Photons as information carriers have revolutionized the field of information and communication technology by faster, uninterrupted and high density data transfer. Silica based fiber optics (SOF) with rare earth (Erbium) doped fiber amplifiers are performing exceptionally well for long range date transmission and processing. Current quest is for the miniaturization of data communication devices to an ultimate lowest dimension have spurred great efforts in reducing the photonic structures and components to a sub micron scale. Polymer optical fibers (POF) are appealing in this aspect which can be extruded into smaller diameters, better mechanical flexibility, easy handling, low cost manufacturing, infrared (long wavelength) transparency, and have great potential for short-distance haul data communication networks. The major limiting factor is the higher attenuation losses in polymer fibers, typically in the order of 100 db km-1. Transmission losses in POF can be reduced by introducing cladding layers with step or graded refractive indices which restrict the out coupling losses however can be overcome in a more efficient way by using amplifiers to counter balance the attenuation. The amplification is attained by stimulated emission occurring in chromophores or active dopants once population inversion is reached and a spectrally matching signal passes through the fibers. In this respect, an optical amplifier can be considered as a lasing system without feedback. Due to high gain over a broad bandwidth in organic chromophores that can be easily incorporate to polymer fibers, makes them suitable for high density short distance haul data transfer networks. Electrospinning is a technically mature and a powerful technique to develop smooth polymer fibers with high aspect ratio and tuneable diameters from ranging tens of nanometers to microns without any high temperature processing (thermal extrusion). Graded as well as step refractive index fibers were easily be prepared by utilizing cladding layers of different refractive indices by co-axial or tri-axial spinning methods. A variety of functional dopants such as dye molecules, quantum dots, nanoparticles can be readily employed to tailor the optical, electrical and magnetic properties of the host nanofibers with great versatility. More interestingly direct writing of nanofibers to desirable patterns and geometries with high degree of precision is possible with near field spinning at reduced voltages. The high surface to volume ratio, possibility of functionalization with various organic receptors for volatile organic compounds, deposition of nano fibers with high precision for integration with optical components makes them suitable candidates for lab on a chip sensing devices.
The key objectives of the project are:
ü Development of electro spun nano fibers with controlled morphology, alignment and core sheath structures with contrast in refractive indices to have minimal/optimal waveguide loses.
ü Development of direct write continuous polymeric nanofibers using low-voltage near-field electro spinning for position-controlled deposition and precise integration of individual fibers with macroscopic optical components.
ü Quantifying and optimizing gain in nanofibers doped with organic dyes, triplet scavenchers for continuous wave operation, noble metals for metal enhanced fluorescence, rare earth nano particles for fluorescence up-conversion.
ü Modulation/switching of the gain in the doped nano-fibers by electric field induced switching in the field effect transistor geometry as well as by optical gating pulses.
ü Integration of single/aligned nanofibers to optical components for the demonstrating of lab on a chip sensing device for volatile organic compounds.
The group is currently working on the standardization of the electrospun fibers in far field by varying the viscoelastic properties of the polymers to incorporate organic dyes and nano-particles (Rare earth and Noble metals). Fluorescence up conversion nano-particles (UNCP) with sodium yitrium tetrafluorate (NaYF4) as the host, Yitterbium (Yb) as sensitizer and Er3+, TM3+ amd Ho3+ as emitters will utilized to have 980/808 nm wavelength excitation. UNCP nanocrystals were prepared by solvo-thermal preparation method and substituting with capping ligands for the compatibility with the polymers employed for spinning. The uniqueness of the project is the controlled deposition of the fibers with desired functionality by the near-field electrospinning method where the fibers are collected at a short distance from the syringe orifice, before the bending instability occurs. The near field electrospinning machine has to be made in the laboratory as the ambitious project requires customization depends on the specific objectives and is currently on its final stage of testing.
Needed to be identified by the scientist
The challenge here is to reduce the diameters from microns to few hundreds to tens of nanometres. The conventional way is to reduce the size of the orifice, however cannot reduce to critical value due to the hindered flow of the viscoelastic polymer solution. The ideal way is to use low voltage, short distance direct write on the substrate and will be implemented to have the control of fiber diameter, deposition rates and positioning. We will also employ co-axial and tri-axial spinnerets as well as co-extrusion to have the control of the refractive indices of the fibers to have low waveguide loses and the fictionalization of the fibers with sensing sites.
