Electric field-mediated adhesive dynamics of cells inside bio-functionalised microchannels offers important cues for active control of cell-substrate adhesion.

Adhesive dynamics of cells plays a critical role in determining different biophysical processes orchestrating health and disease in living systems. While the rolling of cells on functionalised substrates having similarity with biophysical pathways appears to be extensively discussed in the literature, the effect of an external stimulus in the form of an electric field on the same remains underemphasized. Here, we bring out the interplay of fluid shear and electric field on the rolling dynamics of adhesive cells in biofunctionalised micro-confinements. Our experimental results portray that an electric field, even restricted to low strengths within the physiologically relevant regimes, can significantly influence the cell adhesion dynamics. We quantify the electric field-mediated adhesive dynamics of the cells in terms of two key parameters, namely, the voltage-altered rolling velocity and the frequency of adhesion. The effect of the directionality of the electric field with respect to the flow direction is also analysed by studying cellular migration with electrical effects acting both along and against the flow. Our experiment, on one hand, demonstrates the importance of collagen functionalisation in the adhesive dynamics of cells through micro channels, while on the other hand, it reveals how the presence of an axial electric field can lead to significant alteration in the kinetic rate of bond breakage, thereby modifying the degree of cell-substrate adhesion and quantifying in terms of the adhesion frequency of the cells. Proceeding further forward, we offer a simple theoretical explanation towards deriving the kinetics of cellular bonding in the presence of an electric field, which corroborates favourably with our experimental outcome. These findings are likely to offer fundamental insights into the possibilities of local control of cellular adhesion via electric field mediated interactions, bearing critical implications in a wide variety of medical conditions ranging from wound healing to cancer metastasis.

Cellular aggregation dictates universal spreading behaviour of a whole-blood drop on a paper strip.

HYPOTHESIS: The complex spreading dynamics of blood on paper matrix is likely to be quantitatively altered with variations in the fractional occupancy of red blood cells in the whole blood (haematocrit). Here, we presented an apparently surprising observation that a finite volume blood drop undergoes a universal time-dependent spreading on a filter paper strip that is virtually invariant with its hematocrit level within physiologically healthy regime, though distinctively distinguishable from the spreading laws of blood plasma and water. EXPERIMENTS: Our hypothesis was ascertained by performing controlled wicking experiments on filter papers of different grades. Spreading of human blood samples of different haematocrit levels ranging between 15% and 51% and the plasma separated from therein were traced by combined high-speed imaging and microscopy. These experiments were complemented with a semi-analytical theory to decipher the key physics of interest. RESULTS: Our results unveiled the exclusive influence of the obstructing cellular aggregates in the randomly distributed hierarchically structured porous pathways and deciphered the role of the networked structures of the various plasma proteins that induced hindered diffusion. The resulting universal signatures of spontaneous dynamic spreading, delving centrally on the fractional reduction in the interlaced porous passages, provide novel design basis for paper-microfluidic kits in medical diagnostics and beyond.

Instrument-free single-step direct estimation of the plasma glucose level from one drop of blood using smartphone-interfaced analytics on a paper strip.

We demonstrated an instrument-free miniaturized adaptation of the laboratory gold standard methodology for the direct estimation of plasma glucose from a drop of whole blood using a low-cost single-user-step paper-strip sensor interfaced with a smartphone. Unlike a majority of the existing glucose meters that use whole blood-based indirect sensing technologies, our direct adaptation of the gold-standard laboratory benchmark could eliminate the possibilities of cross interference with other analytes present in the whole blood by facilitating an in situ plasma separation, capillary flow and colorimetric reaction occurring concomitantly, without incurring additional device complexity or embodiment. The test reagents were dispensed in lyophilized form, and the resulting paper strips were found to be stable over three months stored in a normal freezer, rendering easy adaptability commensurate with the constrained supply chains in extreme resource-poor settings. Quantitative results could be arrived at via a completely-automated mobile-app-based image analytics interface developed using dynamic machine learning, obviating manual interpretation. The tests were demonstrated to be of high efficacy, even when executed by minimally trained frontline personnel having no special skill of drawing precise volume of blood, on deployment at under-resourced community centres having no in-built or accessible healthcare infrastructure. Clinical validation using 220 numbers of human blood samples in a double-blinded manner evidenced sensitivity and specificity of 98.11% and 96.7%, respectively, as compared to the results obtained from a laboratory-benchmarked biochemistry analyser, establishing its efficacy for public health and community disease management in resource-limited settings without any quality compromise of the test outcome.

Smartphone-Integrated Label-Free Rapid Screening of Anemia from the Pattern Formed by One Drop of Blood on a Wet Paper Strip.

Screening of anemic patients poses demanding challenges in extreme point-of-care settings where the gold standard diagnostic technologies are not pragmatic and the alternative point-of-care technologies suffer from compromised accuracy, prohibitive cost, process complexity, or reagent stability issues. As a disruption to this paradigm, here, we report the development of a smartphone-based sensor for rapid screening of anemic patients by exploiting the patterns formed by a spreading drop of blood on a wet paper strip wherein blood attempts to displace a more viscous fluid, on the porous matrix of a paper, leading to "finger-like" projections at the interface. We analyze the topological features of the pattern via smartphone-enabled image analytics and map the same with the relative occupancy of the red blood cells in the blood sample, allowing for label-free screening and classification of blood samples corresponding to moderate to severe anemic conditions. The accuracy of detection is verified by comparing with gold standard reports of hematology analyzer, showing a strong correlation coefficient (R2) of 0.975. This technique is likely to provide a crucial decision-making tool that obviates delicate reagents and skilled technicians for supreme functionality in resource-limited settings.