Welcome to Nagpal Lab

 

Our group works in the broader field of Quantum Biology and Chemistry (QUBIC), developing out-of-the-box ideas for some of the most intriguing problems at the interface of chemistry, physics and biology. In the emerging field of Quantum Biology, we are developing molecular spectroscopy techniques and quantum-confined materials to provide transformative solutions for detection, diagnosis, and therapy. Our work in detection entails development of facile breath sensing, bioimaging, and optical DNA sequencing techniques. These methods utilize volatile biomarkers in human breath as a quick, inexpensive, and non-invasive detection of human health and wellness; use the window of nominal biological transparency I and II, which combined with photon upconversion, can provide a versatile optical bioimaging and detection system; and provide tools for block molecular identification for different biomolecules using optical molecular vibrational spectroscopy. Development of diagnostics techniques in our group comprises of single-molecule Quantum Molecular Sequencing and Quantum Point Contact Sequencing, based on nanoelectronic spectroscopy, towards a combined genomics, transcriptomics, and epigenomics method. In our efforts towards novel precision therapeutics, our group is developing highly-selective nanotherapies using quantum-confined semiconductor nanomaterials, and using precisely tailored molecular interactions in the cellular environment, to develop targeted therapeutics to eliminate multi-drug resistant pathogens and address the burgeoning problem of antimicrobial drug-resistance. This precision medicine model can also be directed towards molecular therapeutics for a range of targeted diseases. Our work in Quantum Chemistry is directed towards novel photon upconversion; developing transformative nanoscale catalysts for solar-fuel generation using selective quantum-confined states of nanomaterials, and other physical phenomenon like hot-carriers; and developing hybrid nano-bio photocatalysts which combine the selective photochemistry of nanoscale inorganic catalysts with selective fuel generation in biological systems.

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Research Highlights

 

Prashant interviewed by France 24 on the group's discovery of quantum dot phototherapy for multidrug-resistant superbugs

 

For Interview skip to 2:50

 

 

Our novel light-activated nanotherapy proves effective against antibiotic-resistant “superbugs”

 

ABC NEWS Denver Chanel 7: Evening News

 

In the ever-escalating evolutionary battle with drug-resistant bacteria, humans may soon have a leg up thanks to adaptive, light-activated nanotherapy developed by researchers at the University of Colorado Boulder.

Antibiotic-resistant bacteria such as Salmonella, E. Coli and Staphylococcus infect some 2 million people and kill at least 23,000 people in the United States each year. Efforts to thwart these so-called “superbugs” have consistently fallen short due to the bacteria’s ability to rapidly adapt and develop immunity to common antibiotics such as penicillin.  

New research from CU-Boulder, however, suggests that the solution to this big global problem might be to think small—very small.

In findings published today in the journal Nature Materials, researchers at the Department of Chemical and Biological Engineering and the BioFrontiers Institute describe new light-activated therapeutic nanoparticles known as “quantum dots.” The dots, which are about 20,000 times smaller than a human hair and resemble the tiny semiconductors used in consumer electronics, successfully killed 92 percent of drug-resistant bacterial cells in a lab-grown culture. 

“By shrinking these semiconductors down to the nanoscale, we’re able to create highly specific interactions within the cellular environment that only target the infection,” said Prashant Nagpal, an assistant professor in the Department of Chemical and Biological Engineering at CU-Boulder and a senior author of the study.

Previous research has shown that metal nanoparticles—created from gold and silver, among other metals—can be effective at combating antibiotic resistant infections, but can indiscriminately damage surrounding cells as well. 

The quantum dots, however, can be tailored to particular infections thanks to their light-activated properties. The dots remain inactive in darkness, but can be activated on command by exposing them to light, allowing researchers to modify the wavelength in order to alter and kill the infected cells.

“While we can always count on these superbugs to adapt and fight the therapy, we can quickly tailor these quantum dots to come up with a new therapy and therefore fight back faster in this evolutionary race,” said Nagpal.

The specificity of this innovation may help reduce or eliminate the potential side effects of other treatment methods, as well as provide a path forward for future development and clinical trials.

“Antibiotics are not just a baseline treatment for bacterial infections, but HIV and cancer as well,” said Anushree Chatterjee, an assistant professor in the Department of Chemical and Biological Engineering at CU-Boulder and a senior author of the study. “Failure to develop effective treatments for drug-resistant strains is not an option, and that’s what this technology moves closer to solving.”

Nagpal and Chatterjee are the co-founders of PRAAN Biosciences, Inc., a Boulder, Colorado-based startup that can sequence genetic profiles using just a single molecule, technology that may aid in the diagnosis and treatment of superbug strains. The authors have filed a patent on the new quantum dot technology.

The new study was co-authored by Colleen Courtney, Samuel Goodman and Jessica McDaniel, all of the Department of Chemical and Biological Engineering at CU-Boulder; and Nancy Madinger of the University of Colorado Anschutz.

