare tumor cells using wavy-herringbone structured microfluidic devices
The goal of this project is to not only enumerate the circulating tumor cells from patient blood, but also isolate them for post analyses, such as cell culture, single cell sequencing and mutation study. Specifically, a wavy-herringbone (wavy-HB) structured microfluidic device was used to effectively and selectively capture and release circulating tumor cells (CTCs) by using immunoaffinity and magnetic force. The device was designed to create passive turbulence and increase the possibility of tumor cells colliding onto the device wall. Under an external magnetic field, magnetic particles (MPs) coated with anti-EpCAM against tumor cell surface protein (EpCAM) were immobilized over the wavy-HB surface to capture tumor cells. After removing the magnetic field, the captured cells with surplus MPs were released from the device and collected, thus cells could be re-cultured for further analysis. Such method can potentially be used for CTCs sorting from patient blood samples, CTCs concentration monitoring, therapeutic guidance and drug dosage choice, and further study of tumors, such as drug screening and tumor mutations.
Multiscale Predictive Modeling of Blood Cell Damage with Experimental Verification
This project aims to develop a multiscale model to characterize blood cell damage under complex flow conditions. Blood damage is an important concern for various blood wetting medical devices. The goal of this proposal is to study blood cell damage at molecular and cellular level using combined computational modeling and experimental approaches. Specifically, we will develop a multiscale model that links molecular scale pores formation to cell membrane damage and hemoglobin release. The multiscale computational modeling will be applied for the first time to study of cellular flow over various channel geometries and clinically relevant devices with consideration of both hydrodynamics and membrane damage dynamics.
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 15µm to 100µm, Z resolution ranges from 25 µm to 500µm. A 20mm tall prototype needs only 0.5 hours to print with a 100µm 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...
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
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. 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.
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.
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.
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.
Mechanical properties of nano-structure constructed by DNA-grafted nanoparticles assembl
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.
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.
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.
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. 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.
Oak Ridge Associated University