Abhishek K. Agarwal

Adaptive liquid microlenses activated by stimuli-responsive hydrogels

Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths, or use external control to adjust the microlens focal length. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape—and hence focal length—of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably, we can use pinned liquid–liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -∞ to +∞ (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies.

Programmable autonomous micromixers and micropumps

Programmable autonomous micromixers and micropumps have been designed and realized via a merger between MEMS and microfluidic tectonics (/spl mu/FT). Advantages leveraged from both fabrication platforms allow for relatively simple and rapid fabrication of these microfluidic components. Nickel (Ni) microstructures, driven by an external rotating magnetic field, are patterned in situ and serve as the microactuators in the devices. /spl mu/FT permits in situ patterning through the use of a step-and-repeat fabrication process known as liquid-phase photopolymerization (LP/sup 3/). LP/sup 3/ is a polymer-based fabrication process tool that offers additional fabrication materials, including responsive hydrogels that expand and contract under different stimuli. Using pH- and temperature-sensitive hydrogels as clutches, autonomous micromixers and micropumps have been fabricated and tested that perform as closed-loop microsystems. The step-and-repeat fabrication process allows pre-programming of the system, like a programmable read-only memory chip, to be sensitive to a desired stimulus. Different Ni blade designs, and pH-sensitive hydrogel geometries and dimensions have been designed and tested to better ascertain their effects on micromixing efficiency and response times of hydrogels (related to the autonomous functionality), respectively. Temperature-responsive hydrogels have allowed for development of temperature-sensitive micromixers and micropumps with applications in areas demanding temperature control. [1498].

Polarity Effect in Electrovibration for Tactile Display

Electrovibration is the tactile sensation of an alternating potential between the human body and a smooth conducting surface when the skin slides over the surface and where the current is too small to stimulate sensory nerves directly. It has been proposed as a high-density tactile display method, for example to display pictographic information to persons who are blind. Previous models for the electrovibration transduction mechanism are based on a parallel-plate capacitor in which the electrostatic force is insensitive to polarity. We present experimental data showing that electrovibratory perceptual sensitivity to positive pulses is less than that for negative or biphasic pulses and propose that this disparity may be due to the asymmetric electrical properties of human skin. We furthermore propose using negative pulses for insulated tactile displays based on electrovibration because their sensory thresholds were found to be more stable than for waveforms incorporating positive pulses

A point-of-care PCR test for HIV-1 detection in resource-limitedsettings

A low-cost, fully integrated sample-to-answer, quantitative PCR (qPCR) system that can be used for detection of HIV-1 proviral DNA in infants at the point-of-care in resource-limited settings has been developed and tested. The system is based on a novel DNA extraction method, which uses a glass fiber membrane, a disposable assay card that includes on-board reagent storage, provisions for thermal cycling and fluorescence detection, and a battery-operated portable analyzer. The system is capable of automated PCR mix assembly using a novel reagent delivery system and performing qPCR. HIV-1 and internal control targets are detected using two spectrally separated fluorophores, FAM and Quasar 670. In this report, a proof-of-concept of the platform is demonstrated. Initial results with whole blood demonstrate that the test is capable of detecting HIV-1 in blood samples containing greater than 5000 copies of HIV-1. In resource-limited settings, a point-of-care HIV-1 qPCR test would greatly increase the number of test results that reach the infants caregivers, allowing them to pursue anti-retroviral therapy.

Integration of polymer and metal microstructures using liquid-phase photopolymerization

In this paper we demonstrate, using a fabrication technique, liquid-phase photopolymerization (LP3) for the relatively fast and low-cost integration of thick polymers and electroformed metal microstructures to develop a range of microfluidic components and systems. Liquid-phase UV-photosensitive polymers, similar to negative-tone photoresists, are used to create both polymer microstructures and molds to define electroformed metal (here, nickel—Ni) microstructures. This fabrication process can act as a stand-alone or appended one; it is gentle to allow processing after a metal structure has been released since fabrication occurs only at designated areas on a substrate, i.e. no spinning/casting of photosensitive materials, and self-planarization is achieved since photopolymerization of polymers occurs in the liquid phase. Photopatterned polymer and electroformed Ni microstructures are fabricated using LP3 with a low-end (low-cost) lithographic system. A variety of functional microfluidic components and systems, e.g., an active and a passive chaotic micromixer, and gear trains, are fabricated by utilizing a sequential step-and-repeat LP3 process to demonstrate the integration of polymers and metals.

