Raman spectra-based deep learning: A tool to identify microbial contamination.

Deep learning has the potential to enhance the output of in-line, on-line, and at-line instrumentation used for process analytical technology in the pharmaceutical industry. Here, we used Raman spectroscopy-based deep learning strategies to develop a tool for detecting microbial contamination. We built a Raman dataset for microorganisms that are common contaminants in the pharmaceutical industry for Chinese Hamster Ovary (CHO) cells, which are often used in the production of biologics. Using a convolution neural network (CNN), we classified the different samples comprising individual microbes and microbes mixed with CHO cells with an accuracy of 95%-100%. The set of 12 microbes spans across Gram-positive and Gram-negative bacteria as well as fungi. We also created an attention map for different microbes and CHO cells to highlight which segments of the Raman spectra contribute the most to help discriminate between different species. This dataset and algorithm provide a route for implementing Raman spectroscopy for detecting microbial contamination in the pharmaceutical industry.

Inertial migration of a deformable capsule in an oscillatory flow in a microchannel.

Dynamics of a deformable capsule in an oscillatory flow of a Newtonian fluid in a microchannel has been studied numerically. The effects of oscillation frequency, capsule deformability, and channel flow rate have been explored by simulating the capsule within a microchannel. In addition, the simulation captures the effect of the type of imposed pressure oscillations on the migration pattern of the capsule. An oscillatory channel flow enables the focusing of extremely small biological particles by eliminating the need to design impractically long channels. The presented results show that the equilibrium position of the capsule changes not only by the addition of an oscillatory component to the pressure gradient but it also is influenced by the capsule deformability and channel flow rate. Furthermore, it has been shown that the amplitude of oscillation of capsules decreases as the channel flow rate and the rigidity of the capsule increases.

Towards smart self-clearing glaucoma drainage device.

For patients who are unresponsive to pharmacological treatments of glaucoma, an implantable glaucoma drainage devices (GDD) are often used to manage the intraocular pressure. However, the microscale channel that removes excess aqueous humor from the anterior chamber often gets obstructed due to biofouling, which necessitates additional surgical intervention. Here we demonstrate the proof-of-concept for smart self-clearing GDD by integrating magnetic microactuators inside the drainage tube of GDD. The magnetic microactuators can be controlled using externally applied magnetic fields to mechanically clear biofouling-based obstruction, thereby eliminating the need for surgical intervention. In this work, our prototype magnetic microactuators were fabricated using low-cost maskless photolithography to expedite design iteration. The fabricated devices were evaluated for their static and dynamic mechanical responses. Using transient numerical analysis, the fluid-structure interaction of our microactuator inside a microtube was characterized to better understand the amount of shear force generated by the device motion. Finally, the anti-biofouling performance of our device was evaluated using fluorescein isothiocyanate labeled bovine serum albumin. The microactuators were effective in removing proteinaceous film deposited on device surface as well as on the inner surface of the microchannel, which supports our hypothesis that a smart self-clearing GDD may be possible by integrating microfabricated magnetic actuators in chronically implanted microtubes.

Elasto-inertial migration of deformable capsules in a microchannel.

In this paper, we study the dynamics of deformable cells in a channel flow of Newtonian and polymeric fluids and unravel the effects of deformability, elasticity, inertia, and size on the cell motion. We investigate the role of polymeric fluids on the cell migration behavior and the performance of inertial microfluidic devices. Our results show that the equilibrium position of the cell is on the channel diagonal, in contrast to that of rigid particles, which is on the center of the channel faces for the same range of Reynolds number. A constant-viscosity polymeric fluid, modeled using an Oldroyd-B constitutive equation, drives the cells toward the channel centerline, while a shear-thinning polymeric fluid, modeled using a Giesekus constitutive equation, pushes the cells toward the channel wall. The findings of this paper suggest that the addition of polymers in microfluidic devices can be used to enhance the throughput of cell focusing and separation devices at a low cost. This study provides an insight on the role of rheological properties of the fluid and the ways that they can be tuned to control the focal position of the cells.

Deformation and buckling of microcapsules in a viscoelastic matrix.

In this paper, we numerically study the dynamics of (1) a Newtonian liquid-filled capsule in a viscoelastic matrix and that of (2) a viscoelastic capsule in a Newtonian matrix in a linear shear flow using a front-tracking method. The numerical results for case (1) indicate that the polymeric fluid reduces the capsule deformation and aligns the deformed capsule with the flow direction. It also narrows the range of tension experienced by the deformed capsule for case (1), while the tank-treading period significantly increases. Interestingly, the polymeric fluid has an opposite effect on the tank-treading period and the orientation angle of case (2), but its effect on the deformation is similar to case (1).