Shiv Govind Singh

A highly sensitive self assembled monolayer modified copper doped zinc oxide nanofiber interface for detection of Plasmodium falciparum histidine-rich protein-2: Targeted towards rapid, early diagnosis of malaria.

Rapid, ultrasensitive diagnostic/triaging kits for early detection of malarial parasites are critical for prevention of malarial epidemic, especially in developing and tropical countries. Unlike traditional microscopic diagnosis, these kits rely on the detection of antigens specific to malarial parasites. One such antigen which is routinely used in these diagnostic kits is Histidine-rich protein-2; a protein synthesized and released into the blood stream by the parasite Plasmodium falciparum. In this paper, we demonstrate an ultrasensitive nanobiosensor detection platform for Histidine-rich protein-2 having a limit of detection of attogram/ml. This nanobiosensor platform comprises of Mercaptopropylphosphonic acid functionalized copper doped zinc oxide nanofibers synthesized by electrospinning technique. Ultrasensitivity of attogram/ml can be attributed to the complimentary effects of Mercaptopropylphosphonic acid and copper doping in zinc oxide. Mercaptopropylphosphonic acid enhances the functional groups required for immobilizing antibody. Copper doping in zinc oxide not only increases the conductivity of the nanofibers but also pre-concentrates the target analyte onto the Mercaptopropylphosphonic acid treated nanofiber surface due to inherent electric field generated at the copper/zinc oxide heterojunction interface. The impedimetric detection response of copper-doped zinc oxide nanofiber modified electrode shows excellent sensitivity (28.5 kΩ/(gm/ml)/cm(2)) in the detection ranges of 10 ag/ml-10 µg/ml, and a detection limit of 6 attogram/ml. In addition, the proposed biosensor is highly selective to targeted HRP2 protein with a relative standard deviation of 1.9% in the presence of various interference of nonspecific molecules. To the best of our knowledge, this biosensor shows the lowest detection limit of malarial parasites reported in the literature spanning different nanomaterials and different detection mechanisms. Since the nanobiosensor platform is based on immunoassay technique, with a little modification, it can be extended for developing point-of-care diagnostic devices for several biomarkers of importance.

Two-Phase Flow Pressure Drop Characteristics in Trapezoidal Silicon Microchannels

This paper focuses on experimentally studying the pressure drop characteristics for two-phase flow in microchannels of hydraulic diameter 109 mum , over a relatively large range of heat flux of (0-30 W/cm2) and mass flow rate values (44-1114 kg/m2-s). Three fluid flow regimes (single-phase, two-phase, and dryout) have been covered in this paper, with deionized water as the working fluid. For a given heat flux, the variation of average pressure drop with flow rate can be classified into three distinct regimes. In the first regime (higher flow rate), the pressure drop decreases linearly with decrease in flow rate. In the second regime (lower flow rate), pressure drop increases with decreasing flow rate and reaches a maximum (with a minimum on either side). Finally, in the very low flow rate regime, pressure drop increases rapidly with decreasing flow rate. The average pressure drop in the two-phase regime is predicted well by the annular flow model. In addition to absolute pressure drop values, we also report pressure fluctuations. The magnitude of pressure fluctuations appears to be correlated to the underlying flow regime, such as bubbly, slug, and annular regimes, which have been identified through the flow visualization. An important outcome of this study is the identification of as many as four operating points with similar pressure drop penalty. This may help to choose the right operating conditions for a microchannel-based heat sink for use in cooling electronics. These detailed experimental results are also expected to be useful for modeling two-phase flow in microchannels.

One step biofunctionalized electrospun multiwalled carbon nanotubes embedded zinc oxide nanowire interface for highly sensitive detection of carcinoma antigen-125

Ovarian cancer is the most leading cause of cancer-related death in women . The carcinoma antigen-125, which is found on the surface of many ovarian cancer cells is known to be a gold standard clinical biomarker associated with life-threatening gynecological malignancy. In this work, we demonstrate a novel biosensor platform based on multiwalled carbon nanotubes embedded zinc oxide nanowire for the ultrasensitive detection of carcinoma antigen-125. Label free detection of the carcinoma antigen-125 was accomplished by differential voltammetry technique that demonstrated excellent sensitivity (90.14µA/(U/mL)/cm2) with a detection limit of 0.00113UmL-1 concentration. The fabricated immunosensor exhibits good performance with wider detection range (0.001UmL-1-1kUmL-1), reproducibility, selectivity, acceptable stability, and thus is a potential cost-effective methodology for point-of-care diagnosis. The multiwalled carbon nanotubes (MWCNTs) embedded highly oriented zinc oxide (ZnO) nanowires were synthesized by simple, low cost electrospinning technique. Compared to pure ZnO nanowires, electrochemical activity of MWCNTs embedded ZnO nanowires was found to be much higher. The calcination temperature was optimized to avoid any decomposition of the CNTs and to obtain multiwalled carbon nanotubes embedded highly crystalline ZnO nanowires. The salient feature of this biosensing platform is that one step calcination process is enough to create the functional groups on MWCNT-ZnO nanowire surface that are effective for the covalent conjugation of antibody without further surface modification. To the best of our knowledge, this is the first report on MWCNT-ZnO nanowire based immunosensor explored for the detection of cancer biomarker.