25-mer long phosphorodiamidate morpholino oligonucleotides (PMO) are used for gene silencing (Figure 7).
· Currently PMOs are commercially available with Gene Tools LLC, USA and it is their proprietary item and covered by their patent (Gene-Tools US, patent 5,185,444, 1993) (www.gene-tools.com)
· Cost of regular PMO: 300 nmol 400 $ and 20,000 $/gm
· Cost of modified PMO: 400 nmol 700 $
Recent development on PMOs:
Recently FDA gave approval to Sarepta Therapeutics, USA for the use of morpholino-based drug called “Eteplirsen or Exondys 51” for the treatment of Duchenne muscular dystrophy (DMD) and only oligo-based drug. Cost of the treatment of a single child for 1 year is 300000 US$.
Hence PMOs have so much importance and commercial value.
Though the molecule is not new anymore, however, synthesis protocol has not been disclosed in the literature except their patents. Additionally, their delivery is a long standing problem. Therefore, it is a challenge for the scientists to develop independently a synthesis and delivery protocol which is not related to the Gene Tools patented method.
We are the only group to independently develop two methods for the preparation of PMOs. Scientists all over world are relying on our method.
ü Method 1: Chlorophosphoramidate method to synthesize PMO [Current Protocols in Nucl. Acid Chem. 2015, 4.65.1–4.65.26]. We made monomers 1 and 2 upto 10 to 20 gm scale, used for PMO synthesis. These monomers are commercially available with CarboSynth Ltd. UK, and Toronto Research Chemicals (https://www.trc-canada.com/product-detail/?I780735) using our method (Tetrahedron Let. 2012, 53, 6714-6717). Hence these are commercially important.
ü Recently granted patent on modified PMO: Sinha et. al. Morpholino based antisense agent. US 9,914,745B2.
ü Method 2: H-Phosphonate method to make PMOs. (Filed patent and published in Tetrahedron Lett. 2015, 56, 4565–4568). Again H-phosphonate monomers are made in gram scale.
ü Delivery: We have developed Internal oligoguanidinium-based cellular transporter (IGT) for effective delivery of PMOs and IGT conjugated PMO worked well in vitro, zebrafish (Bioconjugate Chem. 2016, 27, 2254–2259) and mice models and is much better than gene tools delivery technique called Vivo PMO w.r.t efficacy and toxicity [Filed patent]. Our method could be useful for the delivery of other antisense reagents also, scale up is necessary and we have already standardized for 5 gram scale synthesis of IGT.
Dystrophy Annihilation Research Trust (DART), Bangalore
ü Morpholino monomers (20 gm scale achieved)
ü Morpholino oligos, (Scale up need to be standardized as we have achieved analytical scale for research purposes)
ü Developed a toxicity free new delivery vehicle (5 gm scale achieved)
ü Morpholino delivery and targeted therapy for DMD, personalized medicine (Scale up need to be standardized).
ü Our delivery vehicle can be used for the delivery of PMO, thioRNA, siRNA, PNA, LNA, peptides and non cell impermeable drugs in the lab research primarily and extended to the development of antisense-based therapy.
We signed a memorandum (vide number: U712552 dated 28.9.2015) of understanding with Environmental research group, R&D, Tata Steel on removal of cyanide and chloride from steel industry waste water to mitigate the wastewater pollutants in order to reduce water consumption and maintain sustainable recycling process.
In the first phase of the project (TSL-1), we initiated a process for capturing free cyanide in steel wastewater containing ~5 ppm free cyanide utilizing one supramolecular cage complex and demonstrated effective complexation of free cyanide in steel wastewater by the “cage complex receptor”. In fact, cage complex receptor (active ingredient) is capable of complexing 70-80% free cyanide in steel wastewater within 10 minutes. This active ingredient had been used to treat Tata Steel wastewater, in lab process. The maximum quantity of the cage complex receptor was synthesized in the laboratory was around 2.0 gm. Thus, the bottle neck of the entire process was lying on the development of large scale production of the “cage complex receptor”.
ü In the second phase of the project entitled “Bench scale development of anion complex (synthetic receptors) for removal of cyanide from steel wastewater” (TSL-2) our objective and deliverable were to synthesize the above cage complex receptor in large scale & its cost optimization and to deliver 1.5 Kg of the material respectively.
