Multi-functional Nanocomposites for Biological Labeling and Diagnostics - There have been tremendous advances in the development of in-situ labeling and screening of different biological entities, ranging from cells to DNAs. Many approaches have been developed for this purpose, such as chemical encoding with molecular tags, organic fluorophores, fluorescent colloids, and Raman fingerprints. The development of labeling materials has been critically important. Some materials such as quantum nanodots, organic dyes and metal nanoparticles have been extensively used for biological labeling, however, they have to be surface modified to better suit their integration with biological systems.

Recently, synthesis of monodisperse polymer nanospheres has stimulated great interest and incorporation of fluorophores in these nanospheres is particularly attractive. In these nanocomposites, organic polymer can not only stabilize the nanoparticles in a solid matrix, but also effectively combine the peculiar features of organic and inorganic components and thus resulting in novel properties. These materials can bring new and unique capabilities to a variety of biomedical applications ranging from diagnosis of diseases to novel therapies.

Fluorescence based biodetection & bioimaging
Imaging-guided cancer therapy


Mechanobiology:

The foundation of mechanobiology lies in the application of biomechanics and biophysics in elucidating the physiology as well as pathophysiology of proteins, cells, tissues and organs. This can range from the intracellular interactions of proteins that control gene transcription or the protein complexes that drive cell migration to the physical interactions between cells and their external microenvironment which can influence processes such as stem cell differentiation, epithelium formation and wound healing. As such, any drastic changes in physical factors such as molecular and cellular mechanical properties or the microenvironment can potentially result in pathological processes (a.k.a. mechanopathology). Here, we investigate human diseases related to cancer, malaria, sepsis and aging using micro- and nanomechanical tools such as laser tweezers, atomic force microscopy, microfluidics, cell migration and cell adhesion assays. We hope these studies will not only provide better insights into our health and disease, but will also lead to the establishment of novel biophysical markers for disease detection, diagnosis, therapy and personalized medicine.


Microfluidics:

Dealing with rare single cells and being able to manipulate and retrieve them are essential first steps for disease detection and diagnosis. We are currently developing non-antibody mechanobiology based microfluidic devices to detect, diagnose and treat human diseases such as cancer, malaria and sepsis. The principle is simple and makes use of the fact that diseased cells have biomechanical properties such as cell stiffness and size that are significantly different from that of their healthy counterparts or from a population of other cell types. These devices are microfluidics based and possess several advantages: reduced sample volumes, faster processing time, high sensitivity and spatial resolution, low cost and portability. Using this approach, we hoped to develop microfluidic devices for healthcare applications in diagnosis, prognosis, therapy and personalized medicine.


Tunable Nanomaterials:

Touted as the rising stars in materials science and engineering, 2D materials and nanofibers have been subjected to intense investigations due to their unique and superior properties such as high surface to volume ratio, excellent physicochemical properties as well as the ability to tailor or tune these nanomaterials for numerous applications. Here, we investigate how we can tune these nanomaterials for biological and biomedical applications. These include the use of graphene as a stem cell culture platform to enhance and accelerate proliferation and differentiation of stem cells, graphene oxide for antibacterial and antithrombotic coating application, 2D materials as sensing elements for disease detection and health monitoring, and polymer nanofibers for tissue engineering applications.


Translation:

Technologies developed on the bench can only make an impact when they move from the lab to the industry and market. In creating our mechanobiologically inspired technologies, we are always mindful of how they can ultimately benefit the patients and the society. In our lab, we have and will continue to translate some of our most promising technologies into products through new startups, licensing or corporate partnership to eventually bring them from the bench to bedside.


Startups:

Some of our startups that we have co-founded to commercialize technologies developed in our lab include Clearbridge Biomedics, Clearbridge Nanomedics and Clearbridge mFluidics.


Biomicrodevices: In an interdisciplinary approach we combine microfabrication, surface chemistry and molecular biology to create novel devices using biomolecules (DNA or proteins) for analytical purpose. The final aim is the full integration of biological materials into microdevice fabrication processes, targeting mass production compatibility.

Encapsulation: By using the Layer-by-Layer (LbL) Technology we are creating core shell materials and smart capsules. The LbL technology allows nanoengineering of surface properties to tailor and incorporate different properties into capsules and nano/microparticles.  




 

The application of nanomaterials in biology has shown promise in addressing challenges in modern medicine. However, nanoparticles tend to be sticky due to their nanoscale nature, resulting in undesirable biological responses such as aggregation and non-specific biomolecular adsorption, which forms the root of many downstream issues in nanomedicine: loss of physical properties, unwanted immune responses, poor targeting efficacy and undesirable clearance etc.

 

Nanomedicine

Instead of viewing nanomaterials as abiological entities with undesirable surface issues, we like to view them as “pseudo” cellular entities with an innate behavior to self assemble or adsorb biomolecules, and an acquired behavior with smart surface engineering.

 

Nanoparticles

 

We are interested to embrace these behaviors so as to harness their physical properties effectively for probing and modulating biological processes both at the cellular and tissue level.







Single Cell Analysis::

Understanding the molecular mechanisms of these different cells is the key to understanding the basis of human health and conditions that leads to disease. To date, however, biological measurements are largely applied to bulk cells, which mask important cell-to-cell variations in tissues that give rise to diverse phenotypes. We aim to enable high resolution measurements of these molecular profiles at the single cell level, to identify the continuum of cellular states in a population that lead to function or disease. Ultimately, by integrating these multidimensional measurements, we hope to model the single cell as a system of interacting networks at multiple scales. These cellular models, as the basis of “Single Cell Systems Biology”, will be instrumental in our understanding and prediction of how a cell changes over time and under varying condition. This will create potential for entirely new kinds of explorations, including drug designs to improve cellular function and eliminate diseases.

Left: Technology platforms for single cell analysis


Microfluidics:

Microfluidics presents many opportunities to improve biological research and healthcare. On one hand, micro and nanoscale confinement can lead to novel physical phenomena that can be exploited. Making use of the electrokinetic phenomena at the micro-nano interface, we develop signal enhancement platforms that can lead to ultrasensitive biological assays for diagnostics applications. We also design novel devices to perform continuous flow separation or concentration of cells or biomolecules based on their physical properties.

On the other hand, automated microfluidics platform can be used to perform high-throughput biochemical assays using much less samples and reagents. We developed microfluidics valve-based large scale integrated platform to allow simultaneous screening of thousands of protein-ligand interactions via fluorescence polarization in a single chip. We are also developing new automated microfluidic platforms to enable more sensitive and accurate measurements in single cells.

Left: Microfluidic large scale integrated platform for high throughput screening