Projects

Targeted drug delivery to the tumor is essential for effective cancer eradication while maintaining the use of a moderate drug dose to limit general toxicity. Drug delivery vectors with uniform geometric shapes have been shown to accumulate naturally in specific organs and tissue throughout the body. Here we explore a cost-effective, wafer-scale method of fabricating discoidally-shaped porous silicon nanoparticles (PSNDs) for camptothecin delivery to targeted cells.

It is an established fact that when the cellular membrane experiences shear force by passing through constrictions, transient nano-scale pores develop across the cellular membrane due to the the disruption in the organization of the lipid bilayer. This disruption is temporary since the phospholipids reassemble again to close the gaps. During this window of time, it is possible to introduce the desired cargo molecules to the cell interior from the extracellular environment through passive diffusion along the concentration gradient. Here we describe an entirely elastic 100 µm wide microfluidic PDMS channel that can be deformed on demand to create constrictions with finely tuned dimensions. These constrictions were then used to disrupt the membranes of cells passing through the channel to deliver a myriad of bioactive agents.

At the height of the COVID-19 pandemic, there was a severe shortage in testing kits available, which greatly impeded global efforts to contain the spread of the virus. This partly stemmed from the time neededt o isolate the virus, and identify the unique targetable capsid proteins that characterize it. Once identified, targeting antibodies can be developed to identify the virus. This introduces another delay where production facilities need to synthesize the needed antibodies for the testing kits. The use of the virus mass as a fingerprint instead provides an alternative method of identifying the presence of the infection since each virus is comprised of different ratios of capsid, proteins, and RNA. These all contribute differently to the total mass of the individual virion. Nanoelectromechanical resonators are ideal for measuring the mass of single nanoparticles in the size range of viruses. However, these systems are notoriously low-throughput due to the difficulty of delivering the analyte nanoparticles to the micro-scale resonating element. Here, using a combination of electrospray ionization (ESI) and an integrated electrostatic focusing lens, we were able to increase the throughput of virus analyte sensing by 100-fold, cutting down each individual analysis from several hours down to 5-10 minutes. 

In order to allow bioactive molecules (proteins, mRNA, fluorescent markers, etc.) to enter the cellular cytosol, it is essential to find means to transport the bioactive agent across the cellular membrane without major disruption to normal physiological functions. Here, we explore wafer-scale nan-sized vertically-aligned silicon nanowires which act like nanoinjectors that can delivery the desired bioactive cargo directly to the interior of cells cultured on top of the nanostructured surface. This opens the way for mass production of cancer-fighting CAR-T cells or for the programmed differentiation of stem cells.

Laser Desorption/Ionization (LDI) Mass Spectrometry is a powerful low-fragmentation mass spectrometry technique that allows for the mass analysis of small intact molecules (such as drugs of abuse). In the context of competitive sports, the technique is used to screen for performance-enhancing drugs. The sample is collected from bodily fluids (saliva, urine, etc.) and mixed with a UV-absorbing matrix which is then struck by a laser beam in vacuum to ionize and release the intact molecules into a time-of-flight detector to measure their mass. However this is a slow and tedious process that requires time and expertise. Here, we developed a nanoengineered silicon substrate where the physiological fluids can be spotted directly without sample preparation. The nanostructures on the substrate facilitate the absorption and transfer of the UV energy to the analyte molecules without causing significant fragmentation. This allows for a rapid screening process with minimal sample volume.

Impedance cytometry is a well established method whereby microparticles can be sized and counted in a rapid flow-through manner. The operational principle is that a low-frequency (RF) electric field is applied between two electrodes surrounding a microfluidic constriction. The ions in solution facilitate the flow of current between the two electrodes. When particles pass by the constriction, they block part of the current from flowing, and the magnitude of impedance increase correlates directly with particle volume. In fact, most 3-part haematology analyzers that provide RBC counts and sizes operate using this principle. However, at low frequencies, the surface of the particle acts as a dielectric, preventing the electric field from penetrating the interior of the particle. It is therefore impossible to distinguish between particles of different materials passing through the sensor (i.e. for impedance, a biological cell is equivalent to a plastic, glass or metal particle of the same size). Here, we developed a high-frequency (microwave) sensor that works in tandem with a low-frequency counterpart to gain information about not only the size, but also the material of the passing particle. At high frequency, the electric field penetrates the particle/cell interior. By normalizing the change in resonance frequency shift to the particle size, we obtain the particle's electric permittivity which is a fundamental property related to the material composition of the particle. With this sensor, in addition to gathering size and count information, we can now distinguish between cells, plastics, ceramics, and metal since each material will exhibit a different electrical permittivity value.