ü In the third phase of the project entitled “Modification of Cage Complex Receptor for Cyanide Removal” (TSL-3) our objective is to modify the previously developed “cage complex receptor” towards its high aqueous solubility for more efficient removal of cyanide from steel wastewater and to reduce the cost of the “modified cage receptor complex”.
ü In TSL-2, we have scaled up the production of the cage complex receptor under TRC program and recommend bench/pilot scale production of complex along with production cost optimization.
ü In TSL-3, aqueous solubility of the modified cage complex has been improved significantly (8.00 g/L) as compared to the previous complex, which was sparingly soluble in water. Moreover, this generation complex is found to be cheaper compared to previous complex.
ü In TSL-2, we successfully synthesized cage complex in high yields. Initially, we synthesized the complex in » 2gm/ reaction scale and then scaled it up to » 32 gm/ reaction by maintaining the same reaction time. We had standardized the volume of solvents and other reaction conditions in order to get better yield and low cost of productivity. Finally, we delivered 1.5 Kg of above complex to TATA Steel Ltd. as per our agreement. We also sent the completion report of this project to TATA STEEL LTD. on time. Their evaluation on the completion report is as follows: “Thank you for details technical report, we are highly satisfied with this work and also noted the project has completed in time line.”
ü In TSL-3, laboratory scale modification of the complex towards the development of second generation flocculent or synthesis of simpler cleft bound complexes for complexation of free cyanide in steel wastewater has been demonstrated.
TATA STEEL LTD., Jamshedpur, India
To make the flocculent cost effective to treat waste-water containing free cyanide.
ü Development of an apparatus for atmospheric sensing of trace oxidants at ppb to ppt level, and atmospheric measurements in collaboration with an industrial partner in selected industrially polluted zones.
ü Assessment of some of the key organic and inorganic pollutants in industrial effluent waters and development of methods to suggest remedies for removal of pollutants. Here a key target is cyanide radical, whose permissible limit is less than 0.2 ppt.
ü An apparatus and related patent, and looking for an industrial partner for atmospheric sensing of HONO, the precursor of key atmospheric oxidant OH radical.
ü A methodology for removal of dark colours and pollutants from industrial effluent waters.
ü An equipment based on optical absorption spectroscopy has been developed. The name given to the apparatus is, “Long-path Liquid-core Optical Wave Guide Spectrometer”. Using this apparatus we have been able to measure nitrous acid (HONO) at parts per trillion level in aqueous medium. Using this apparatus, for the first instance, a real time, sensitive and accurate calibration curve has been obtained for atmospheric sensing of HONO at ppt level. The heart of the apparatus is a special Teflon capillary, which when filled with an aqueous solution of the species whose concentration has to be measured acts as an optical waveguide, and offers an effective path length of several hundred meters. In this apparatus we have used a laser diode as a light source, which has been coupled with the waveguide very effectively.
ü A patent application for development of this apparatus has been sent to TIFAC (DST) and further editing of the document based on the feedback of TIFAC is going on. The title of the patent is, “Development of a laser assisted Long-path Liquid-core Optical Guide (LLOG) for ultra-sensitive absorbance measurements”.
ü Two agreements in the form of collaborative projects have been developed with TATA Steel Limited. The aims of those projects are the following.
(i) OH radical treatment for removal of the colorants in the effluent-water of coke plant of TATA Steel and diagnosis.
Project costs (to be funded fully by TISCO): Rs. 15, 99, 000/-
(ii) Assessment of the level of OH radical, the atmosphere’s detergent, in the ground level air of Jamshedpur and suggestive remedies.
Project costs (to be funded fully by TISCO): Rs.17, 69, 520/-
ü Significant progress has been made with respect to the first scheme. We have been able to remove the dark brown color of the effluent water of the coke making plant of TATA Steel Ltd. by treating the water with UV light in presence of trace of hydrogen peroxide. OH radical is produced on photo-dissociation of hydrogen peroxide, and the result in terms of extent of colour removal is shown below using a diagram.
ü In addition to colour removal, the method has been shown to have a dramatic effect on reduction of the toxic cyanide radical in the water. By varying the pH of the effluent during UV treatment in presence of hydrogen peroxide, it has been possible to bring down the CN- radical concentration in water from 15 ppm to below 0.1 ppm.
ü A major scientific issue is to identify the chemicals responsible for the dark colour of the effluent. Some progress has been made in this regard.
ü Major facility: A LC ESI mass spectrometer has been successfully installed.