An active control strategy for reduction of pressure instabilities during flow boiling in a microchannel

Flow instabilities during boiling in a microchannel have been well studied and documented in the literature. However, passive/active ways to reduce their magnitude are less well explored. In this paper, we examine the effect of external pulsations on flow with respect to reduction in pressure instability during boiling. Both the frequency and the amplitude of superimposed pulsations are varied and the study is performed for different mass flow rates and heat flux values. It is observed that the pressure fluctuations reduce significantly at high frequencies for all the cases studied; however, small frequencies of external pulsations may or may not be helpful. Interestingly, the average pressure is also found to reduce in certain cases. Flow visualization reveals that the flow switches from bubbly to annular when external pulsations are applied, which leads to this reduction in the pressure fluctuation. These results demonstrate that it may be possible to simultaneously reduce both mean and fluctuating pressure drops by carefully choosing the operating parameters.

Electrospun manganese (III) oxide nanofiber based electrochemical DNA-nanobiosensor for zeptomolar detection of dengue consensus primer

Nanoscale biosensors, owing to their high-sensitivity and extremely low limits-of-detection, have enabled the realization of highly complex and sophisticated miniaturized platforms for several important healthcare applications, the most predominant one being disease diagnosis. In particular, nanomaterial facilitated electrochemical detection of DNA hybridization has had an exceptional impact on fields such as genetics and cancerous mutation detection Here we report an ultrasensitive electrochemical platform using electrospun semi-conducting Manganese (III) Oxide (Mn2O3) nanofibers for DNA Hybridization detection. The proposed platform coalesces the inherent advantages of metal-oxide nanofibers and electrochemical transduction techniques, resulting in label-free zeptomolar detection of DNA hybridization. As proof of concept, we demonstrate zeptomolar detection of Dengue consensus primer (limit of detection: 120×10-21M) both in control as well as spiked serum samples. Our reported detection limit is superior in comparison with previously reported electrochemical DNA hybridization sensors for Dengue virus detection, spanning both labeled and label-free transductions. This ultra-sensitivity, we believe, is a result of synthesizing a low bandgap electrospun metal-oxide nanomaterial corresponding to a specific oxidation state of Manganese. This methodology can be extended for detection of any hybridization of interest by simply adapting an appropriate functionalization protocol and thus is very generic in nature.

A simple and novel way of maintaining constant wall temperature in microdevices

Constant wall temperature /homogeneity in wall temperature is the need of various lab-on-chip devices employed in biological and chemical investigations. However method to maintain this condition does not seem to be available. In this work, a novel and simple way of maintaining constant wall temperature is proposed. A diverging microchannel along with conjugate effects is utilized towards this end. Both measurements and three dimensional numerical simulations are undertaken to prove the design. The investigation has been carried out over a large parameter range (divergence angle: 1–8°; length: 10–30 mm; depth: 86–200 μm; solid-to-fluid thickness ratio: 1.5–4.0, and solid-to-fluid thermal conductivity ratio: 27–646) and input conditions (mass flow rate: 4.17 × 10−5 −9.17 × 10−5 kg/s, heat flux: 2.4–9.6 W/cm2) which helped in establishing the finding. It is observed that a nearly constant wall temperature condition can be achieved over a large parameter range investigated. A model to arrive at the design parameter values is also proposed. The method is further demonstrated for series of microchannels where we successfully maintain each station at different temperature within ±1 °C. The finding is therefore significant and can be employed in both single and multi-stage processes such as PCR requiring different constant wall temperature with a fine resolution.