The W.M. Keck Foundation and the National Science Foundation supported the research.

Source: University of Colorado Press Release

 

Our lab launches start up company PRAAN Biosciences based on novel Quantum Molecular Sequencing technology

 

Nagpal and Chatterjee labs are the co-founders of PRAAN Biosciences, Inc., a Boulder, Colorado-based startup based on a novel sequencing technology called "Quantum Molecular Sequencing" that can sequence genetic profiles using just a single molecule, technology that may aid in the diagnosis and treatment of superbug strains as well as genetic disorders and cancer. The authors have filed number of patents on the new technology. PRAAN in Sankrit means "life." CU Technology Transfer Office also has recongnized Quantum Molecular Sequencing technology developed by our and Chatterjee lab with the New Inventor of the Year award. We are developing a platform technology for fast, reliable, high-throughput and cost effective single molecule sequencing of nulciec acids.This kind of sequencing is an important step in the developement of new diagnostic tools for personalized medicine, identifying disease biomarkers, and developing novel targets for vaccines and therapy.

 

Nagpal group demonstrates devices that convert invisible infrared radiation, or “heat”, efficiently into visible light

 

More than 30% of the incident radiation from Sun is invisible infrared light, or “heat”, which cannot be absorbed by solar cells designed to convert light into electricity. Converting this infrared radiation efficiently into visible light can significantly increase the efficiency of photovoltaic conversion of sunlight into electricity, and open up avenues for using other waste-heat sources to generate electricity. Moreover, since the infrared light can also penetrate biological tissues, it can also provide a pathway for simple biodetection and bioimaging applications simply by using invisible infrared light sources, instead of ionizing X-rays or other invasive procedures.


The biggest hurdle towards converting “heat” radiation into visible light, known as upconversion, is low efficiency. Intense infrared light from a laser can be easily used to energetically combine two light particles, or photons, into single visible photon or light radiation. However, diffuse sunlight or low intensity infrared sources (intense infrared radiation can damage tissue) have very low upconversion efficiencies, making this process infeasible.


Researchers from Assistant Professor Prashant Nagpal’s group utilized low intensity infrared light to generate quasiparticle Surface Plasmon waves on inexpensive nanofabricated metal chips. While we can all use lenses to focus light, dual nature of light as particle and wave prohibits using simple lenses to focus light beyond their wave-like length scales. These surface plasmon waves can squeeze light into a spot million times smaller than the incident light wavelength volume, thereby focusing diffuse sunlight into a “laser-like” spot on top of metal pyramids. The researchers also placed doped-lanthanide nanoparticles on the pyramid tips, which absorb these infrared waves, and enhanced the transfer of energy to higher energy Erbium levels, which emits the visible radiation. The researchers showed that on these chip scale devices, not only the light intensity gets enhanced into the focused light spot, but these plasmon waves also enhance the transfer of energy to higher energy levels by several-fold, leading to 80 or 100 fold enhancement in emitted visible light! Therefore, this research can open pathways for improving solar energy conversion, imaging infrared radiation, using waste-heat energy sources, and developing new bioimaging techniques using simple infrared light sources.


This research was recently published in journal Nano Letters. Along with Prashant Nagpal, the study was conducted by Chemical Engineering postdoctoral associates Qi Sun (first author) and Vivek Singh, graduate student Josep Ribot, along with colleagues Haridas Mundoor and Ivan Smalyukh in the Physics Department.
For more information, read the article: http://pubs.acs.org/doi/abs/10.1021/nl403383w

 

Nagpal group publishes design of a new selective nanoparticle catalyst for artificial photosynthesis

 


Simultaneous reduction of carbon-dioxide (CO2) and water using sunlight has been an important step in life cycle on earth. This single reaction performed by plants in an energetically frugal, albeit inefficient process, allows simultaneous balance of CO2 gas and energy harvesting from primary source of energy on earth, the Sun. Several strategies are being investigated currently for converting sunlight into viable renewable source of energy, to address the growing emission of greenhouse gases and depleting sources of cheap energy for burgeoning human population. Developing an efficient artificial photosyntheticprocess to carry out simultaneous reduction of CO2 and water can address this issue of rising level of greenhouse gas emission and provide an alternative source of renewable energy. While several research groups have been trying to develop titanium dioxide (TiO2) nanoparticle catalysts, using expensive metals (like platinum) as chemical dopants for obtaining high catalytic activity, lack of insights into energetic pathways governing multi-electron reduction of CO2 into selective fuels has impeded further research.
Researchers from Assistant Professor Prashant Nagpal’s group recently utilized measurements of electronic density of states (DOS) of nanoparticle catalysts, to identify energy levels responsible for photocatalytic reduction of CO2-water in an artificial photosynthetic process. They introduced these desired states in their nanoparticle catalysts, using dopants or semiconductor nanocrystals, and the designed catalysts were used for reduction of CO2 selectively into hydrocarbons, alcohols, or aldehydes. Using their new design strategy, they also demonstrated a new composite nanocatalyst which shows highest selectivity for hydrocarbon solar fuels (ethane here, >70% selectivity), and high catalytic activity. They also demonstrated that their inexpensive nanocatalyst (4.3% internal quantum efficiency) outperforms platinum-doped TiO2 nanoparticles (2.1%), using a small solar concentrator (4 X solar radiation). Their study can have important implications for development of new inexpensive photocatalysts with tuned activity and selectivity.
This research was recently published in journal Nano Letters. Along with Prashant Nagpal, the study was conducted by Chemical Engineering postdoctoral associate Vivek Singh, and graduate students Ignacio Beltran (co-first author) and Josep Ribot. Prashant’s recent NSF CAREER Award will support further development of other nanoparticle catalysts for making selective solar fuels.