TATA Steel Ltd., Jamshedpur
Finding a key industrial partner who can develop our invention to a market-ready form.
Global crop yields are reduced up to 40% per year due to pest infestation, which affects the farmers and economy. We have taken major initiative to conserve the crop yield which was widely affected by the plant pests. A unique approach has been established where sex pheromones of certain agricultural pests are detected first. Prior infestation stage is then identified and necessary action can thus be taken by the end-users, i.e. farmers, to manage the pest infestation efficiently.
ü Development of novel cost-effective pheromone nanosensor for early detection of pest infestation
ü Remote monitoring of pest infestation across an agricultural field
ü Validation of the technology at different seasons and environmental conditions across India
ü Smart IoT enabled system for early detection of pest infestation
ü Demonstration of the system on different agricultural and horticultural produce
ü A unique functionalization protocol has been established for the selective and quantitative detection of female sex pheromone of certain agricultural pests by the suitably functionalized MEMS devices.
ü Separate nanosensors were generated for the pests like Helicoverpa armigera, Scirpophaga incertulas and Bactrocera oleae.
ü It has the ability to predict the prior infestation stage in an agricultural field.
ü This recognition of pheromone molecules even before visual onset may alert the farmers to take necessary actions in a localized manner and thus this approach may be efficiently and economically used in agricultural farms to significantly reduce crop and attendant financial losses.
(i) Pheromone nanosensors were generated for the selective and quantitative detection of female sex pheromones of certain agricultural pests like Helicoverpa armigera, Scirpophaga incertulas and Bactrocera oleae.
(ii) The sensors were validated in a confined region in the presence of male and female pests and tomato plants which directly mimics the real environmental conditions.
G K Machineries and Robotics Pvt. Ltd., Bangalore
ü Integration of the pheromone nanosensors with unmanned aerial vehicle (UAV), i.e. Drone.
ü Development of the remote monitoring hardware & software and packaging.
ü Calibration, standardization and demonstration of the nanosensors at different seasons and weather conditions for various agricultural and horticultural produce across India.
Conventional diagnostic practices are time consuming, labor-intensive; require elaborate infrastructures and on-field pathologists. Hence the development of portable, inexpensive point-of-care (POC) diagnostic devices are of high relevance in pharmaco-clinical field. We have taken initiatives to address these public health and diagnosis issues.
ü Development of novel molecules for easier diagnosis of various pathological conditions
ü Development of a medical kit addressing the issue
Point-of-care (POC) diagnostic devices for easy and rapid identification of pathological conditions
ü A novel turn-on probe was developed for easy, rapid and accurate quantification of human serum albumin (HSA), present in different biological fluids, like urine, blood, serum, cerebrospinal fluid and pleural fluid.
ü These bio-fluids were collected from patients suffering with different clinical manifestations.
(i) New turn-on HSA sensitive probe has been developed and validated on different biological fluids, like urine, blood, serum, cerebrospinal and pleural fluids, collected from patients suffering with different clinical conditions like Systemic Lupus Erythematosus (SLE), Type 2 Diabetes Mellitus (T2DM), nephritic syndrome, nephrotic DM, antiphospholipid antibody syndrome (APLS) etc.
ü Cell for IPR Promotion and Management (CIPAM)
ü Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata
ü University of Texas at Arlington, USA
Development of cost effective point-of-care diagnostic device for easier identification of pathological conditions.
Department of Health Research, GOI, suggested establishing a network of laboratories bridging research and applications for reducing the burden of non-communicable diseases, like cancer, from the society. Hence we have taken significant initiatives to address these public health issues.
ü Development of biocompatible and stimuli sensitive vehicles for the efficacious delivery of anticancer drugs and/or genes
ü Demonstration of their efficacy both in vitro and in vivo models
Smart nanomaterial for efficient anticancer drug and/or gene delivery
ü Multi-drugs resistance (MDR) is one of the major challenges faced by the cancer patients during their prolonged chemotherapeutic treatments all over the world.
ü New pH-responsive gemini lipid derived co-liposomes were prepared for the delivery of doxorubicin to the drug resistant cancer cells.
ü New reduction responsive nanovesicles, derived from α-tocopheryl-lipoic acid conjugate, were also developed for the efficacious drug delivery both to the drug-sensitive and drug-resistant cancer cells.
ü New stimuli-sensitive nanomaterials were synthesized.