Autonomously-triggered microfluidic cooling using thermo-responsive hydrogels

We present autonomously-triggered on-chip microfluidic cooling devices that utilize thermo-responsive hydrogels to adapt to local environmental temperatures. An external rotating magnetic stirrer couples with an in situ fabricated nickel impeller in these centrifugal-based microfluidic cooling devices to recirculate cooler water. Temperature-responsive hydrogels, which exhibit volumetric expansion and contraction, are integrated at the axle of the impeller. In this design, the hydrogels behave similar to an automotive clutch, to autonomously control the impellers rotation as a function of the local environmental temperature. Therefore, the hydrogels act as both sensors and actuators and help take away the necessity for additional temperature sensing, feedback, and/or control units here. Cooling devices capable of on-chip thermal management at multiple predetermined onset operation points are realized by changes to the composition of hydrogel to alter its lowest critical solution temperature (LCST). Furthermore, the effect of magnetic stirrer frequency on the fluid cooling and flowrates for different two-blade nickel impeller designs are presented.

Purification of HIV RNA from serum using a polymer capture matrix in a microfluidic device

In this report, we demonstrate the purification of DNA and RNA from a 10% serum sample using an oligonucleotide capture matrix. This approach provides a one-stage, completely aqueous system capable of purifying both RNA and DNA for downstream PCR amplification. The advantages of utilizing the polymer capture matrix method in place of the solid-phase extraction method is that the capture matrix eliminates both guanidine and the 2-propanol wash that can inhibit downstream PCR and competition with proteins for the binding sites that can limit the capacity of the device. This method electrophoreses a biological sample (e.g., serum) containing the nucleic acid target through a polymer matrix with covalently bound oligonucleotides. These capture oligonucleotides selectively hybridize and retain the target nucleic acid, while the other biomolecules and reagents (e.g., SDS) pass through the matrix to waste. Following this purification step, the solution can be heated above the melting temperature of the capture sequence to release the target molecule, which is then electrophoresed to a recovery chamber for subsequent PCR amplification. We demonstrate that the device can be applied to purify both DNA and RNA from serum. The gag region of HIV at a starting concentration of 37.5 copies per microliter was successfully purified from a 10% serum sample demonstrating the applicability of this method to detect viruses present in low copy numbers.

A hybrid natural/artificial electrostatic actuator for tactile stimulation

Two modes of tactile communication have been previously explored-electrocutaneous and electrostatic. The electrostatic mode has the significant advantage of not passing electrical current into tissue to effect stimulation of afferent touch nerves. In previous research, we microfabricated electrostatic tactile displays on a 4-inch wafer using standard clean room processing. Tactile perception studies performed on those showed that subjects could discriminate simple spatial geometric patterns. The focus of the current work is to develop a better understanding of the basic mechanism of perception (activation of receptors) during electrostatic stimulation at the skin-display interface. Three displays were constructed with polyimide (PI) dielectric layers of varying thickness. Studies were performed on human subjects to determine the dependence of threshold of sensation on the PI thickness using both the method of limits and two-alternate forced-choice techniques. The theoretical model for the behavior of the interface (a parallel-plate capacitor) suggests a linear relationship between voltage and dielectric thickness. However, our results indicate that the thickness has little or no effect on the threshold. The results are promising in that they may provide an indirect estimate of the depth of the subcutaneous conductive layer of the skin, and a better understanding of the interface.

Dissolvable membranes as sensing elements for microfluidics based biological/chemical sensors

We demonstrate a chemical and biological sensing mechanism in microfluidics that transduces chemical and biological signals to electrical signals with large intrinsic amplification without need for complex electronics. The sensing mechanism involves a dissolvable membrane separating a liquid sample chamber from an interdigitated electrode. Dissolution of the membrane (here, a disulfide cross-linked poly(acrylamide) hydrogel) in the presence of a specific target (here, a reducing agent-dithiothreitol) allows the target solution to flow into contact with the electrode. The liquid movement displaces the air dielectric with a liquid, leading to a change (open circuit to approximately 1 kOmega) in the resistance between the electrodes. Thus, a biochemical event is transduced into an electrical signal via fluid movement. The concentration of the target is estimated by monitoring the difference in dissolution times of two juxtaposed sensing membranes having different dissolution characteristics. No dc power is consumed by the sensor until detection of the target. A range of targets could be sensed by defining membranes specific to the target. This sensing mechanism might find applications in sensing targets such as toxins, which exhibit enzymatic activity.

An on-chip autonomous microfluidic cooling system

An on-chip self-contained autonomous microfluidic cooling system, driven by a constant external rotating magnetic stirrer, has been developed using liquid-phase photopolymerization and nickel electroplating. A temperature-sensitive hydrogel, that acts in a way similar to an automotive clutch, provides the autonomous functionality. By controlling the rotation of the nickel impeller, the hydrogel effectively controls the pumping of cold water to cool the system when temperatures are high. Once cooled, the system autonomously stops pumping. The autonomous functionality and cooling effect of the system were observed at various heater temperature setpoints. Cooling temperatures ranging between 1.6/spl deg/C and 4.0/spl deg/C were exhibited by the system.