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Biomedical subjects

Arun Majumdar

Publications and source records attributed to Arun Majumdar.

At least 19 recordsLinked to original sources
PubMed2006

Nanomechanical detection of DNA melting on microcantilever surfaces.

We observe surface stress changes in response to thermal dehybridization, or melting, of double-stranded DNA (dsDNA) oligonucleotides that are grafted on one side of a microcantilever beam. Changes in surface stress occur when one complementary DNA strand melts and diffuses away from the other, resulting in alterations of the electrostatic, counterionic, and hydration interaction forces between the remaining neighboring surface-grafted DNA molecules. We have been able to distinguish changes in the melting temperature of dsDNA as a function of salt concentration and oligomer length. This technique also highlights differences between surface immobilized and solution DNA melting dynamics, which allows us to better understand the stability of DNA on surfaces. The transduction of phase transitions into a mechanical signal is ubiquitous for DNA, making cantilever-based detection a widely useful and complementary alternative to calorimetric and fluorescence measurements.

DNA↗
PubMed2006

Point-of-care biosensor systems for cancer diagnostics/prognostics.

With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments--DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.

Biomarkers, Tumor↗
PubMed2006

Lithographic techniques and surface chemistries for the fabrication of PEG-passivated protein microarrays.

This article presents a new technique to fabricate patterns of functional molecules surrounded by a coating of the inert poly(ethylene glycol) (PEG) on glass slides for applications in protein microarray technology. The chief advantages of this technique are that it is based entirely on standard lithography processes, makes use of glass slides employing surface chemistries that are standard in the microarray community, and has the potential to massively scale up the density of microarray spots. It is shown that proteins and antibodies can be made to self-assemble on the functional patterns in a microarray format, with the PEG coating acting as an effective passivating agent to prevent non-specific protein adsorption. Various standard surface chemistries such as aldehyde, epoxy and amine are explored for the functional layer, and it is conclusively demonstrated that only an amine-terminated surface satisfies all the process constraints imposed by the lithography process sequence. The effectiveness of this microarray technology is demonstrated by patterning fluorescent streptavidin and a fluorescent secondary antibody using the well-known and highly specific interaction between biotin and streptavidin.

Adsorption↗
PubMed2006

Thermal conductivity reduction and thermoelectric figure of merit increase by embedding nanoparticles in crystalline semiconductors.

Atomic substitution in alloys can efficiently scatter phonons, thereby reducing the thermal conductivity in crystalline solids to the "alloy limit." Using In0.53Ga0.47As containing ErAs nanoparticles, we demonstrate thermal conductivity reduction by almost a factor of 2 below the alloy limit and a corresponding increase in the thermoelectric figure of merit by a factor of 2. A theoretical model suggests that while point defects in alloys efficiently scatter short-wavelength phonons, the ErAs nanoparticles provide an additional scattering mechanism for the mid-to-long-wavelength phonons.

Journal Article↗
PubMed2006

Intracellular transport dynamics of endosomes containing DNA polyplexes along the microtubule network.

We have explored the transport of DNA polyplexes enclosed in endosomes within the cellular environment by multiple particle tracking (MPT). The polyplex-loaded endosomes demonstrate enhanced diffusion at short timescales (t<7 s) with their mean-square displacement (MSD) Deltax(t)2 scaling as t1.25. For longer time intervals they exhibit subdiffusive transport and have an MSD scaling as t0.7. This crossover from an enhanced diffusion to a subdiffusive regime can be explained by considering the action of motor proteins that actively transport these endosomes along the cellular microtubule network and the thermal bending modes of the microtubule network itself.

Biological Transport, Active↗
PubMed2006

Chemomechanics of surface stresses induced by DNA hybridization.

When biomolecular reactions occur on one surface of a microcantilever beam, changes in intermolecular forces create surface stresses that bend the cantilever. While this phenomenon has been exploited to create label-free biosensors and biomolecular actuators, the mechanisms through which chemical free energy is transduced to mechanical work in such hybrid systems are not fully understood. To gain insight into these mechanisms, we use DNA hybridization as a model reaction system. We first show that the surface grafting density of single-stranded probe DNA (sspDNA) on a surface is strongly correlated to its radius of gyration in solution, which in turn depends on its persistence length and the DNA chain length. Since the persistence length depends on ionic strength, the grafting density of sspDNA can be controlled by changing a solution's ionic strength. The surface stresses produced by the reaction of complementary single-stranded target DNA (sstDNA) to sspDNA depend on the length of DNA, the grafting density, and the hybridization efficiency. We, however, observe a remarkable trend: regardless of the length and grafting density of sspDNA, the surface stress follows an exponential scaling relation with the density of hybridized sspDNA.

Base Sequence↗
PubMed2006

Interpretation of stochastic events in single molecule conductance measurements.

The electrical conductance of a series of thiol-terminated alkanes, (1,6-hexanedithiol (HDT), 1,8-octanedithiol (ODT), and 1,10-decanedithol (DDT)) was measured using a modified scanning tunneling microscope break junction technique. The interpretation of data obtained in this technique is complicated due to multiple effects such as microscopic details of the metal-molecule junctions, superposition of tunneling currents, and conformational changes in the molecules. A new method called the last-step analysis (LSA) is introduced here to clarify the contribution of these effects. In direct contrast to previous work, LSA does not require any data preselection, making the results less subjective and more reproducible. Finally, LSA was used to obtain the conductance of single molecules (HDT, (3.6 x 10(-4))G(o); ODT, (4.4 x 10(-5))G(o); DDT, (5.7 x 10(-6))G(o)). The tunneling decay parameter (beta) was calculated, and it was found to be approximately 1.0 per carbon atom.

