Micro Nano Bio Fluidics Unit

Research

MICRO/NANOSCALE INTERFACIAL PHENOMENA:

Our research is focused on the fundamental understanding of the physics of fluid interfaces and technological developments in the area of lab-on-chip for healthcare applications. Our fundamental research is centered on the conception and comprehension of novel micro/nanoscale interfacial phenomena. These phenomena could be caused by innate hydrodynamics or by extrinsic factors like acoustic fields. The core areas of investigation include acoustofluidics, droplets, and capillarity/wetting. The themes include the handling and manipulation of particles, droplets, biological cells, and fluid interfaces as well as the interaction of liquid interfaces with surfaces and deformable structures. Our applied research is dedicated to creating lab-on-chip (LOC) technology for healthcare applications. A LOC platform has been developed for in-situ monitoring of gasotransmitters in blood for early diagnosis of sepsis. Technologies have been developed for the isolation and detection of cancer cells in blood. The focus of our current research is on developing improved technologies for generation of tumor spheroids on chip for drug testing and cancer research. We also aim to understand dynamics of sperm cells and developing technology to sort sperm cells for sex selection in livestock.


Acousto-microfluidics

Acousto-microfluidics which enables handling of particles and fluid interfaces using ultrasonic waves has emerged as a power tool in the recent past due to its inherent nature of gentle, precise and contactless manipulation. Two types of waves, namely bulk and surface acoustic waves can be employed to perform manipulations. Bulk acoustic waves (BAW) can be generated using piezoelectric transducers. Bulk acoustic standing waves can be produced in a channel using a piezoelectric actuator bonded to the device and by adjusting the frequency of the wave generated with respect to the channel dimensions. Surface Acoustic waves (SAW) can be generated using an array of interdigitated electrodes patterned on a piezoelectric substrate at an appropriate frequency related to the gap between the electrodes. Both travelling surface acoustic waves (TSAW) and standing surface acoustic waves (SSAW) can be employed for the manipulation of particles and fluid interfaces.


Transition between stream and droplet regimes in a coflow is typically achieved by adjusting the capillary numbers  (Ca) of the phases. Remarkably, we experimentally evidence a reversible transition between the two regimes by controlling exposure of the system to acoustic standing waves, with  Ca fixed. By satisfying the ratio of acoustic radiation force to the interfacial tension force, Ca_ac>1, experiments reveal a reversible stream-drop transition for Ca<1, and stream relocation for Ca≥1. We explain the phenomenon in terms of the pinching, advection, and relocation timescales and a transition between convective and absolute instability from a linear stability analysis. The technique offers means of tuning from stream to droplet mode on-demand, which can find applications in microfluidics, emulsification, and encapsulation.


We provide improved understanding of acoustic focusing of dense suspension (φ>10%) in a microchannel exposed to acoustic standing wave using theoretical model and experiments. The model is based on the theory of interacting continua and utilizes momentum transport equation for the mixture, continuity equation, and transport equation for the solid phase. The model demonstrates the interplay between acoustic radiation and shear induced diffusion (SID) forces that is critical in the focusing of dense suspensions. Shear induced particle migration model of Leighton and Acrivos, coupled with the acoustic radiation force, is employed to simulate the continuum behaviour of particles. Our study revealed that there is a competition between acoustic radiation and shear induced diffusion forces that gives rise to an equilibrium width w of focused stream of particles at some distance Leq along the flow direction. We show that the equilibrium width is governed by Péclet number Pe and Strouhal number St while the length required to obtain the equilibrium focused width depends on the Strouhal number St. 

We investigated irreversible Cassie-Wenzel (C-W) transition on a nanostructured superhydrophobic surface employing surface acoustic wave (SAW) vibration. The transition is achieved upon penetration of the liquid into the nanogrooves driven by the inertial energy of the drop imparted by the SAW. However, the filling up of nanopores imposes energy barrier (Eb) to the transition that requires the displacement of the initial solid-air interface inside the pores with a solid-liquid interface. We unravel that the relative magnitudes of the input acoustic energy (Eac) and this energy barrier dictates the wetting transition; the irreversibility in the transition therefore being explained from energy minimization of the system following the transition. In addition, observing the dynamics of the wetting front allowed the different regimes of the wetting transition process to be identified.


We investigate aggregation of a dense suspension of particles in a PDMS microwell by employing surface acoustic wave (SAW) microcentrifugation via acoustic streaming. Rapid particle aggregation can then be affected in the microcentrifugation flow, arising as a consequence of the interplay between the hydrodynamic pressure gradient responsible for the migration of particles to the center of the microwell and shear induced diffusion force  that opposes their aggregation. Herein, we experimentally investigated the combined effect of the particle size  and sample concentration  on these microcentrifugation flows. The experimental results show that particles of smaller size and lower sample concentration are concentrated efficiently into an equilibrium spot, whose diameter scales with the initial particle volume fraction. In contrast, we found that as the local particle volume fraction at the center of the microwell approaches  the dense limit such that Fsid>Fp, the particle aggregation fails. We also investigate the effects of well diameter, and height, position of microwell and liquid volume on microcentrifugation.