For more information, read the article: http://pubs.acs.org/doi/abs/10.1021/nl403783d
 

Nagpal group demonstrates novel air-gating and chemical-gating in hollow semiconductor nanotubes: From novel breath sensing to new nanoscale semiconductor devices

 

Using TiO2 semiconductor as an important candidate for power electronics, hollow nanotube devices made by Nagpal group showed a tunable rectification factor (transistor ON/OFF ratio or Iforward bias/Ireverse bias) from 1-1000 by simply changing the air pressure! Using chemical-gating, they reversibly altered the conductivity of nanoscaled semiconductor nanotubes (10nm-500nm TiO2 nanotubes) by 6 orders of magnitude, with tunable rectification factor ranging from 1 to1,000,000. They also show that this orders-of-magnitude change in rectifying behavior occurs due to the tunability of the depletion widths in these thin oxide nanotubes by adsorption of water-vapor, and interesting transitions in charge transport behavior. This first demonstration of “air-gating”, “chemical-gating”, “chemical transistors” and “chemical diodes” opens up new and exciting possibilities from multinanalyte breath sesnsing to added dimensionality (4-D transistors) for control over transistor properties (source-drain voltage, field-effect of voltage gating, and chemical gating using composition and concentration of vapor), with fundamental insights into tunable depletion widths, and two-dimensional charge conduction in these important widebandgap semiconductor nanotube materials. Breathing is one of the most essential biological function, far surpassing any other existential human needs like food and water. It also offers an unparalleled insight into human health and wellness by providing access to volatile biomarkers, not readily identifiable in any other clinical diagnostic methods like blood or urine. Furthermore, attributes like non-invasive, safe and painless, easily repeatable and potential for quick and inexpensive point-of-care diagnosis makes breath sensing an attractive method.

Caption: Air-gating (left) and chemical-gating (right) observed in hollow TiO2 semiconductor nanotube devices.

Can Moore’s Law make a comeback?
New research on hollow semiconductor nanotubes offers hope


Several independent analyses have now pronounced: “Moore’s law is dead”, almost 50 years since its inception. While there are very few people who disagree that we have reached the limit of miniaturization of two-dimensional semiconductor circuits, there may be hope for extending, and even perhaps reviving the Moore’s Law (or a newer version of it), by stacking transistors in the third dimension. Intel’s 3D fin design for processors shows that some of the undesirable effects of nanoscale miniaturization in electronic devices like high leakage current and reduction in rectification factor of transistors can be addressed by spatial extension in the third dimension. This also opens up a new dimension (literally!) by stacking planar semiconductor devices and increasing the density of transistors per unit volume. Recent research from Nagpal group suggests that there can be new advantages in adopting novel semiconductor architectures in 3D. They recently showed that the large surface areas in these nanoscaled devices can now be utilized to tune the electronic properties of these semiconductors, and using new physical properties as a result of tailored surface interactions. While most semiconductor devices rely on two-degrees of electronic control (semiconductor channel bias and gate voltage), they have added a new dimension by showing novel “air-gating” and “chemical-gating” in hollow TiO2 semiconductor nanotube devices, and highlight the potential for development of novel 4D transistors (by using channel bias, gate voltage, chemical composition and concentration) using these nanostructures. While demonstrated air- and chemical-gating speeds were slow (~seconds) due to mechanical-evacuation rate and size of their chamber, small nanoscale volume of these hollow semiconductors can enable much higher switching speeds can be achieved with further research, limited by the rate of adsorption/desorption of molecules at semiconductor interfaces (KHz to MHz switching speeds can be obtained). These chemical-gating effects were completely reversible, additive between different chemical compositions, and can enable semiconductor nanoelectronic devices for “chemical transistors”, and very high-efficiency sensing applications. Similar surface tunability and chemical-gating behavior can also be expected in other quasi-one dimensional nanostructures, opening up the possibility of developing functional devices and studying interesting 2D charge conduction properties in these semiconductor nanostructures.