Reliable MOSFET operation using two-phase microfluidics in the presence of high heat flux transients

Randomly generated heat flux transients affect the reliability of advanced integrated circuits and can induce severe nonlinearity in the device response, resulting in the degradation of a gate dielectric in metal oxide field effect transistors (MOSFETs). The effect of high heat flux transients on MOSFET operation and mitigation, using single-phase and two-phase on-chip microfluidics, is reported in this paper. A prototype comprising monolithically integrated MOSFETs, resistance temperature detector (RTD) arrays, simulated transient source (microheaters) and microfluidic networks was developed. The application of a 10 s transient (153 W cm−2) led to the degradation of subthreshold swing (S) from 120 to 240 mV/decade. However, in the presence of water flow, effective mitigation of S (up to 75%) is observed. The rate of mitigation is higher at lower flow rates because of the higher heat-transfer efficiency for two-phase flow. Thus, an appropriate selection of flow parameters can lead to optimized cooling. Additionally, we propose a strategy to localize the transient heat sources based on the temperature profiles generated using an on-chip, distributed RTD sensor array. The proposed methodology can be applied in practical integrated circuits for localization and characterization of heat sources leading to modifications in the circuit design or process integration steps.

Liquid flow through converging microchannels and a comparison with diverging microchannels

Diverging and converging microchannels are becoming an important part of microdevices. In this work, an experimental study of liquid flow through converging microchannels is performed and analyzed using results from 3D numerical simulations. Converging microchannels of various configurations: hydraulic diameter (118–177 µm), length (10–30 mm) and convergence angle (4°–12°) are used to measure the pressure drop for a volume flow rate range of 0.5–5 ml min−1 (8.33 10−6–8.33 10−5 kg s−1) using deionised water as the working fluid. It is observed that the pressure drop in a converging microchannel varies non-linearly with the volume flow rate, and inversely with the convergence angle and hydraulic diameter. An equivalent hydraulic diameter is introduced in order to predict the overall pressure drop through the converging microchannel using the established theory for straight microchannels. The equivalent hydraulic diameter of the converging microchannel lies at 1/3.6th of the total length from the narrowest width of the microchannel; compared with 1/3rd for the diverging microchannel. A comparative analysis of flow through diverging and converging microchannels is also performed. It is shown that fluidic diodicity varies asymptotically with the angle and length of microchannels, whereas it increases with the volume flow rate. A theoretical expression for diodicity is also derived. The maximum fluidic diodicity is found to lie between 1.2 and 1.3. The data presented in this work is of fundamental importance and can help in optimizing the design of various microdevices.

Ultrasensitive, Label Free, Chemiresistive Nanobiosensor Using Multiwalled Carbon Nanotubes Embedded Electrospun SU-8 Nanofibers

This paper reports the synthesis and fabrication of aligned electrospun nanofibers derived out of multiwalled carbon nanotubes (MWCNTs) embedded SU-8 photoresist, which are targeted towards ultrasensitive biosensor applications. The ultrasensitivity (detection in the range of fg/mL) and the specificity of these biosensors were achieved by complementing the inherent advantages of MWCNTs such as high surface to volume ratio and excellent electrical and transduction properties with the ease of surface functionalization of SU-8. The electrospinning process was optimized to precisely align nanofibers in between two electrodes of a copper microelectrode array. MWCNTs not only enhance the conductivity of SU-8 nanofibers but also act as transduction elements. In this paper, MWCNTs were embedded way beyond the percolation threshold and the optimum percentage loading of MWCNTs for maximizing the conductivity of nanofibers was figured out experimentally. As a proof of concept, the detection of myoglobin, an important biomarker for on-set of Acute Myocardial Infection (AMI) has been demonstrated by functionalizing the nanofibers with anti-myoglobin antibodies and carrying out detection using a chemiresistive method. This simple and robust device yielded a detection limit of 6 fg/mL.

Facile non thermal plasma based desorption of self assembled monolayers for achieving low temperature and low pressure Cu–Cu thermo-compression bonding

This paper reports Self Assembled Monolayer (SAM) of propanethiol desorption assisted low temperature, low pressure copper to copper (Cu–Cu) thermo-compression bonding, a technique which could potentially open up a whole new platform for developing next generation heterogeneous smart devices using 3D integrated circuit technology. Thiolated self assembled monolayers protect a freshly deposited copper surface from oxidation and other contamination. Removal of this SAM layer just prior to bonding would potentially bring down temperature and pressure thus rendering the process CMOS compatible. This paper focuses on using Non-Thermal Plasma (NTP) desorption, which is a simple, robust, room temperature technique for desorbing SAMs. The desorption was carried out in an indigenous chamber specifically designed for this purpose. Thermo-compression bonding post desorption resulted in a very good quality bonding with a bond strength of 132 MPa, performed at a relatively low temperature of 200 °C and a low pressure of 5 bar.