Alkanes↗
PubMed2006

Diffusion-limited patterning of molecules in nanofluidic channels.

Diffusion-limited patterning (DLP) is a new technique that enables patterning of labile molecular species in solution phase onto surfaces that are not easily accessible. This technique is self-aligning and is simple to implement for patterning multiple species. We demonstrated DLP by patterning alternating bands of fluorescently labeled and unlabeled streptavidin in biotin-functionalized nanofluidic channels with spatial resolution better than 1 microm. The methodology of DLP also enables experimental measurement of a unique parameter that relates molecular surface grafting density, concentration, diffusivity, and channel geometry.

Crystallization↗
PubMed2005

Mixing crowded biological solutions in milliseconds.

In vitro studies of biological reactions are rarely performed in conditions that reflect their native intracellular environments where macromolecular crowding can drastically change reaction rates. Kinetics experiments require reactants to be mixed on a time scale faster than that of the reaction. Unfortunately, highly concentrated solutions of crowding agents such as bovine serum albumin and hemoglobin that are viscous and sticky are extremely difficult to mix rapidly. We demonstrate a new droplet-based microfluidic mixer that induces chaotic mixing of crowded solutions in milliseconds due to protrusions of the microchannel walls that generate oscillating interfacial shear within the droplets. Mixing in the microfluidic mixer is characterized, mechanisms underlying mixing are discussed, and evidence of biocompatibility is presented. This microfluidic platform will allow for the first kinetic studies of biological reactions with millisecond time resolution under conditions of macromolecular crowding similar to those within cells.

Biocompatible Materials↗
PubMed2005

Polarity switching and transient responses in single nanotube nanofluidic transistors.

We report the integration of inorganic nanotubes into metal-oxide-solution field effect transistors (FETs) which exhibit rapid field effect modulation of ionic conductance. Surface functionalization, analogous to doping in semiconductors, can switch the nanofluidic transistors from p-type to ambipolar and n-type field effect transistors. Transient study reveals the kinetics of field effect modulation is controlled by ion-exchange step. Nanofluidic FETs have potential implications in subfemtoliter analytical technology and large-scale nanofluidic integration.

Electric Conductivity↗
PubMed2005

Characterization of grafting density and binding efficiency of DNA and proteins on gold surfaces.

The surface grafting density of biomolecules is an important factor for quantitative assays using a wide range of biological sensors. We use a fluorescent measurement technique to characterize the immobilization density of thiolated probe DNA on gold and hybridization efficiency of target DNA as a function of oligonucleotide length and salt concentration. The results indicate the dominance of osmotic and hydration forces in different regimes of salt concentration, which was used to validate previous simulations and to optimize the performance of surface-stress based microcantilever biosensors. The difference in hybridization density between complementary and mismatched target sequences was also measured to understand the response of these sensors in base-pair mismatch detection experiments. Finally, two different techniques for immobilizing proteins on gold were considered and the surface densities obtained in both cases were compared.

Base Pair Mismatch↗
PubMed2005

Electrostatic control of ions and molecules in nanofluidic transistors.

We report a nanofluidic transistor based on a metal-oxide-solution (MOSol) system that is similar to a metal-oxide-semiconductor field-effect transistor (MOSFET). Using a combination of fluorescence and electrical measurements, we demonstrate that gate voltage modulates the concentration of ions and molecules in the channel and controls the ionic conductance. Our results illustrate the efficacy of field-effect control in nanofluidics, which could have broad implications on integrated nanofluidic circuits for manipulation of ions and biomolecules in sub-femtoliter volumes.

Electrochemistry↗
PubMed2005

Effects of biological reactions and modifications on conductance of nanofluidic channels.

Conductance characteristics of nanofluidic channels (nanochannels) fall into two regimes: at low ionic concentrations, conductance is governed by surface charge while at high ionic concentrations it is determined by nanochannel geometry and bulk ionic concentration. We used aminosilane chemistry and streptavidin-biotin binding to study the effects of surface reactions on nanochannel conductance at different ionic concentrations. Immobilization of small molecules such as aminosilane or biotin mainly changes surface charge, affecting conductance only in the low concentration regime. However, streptavidin not only modifies surface charge but also occludes part of the channel, resulting in observable conductance changes in both regimes. Our observations reflect the interplay between the competing effects of charge and size of streptavidin on nanochannel conductance.

Biotin↗
PubMed2005

DNA translocation in inorganic nanotubes.

Inorganic nanotubes were successfully integrated with microfluidic systems to create nanofluidic devices for single DNA molecule sensing. Inorganic nanotubes are unique in their high aspect ratio and exhibit translocation characteristics in which the DNA is fully stretched. Transient changes of ionic current indicate DNA translocation events. A transition from current decrease to current enhancement during translocation was observed on changing the buffer concentration, suggesting interplay between electrostatic charge and geometric blockage effects. These inorganic nanotube nanofluidic devices represent a new platform for the study of single biomolecule translocation with the potential for integration into nanofluidic circuits.

DNA↗
PubMed2003

Fabrication of silica nanotube arrays from vertical silicon nanowire templates.

A simple thermal oxidation-etching process was developed to translate vertical silicon nanowire arrays into silica nanotube arrays. The obtained nanotubes perfectly retain the orientation of original silicon nanowire arrays. The inner tube diameter ranges from 10 to 200 nm. High-temperature oxidation produces relative thick, rigid, and pinhole-free walls that are made of condensed silica. This method could be useful for fabrication of single nanotube sensors and nanofluidic systems.

Journal Article↗