Bayesian estimation of Pseudomonas aeruginosa viscoelastic properties based on creep responses of wild type, rugose, and mucoid variant biofilms.

Pseudomonas aeruginosa biofilms are relevant for a variety of disease settings, including pulmonary infections in people with cystic fibrosis. Biofilms are initiated by individual bacteria that undergo a phenotypic switch and produce an extracellular polymeric slime (EPS). However, the viscoelastic characteristics of biofilms at different stages of formation and the contributions of different EPS constituents have not been fully explored. For this purpose, we develop and parameterize a mathematical model to study the rheological behavior of three biofilms - P. aeruginosa wild type PAO1, isogenic rugose small colony variant (RSCV), and mucoid variant biofilms against a range of experimental data. Using Bayesian inference to estimate these viscoelastic properties, we quantify the rheological characteristics of the biofilm EPS. We employ a Monte Carlo Markov Chain algorithm to estimate these properties of P. aeruginosa variant biofilms in comparison to those of wild type. This information helps us understand the rheological behavior of biofilms at different stages of their development. The mechanical properties of wild type biofilms change significantly over time and are more sensitive to small changes in their composition than the other two mutants.

Deformation of an Encapsulated Leukemia HL60 Cell through Sudden Contractions of a Microfluidic Channel.

Migration of an encapsulated leukemia HL60 cell through sudden contractions in a capillary tube is investigated. An HL60 cell is initially encapsulated in a viscoelastic shell fluid. As the cell-laden droplet moves through the sudden contraction, shear stresses are experienced around the cell. These stresses along with the interfacial force and geometrical effects cause mechanical deformation which may result in cell death. A parametric study is done to investigate the effects of shell fluid relaxation time, encapsulating droplet size and contraction geometries on cell mechanical deformation. It is found that a large encapsulating droplet with a high relaxation time will undergo low cell mechanical deformation. In addition, the deformation is enhanced for capillary tubes with narrow and long contraction. This study can be useful to characterize cell deformation in constricted microcapillaries and to improve cell viability in bio-microfluidics.

Improving viability of leukemia cells by tailoring shell fluid rheology in constricted microcapillary.

Encapsulated cell therapy has shown great potential in the treatment of several forms of cancer. Microencapsulation of these cancer cells can protect the core from the harmful effects of the neighboring cellular environment and can supply nutrients and oxygen. Such an encapsulation technique ensures cell viability and enables targeted drug delivery in cancer therapy. The cells immobilized with a biocompatible shell material can be isolated from the ambient and can move in constricted microcapillary. However, transportation of these cells through the narrow microcapillary may squeeze and mechanically damage the cells which threaten the cell viability. The cell type, conditions and the viscoelastic properties of the shell can dictate cell viability. A front-tracking numerical simulation shows that the engineered shell material with higher viscoelasticity improves the cell viability. It is also shown that low cortical tension of cells can contribute to lower cell viability.

Geometry Effects of Axisymmetric Flow-Focusing Microchannels for Single Cell Encapsulation.

Cell microencapsulation is a promising technique to protect living cells in biomedical applications. Microfluidic devices can be utilized to control the production of high-throughput cell-laden droplets. This paper demonstrates the effects of flow-focusing geometry on the droplet size, frequency of droplet generation, and number of cells per droplet. Orifice radius, orifice length, and nozzle-to-orifice distance can significantly influence the flow-field and manipulate droplet formation. This paper analyzes these geometry effects using a numerical front-tracking method for the three fluid phases. It is found that as the orifice radius increases, the drop size and the number of cells in the droplet increase. For a short orifice radius, increasing the orifice length results in the generation of smaller droplets at higher frequency and fewer cells per droplet. On the other hand, for a longer orifice, droplet production is invariant with respect to orifice length. It is also found that shorter distances between the nozzle and the orifice lead to a more controlled and uniform production of droplets. When the nozzle-to-orifice length is increased, the droplet formation becomes non-uniform and unpredictable. Probability charts are plotted with respect to the orifice length and orifice radius, which show that a greater than 50 % probability of single cell encapsulation can be achieved consistently.