Erik V. Mukerjee

Differential Scanning Calorimeter Based on Suspended Membrane Single Crystal Silicon Microhotplate

This paper introduces an array of single crystal silicon microhotplates for differential scanning calorimetry. Heat transfer analysis considers the tradeoffs between heating and cooling rate, temperature uniformity, and measurement sensitivity, and determines the optimal design for a suspended membrane microhotplate with full backside release. Additionally, considering the requirements of routine sample loading, the size of the square heater (LH) is 100 or 200 mum, while the size of the backside membrane cavity is 400 mum. In the heater region, two interdigitated serpentine doped silicon resistors were designed such that several operational configurations were possible. The hotplates exhibited very high heating efficiency of 36.7 K/mW with LH = 100 mum and 18.3 K/mW with LH = 200 mum while also having time constants on the order of 1 ms. Paraffin wax was mounted on the sensor, and melting was observed when the heater temperature was 55degC with a voltage ramp of 0.2 V/s. With 8 V/s, the paraffin sample was completely consumed within 1 ms with 0.317 mJ of thermal energy extracted. Our design achieves a combination of time constant, temperature sensitivity, and heating efficiency that are comparable or superior to previously published microcalorimeters.

Chemical vapor discrimination using a compact and low-power array of piezoresistive microcantilevers

A compact and low-power microcantilever-based sensor array has been developed and used to detect various chemical vapor analytes. In contrast to earlier micro-electro-mechanical systems (MEMS) array sensors, this device uses the static deflection of piezoresistive cantilevers due to the swelling of glassy polyolefin coatings during sorption of chemical vapors. To maximize the sensor response to a variety of chemical analytes, the polymers are selected based on their Hildebrand solubility parameters to span a wide range of chemical properties. We utilize a novel microcontact spotting method to reproducibly coat a single side of each cantilever in the array with the polymers. To demonstrate the utility of the sensor array we have reproducibly detected 11 chemical vapors, representing a breadth of chemical properties, in real time and over a wide range of vapor concentrations. We also report the detection of the chemical warfare agents (CWAs) VX and sulfur mustard (HD), representing the first published report of CWA vapor detection by a polymer-based, cantilever sensor array. Comparisons of the theoretical polymer/vapor partition coefficient to the experimental cantilever deflection responses show that, while general trends can be reasonably predicted, a simple linear relationship does not exist.

Suspended Membrane Single Crystal Silicon Micro Hotplate for Differential Scanning Calorimetry

This paper introduces an array of single crystal silicon micro hotplates for differential scanning calorimetry. Based on heat transfer analysis considering tradeoffs between response time, temperature uniformity, and measurement sensitivity, suspended membrane micro hotplates with full backside release were found to be optimal designs. Due to the requirements of routine sample loading, the size of the heater is 100 or 200 ¿m while the size of the backside membrane cavity is 400 ¿m. Our design achieves a combination of time constant, temperature sensitivity, and heating efficiency that are comparable or superior to previously reported microcalorimeters.

On-chip laser-induced DNA dehybridization.

Detection of pathogens and relevant genetic markers using their nucleic acid signatures is extremely common due to the inherent specificity genomic sequences provide. One approach for assaying a sample simultaneously for many different targets is the DNA microarray, which consists of several million short nucleic acid sequences (probes) bound to an inexpensive transparent substrate. Typically, complex samples hybridize to the microarray and the pattern of fluorescing probes on the microarrays surface identifies the detected targets. In the case of evolving or newly emergent organisms, a hybridization pattern can occur that differs from any previously known sources. When this happens it can be useful to recover the hybridized DNA from the binding locations of interest for sequencing. Here we present the novel utilization of a focused Infrared (IR) laser to heat user-selected spots on the DNA microarray surface, causing only localized dehybridization and recovery of the desired DNA into an elution buffer where it is available for subsequent amplification or sequencing. The introduction of a focused dehybridization method for spots of interest suppresses the amount of background DNA to be analyzed from downstream processes, and should reduce subsequent sequence assembly errors. This technique could also be applied to high-density protein microarrays where the desire to locally heat spots for release of bound molecules is desired.

Controlled placement of multiple CNS cell populations to create complex neuronal cultures

In vitro brain-on-a-chip platforms hold promise in many areas including: drug discovery, evaluating effects of toxicants and pathogens, and disease modelling. A more accurate recapitulation of the intricate organization of the brain in vivo may require a complex in vitro system including organization of multiple neuronal cell types in an anatomically-relevant manner. Most approaches for compartmentalizing or segregating multiple cell types on microfabricated substrates use either permanent physical surface features or chemical surface functionalization. This study describes a removable insert that successfully deposits neurons from different brain areas onto discrete regions of a microelectrode array (MEA) surface, achieving a separation distance of 100 μm. The regional seeding area on the substrate is significantly smaller than current platforms using comparable placement methods. The non-permanent barrier between cell populations allows the cells to remain localized and attach to the substrate while the insert is in place and interact with neighboring regions after removal. The insert was used to simultaneously seed primary rodent hippocampal and cortical neurons onto MEAs. These cells retained their morphology, viability, and function after seeding through the cell insert through 28 days in vitro (DIV). Co-cultures of the two neuron types developed processes and formed integrated networks between the different MEA regions. Electrophysiological data demonstrated characteristic bursting features and waveform shapes that were consistent for each neuron type in both mono- and co-culture. Additionally, hippocampal cells co-cultured with cortical neurons showed an increase in within-burst firing rate (p = 0.013) and percent spikes in bursts (p = 0.002), changes that imply communication exists between the two cell types in co-culture. The cell seeding insert described in this work is a simple but effective method of separating distinct neuronal populations on microfabricated devices, and offers a unique approach to developing the types of complex in vitro cellular environments required for anatomically-relevant brain-on-a-chip devices.

Measurement of glutamate in dorsal root ganglion cell culture with integrated electrochemical biosensors

Here we describe the fabrication, testing, and improvement of glutamate sensors in direct contact with dorsal root ganglion cells for short-term tissue culture experiments. To establish the feasibility and utility of placing enzymatic glutamate sensors directly under cells in culture, we address the necessity of increasing sensor sensitivity, increasing sensor lifetime, minimizing disruption of cells in culture, and of the spatial resolution seen with sensors directly under cells based on these results.

Rapid thermal analysis of energetic materials with microfabricated differential scanning calorimeters

This paper introduces a class of single crystal silicon micro-scale differential scanning calorimeters for rapid detection and thermal characterization of energetic materials. The suspended membrane micro hotplates have fast time response and high sensitivity, which enables thermal measurements of melting endotherms and deflagration exotherms in energetic materials such as RDX and TNT. The potential exists for sensitivities in the picogram range with thermal scans in the 10s of milliseconds and controlled thermal cycling faster than 106°C/sec.