ü They were demonstrated for the delivery of anticancer drug, doxorubicin, both to the drug-sensitive and drug-resistant cancer cell lines under in vitro conditions.
Needed to be identified by the scientist
Establishing the efficacy of the nanomaterials under in vivo conditions.
ü Designed polymer micelle/nanoparticle for inhibiting amyloid protein aggregation under intra-/extracellular space
ü Designed polymer micelle for clearing toxic amyloid protein aggregates from cell and to increase cell survival
ü Nanodrug formulation for neurodegenerative diseases associated with protein aggregation
Polylactic acid-based designed polymer micelle for inhibiting amyloid protein aggregation: We have synthesized three different poly-L-lactide polymers functionalized with trehalose, dopamine and arginine. Trehalose is selected for its known anti-amyloidogenic property, dopamine is selected for neuronal cell targeting and arginine is selected for direct cell membrane penetration. The polymers have average of ~1500 Da molecular weight and they self-assemble into 50-100 nm particle with trehalose/dopamine/arginine toward outward direction. Different combination of three polymers are used for anti-amyloidgenic activity study in Huntington model neuronal cell (HD150Q). Results show the cell penetrating ability of the polymer nanoparticles, immunoblot experiment reveals efficient lowering of polyglutamine aggregation inside cells and cytotoxicity study show enhanced cell survival against toxic protein aggregates. Comparative study show that nanotrehalose is 200 times efficient that molecular trehalose.
Polyaspartic acid-based designed polymer micelle for clearing amyloid protein aggregates: Clearing of protein aggregates from the brain is a critical issues for the treatment of various neurodegenerative diseases. Although variety of anti-amyloidogenic chemicals/biochemicals are identified for inhibiting such protein aggregation, their performance in clearing of protein aggregates is poor. Here we report a designed biopolymer micelle of 15-30 nm hydrodynamic size that can clear protein aggregates from cell via up-regulated autophagy process. The polymer has polyaspartic acid backbone and functionalized with fatty amine, arginine and primary amine for inducing self-assembly, enhanced cell uptake and up-regulating autophagy processes, respectively. The polymer micelle enters into the cell via lipid raft endocytosis, transported to perinuclear region where protein oligomer/aggregate predominantly localizes, clears aggregated protein from the cell and enhances the cell survival against toxic protein aggregates. The designed polymer micelle may be used as a drug delivery carrier for anti-amyloidogenic drugs for enhanced efficacy in the treatment of neurodegenarative diseases.
ü Designed iron oxide based nano-trehalose with efficient inhibition of protein aggregation in cell model and Huntington mouse model
ü Designed polyaspartic-based nano-green tea with efficient inhibition of protein aggregation in cell model
ü Designed polyaspartic-based micelle with efficient clearing of toxic amyloid protein aggregates from cell.
Needed to be identified by the scientist
ü Designing nanodrug for complete cell survival from toxic protein aggregates and brain targeting of designed nanodrug
ü Increased loading of anti-amyloidogenic polyphenoloc drugs which are water soluble
Alternative resources for commercially available Cell lines for screening laboratory made drugs and delivery vehicles
We isolated tumorigenic primary cells from carcinogen induced mouse tumor tissues with an inexpensive and inhouse method. These cells can be cryopreserved and maintained more than 20 passages. These cells mimic the characteristics of cancer cells and can be used for studying the efficacy of drug treatment and for deciphering the molecular signature.
Successfully, primary tumorigenic cells were stored at -800C/Liq N2 and maintained till passage number 20.
Needed to be identified by the scientist
Trial in human patient of the drugs/delivery vehicle which will be screened in our developed primary tumorigenic cells.
ü Establishing a mild and versatile synthetic method for functional PDS
ü Amphiphilic PDS, drug encapsulation and delivery
ü PDS-drug conjugate(s) for targeted delivery
Amphiphilic polymers are attractive for drug delivery as they exhibit the ability to sequester structurally diverse drug molecules and release them in a desired disease location with response to specific external stimuli. Amongst various stimuli responsive polymers, disulfide containing polymers are particularly appealing as they may be reduced by Glutathione, a tri-peptide over-expressed in cancer cells. Although Glutathione reducible disulfide bond has been used in the past for drug delivery application, in all examples the disulfide bond has been appended to a non-degradable polymer backbone. Furthermore, despite a large number of recent studies highlighting the utility of stimuli responsive amphiphilic polymers in drug delivery and other biological applications, the focus has been mainly limited to chemical properties of the newly synthesized polymers while the impact of physical properties such as rigidity, shape or morphology of the polymeric nanostructures largely remain unknown. To address these issues we have explored synthesis, self-assembly, drug-encapsulation/ conjugation and delivery based on PDS scaffolds.