Wetting and Capillarity

We report a simple, inexpensive and rapid method for fabrication of a stable and transparent superhydrophobic (TSHB) surface and its reversible transition to a transparent superhydrophilic (TSHL) surface. We provide a mechanistic understanding of the superhydrophobicity and superhydrophilicity and the reversible transition. The proposed TSHB surface was created by candle sooting a partially cured n-hexane+PDMS surface followed by washing with DI water. The nano/microscopic grooved structures created on the surface conforms Cassie – Baxter state and thus gives rise to superhydrophobicity (water contact angle (161°). The TSHB surface when subjected to oxygen plasma develops –OH bonds on the surface thus gets transformed into a TSHL surface (WCA<1º). Both surface chemistry and surface morphology play important roles for the superhydrophobic to superhydrophilic transition. In the Cassie – Baxter relation for a composite surface, due to the capillary spreading of liquid in the nano/micro grooves, thus giving rise to complete wetting. Rapid recovery of superhydrophobicity from superhydrophilicity was achieved by heating the TSHL surface at 150ºC for 30 min, due to a much faster adsorption of the –OH bonds into the PDMS. Thus it is possible to achieve reversible transition from TSHB to TSHL and vice versa by exposing to oxygen plasma and heat, respectively.


We show that adjacent liquid droplets exhibit long-range attraction and repulsion on an immiscible liquid impregnating a surface when either the drop or the impregnating liquid is volatile. Remarkably, we find that at small times the interaction is attractive, analogous to the “Cheerios effect” but at large times the interaction becomes repulsive depictingthe “Reverse-Cheerios effect”. Our study reveals that the interaction is underpinned by wetting and capillarity, buoyancy and evaporation phenomena. We experimentally observe the interaction between a pair of droplets and provide a theoretical framework to quantitatively predict their transport behaviour. The transition from the Cheerios to reverse-Cheerios effect occurs at a critical time that depends on the ratio of droplet size to the initial interdistance and relative humidity. We showed that by controlling the dispense time and location of the second droplet, only repulsion or attraction leading to coalescence can be achieved. A pair of evaporative droplets on a non-evaporative hydrophobic liquid surface showed only Cheerios effect (attraction) leading to coalescence.  


Transport of droplets on surfaces is important for a variety of applications such as micro liquid handling and biochemical assays. Here, we report evaporation-induced attraction, chasing and repulsion between a target pure aqueous (water) droplet and a driver aqueous mixture droplet comprising water and a lower surface tension and lower vapour pressure liquid on a high energy surface. It is observed that for a fixed concentration of mixture droplet, attraction/chasing or repulsion can be achieved by varying the relative time instants at which the drops are dispensed. Our study reveals that if the water droplet is dispensed within a critical time after dispensing the mixture droplet, the latter will get attracted to and chase the water droplet. On the other hand, if the water droplet is dispensed after this critical time, then it would get repelled from the mixture droplet. We explain the underlying mechanisms that govern the phenomena and demonstrate continuous transport of liquid/cell sample droplets/plugs. The underlying mechanisms were illustrated and a theoretical model was used to estimate the evaporation-induced surface tension-based driving force and the contact line pinning force thus justifying droplet motion. We then exploited the proposed technique for continuous transport of a water/sample droplets which opens up avenue for future explorations involving biochemical applications.


HEALTHCARE TECHNOLOGY:

Sepsis diagnosis

Early detection of systemic inflammatory response syndrome (SIRS) helps in managing sepsis and minimizing its adverse effects in patients. Gaseous signaling molecules, also referred to as gasotransmitters, play a vital role in the process of inflammation. The concentration of these compounds gives crucial information about the state of inflammation. Thus, the change in the level of such gasotransmitters in patients’ blood is a prognostic marker of sepsis. We have developed a microfluidic device that utilizes fluorimetry for the continuous monitoring of the concentration of different gasotransmitters such as H2S, H2O2 , NO and CO in patients’ blood. We have also integrated the optofluidic detection device with a microfluidic plasma separation unit for on-chip blood cell separation and sepsis detection for use in clinical settings.


CTC isolation and genotyping:

Circulating tumor cells (CTCs) occur in very low frequency in whole blood, i.e. 1 mL human blood could contain 1-100 CTCs among few million white blood cells (WBCs) and a billion red blood cells (RBCs). Quantification of CTCs have high clinical value as these cells usually indicate tumor metastasis and facilitate real-time monitoring of systemic therapy by sequential peripheral blood sampling. Molecular characterization of CTCs helps to understand the mechanism of metastasis, enables identifying therapeutic targets and contributes to personalized, anti-metastatic therapies.


LOC for dengue:

Early diagnosis of dengue biomarkers by employing a technology that is less labor- and time-intensive and offers higher sensitivity and lower limits of detection would find great significance in the developing world. We have been developing a biosensor that exploits the localized surface plasmon resonance (LSPR) effect of nanostructures to detect dengue NS1 antigen, which appears as early as the onset of infection. The biosensor integrates a blood-plasma separation to develop lab-on-chip device that facilitates rapid diagnosis (within 30 min) of dengue NS1 antigen from a small volume of whole blood. From 10 µL of whole blood spiked with NS1 antigen, our biosensor reliably detects 0.06 µg/mL of NS1, which lies within the clinical limit observed during the first seven days of infection, with a sensitivity of 9 nm/(µg/mL). These results confirm that the proposed LSPR biosensor can potentially be used in point-of-care dengue diagnostics.


Incubation :

In order to take some of the technologies developed in our lab towards product development and possible commercialization, we have incubated Ariken Labs Pvt. Ltd. Please visit the link for more details.