We have used a simple condensation route (Scheme 1) to develop1-2 a synthetic methodology for functional PDS. Extending the methodology, we have synthesized amphiphilic PDS with different hydrophilic blocks. We have shown contrasting morphology of two ABA type amphiphilic block copolymers3 depending on the nature of the hydrophilic block (A) and its impact on stimuli-responsive targeted drug delivery selectively to the cancer cells. The hydrophobic B block in both the polymers consists of a bio-reducible segmented poly(disulfide) (PDS) while poly-N-isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether-methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively. In aqueous medium, P1 formed polymersome (Dh = 80-100 nm) while P2 exhibited micellar structure (Dh = 30-40 nm) as indicated from small angle neutron scattering (SANS) and transmission electron microscopy (TEM) studies. Both P1 and P2 could encapsulate a hydrophobic dye Nile red (NR) but for a hydrophilic probe Calcein, encapsulation was successful only by P1 confirming the difference in the morphology. This can be attributed to the different packing parameters as the brush like PTEGMA block in P2 occupies a relatively larger volume than the PNIPAM block in P1 and thereby disfavors the polymersome structure. Glutathione (GSH) responsive release profiles not only indicated a substantial effect of the GSH concentration on the release rate but also showed a much faster release of the encapsulated NR from the polymersome (P1) than the polymer micelle (P2). A cancer drug doxorubicin (Dox) could also be efficiently loaded in both P1 and P2 aggregates, while the GSH triggered release exhibited a similar trend that was observed for NR. Size exclusion chromatography indicated that in presence of GSH (20.0 mM), the PDS block in P1 could be fully degraded but not in P2 corroborating with the difference in dye release kinetics between polymersome and polymer micelle. MTT assay with Hela cell revealed outstanding biocompatibility for both the polymers as almost 100 % cells remained alive after treating them with P1 or P2 (C = 500 mg/ ml) for 72h. Also, no lysis of human red blood cells could be noticed in presence of these polymers implying high biocompatibility. Dox-loaded polymers (P1-Dox and P2-Dox) exhibited minimum toxicity to normal cells like C2C12. In contrast, P1-Dox exhibited excellent killing efficiency to the Hela cells (cancer cell) (in which the GSH concentration is known to be significantly higher). However, surprisingly P2-Dox exhibited a much poorer activity even to Hela cells. Fluorescence microscopy studies revealed comparable cellular uptake of P1-Dox and P2-Dox. But the polymersome entrapped dye could escape fast from the cargo and reach the nucleus efficiently, while the drug-loaded micelle still was found to be located in the perinuclear zone explaining the significant difference in their drug delivery performance. However, non-covalent encapsulation suffers from problems of premature drug release and rapid clearance from the bloodstream, lack of desired pharmacokinetic profile and unpredictable fate of the cargo after drug release which limits their in vivo application. Some of these issues have been successfully addressed in covalent polymer-drug conjugates which on the other hand suffer from the synthetic difficulties, incomplete degradation due to the inaccessibility of the degradable linkage in hydrophobic domain and inadequate drug loading efficiency.
We have shown a facile strategy for synthesis of ABA type amphiphilic polymer having a fully bio-reducible hydrophobic poly(disulfide) (PDS) block (B block) with pendant hydroxyl functional groups which could be modified by post-polymerization transformation to conjugate a cancer drug Camptothecin (CPT) (Scheme 2) with remarkably high drug loading content (> 30 %) using a labile carbonate linker.4 The polymer showed spontaneous polymersome assembly in water. Glutathione, a tri-peptide known to be over-expressed in cancer cells, triggered a cascade reaction leading to efficient release of the active drug. It reduced the backbone disulfide bond to produce thiols which by intra-molecular cascade reaction expunged the carbonate linked pro-drug to release it in the active form. The polymeric-prodrug assembly successfully internalized to cancer cell and showed selective killing efficiency with very low IC50 value of 3.1 mg/ mL (better than even the free drug) while it did not show any toxicity to a normal cell upto 300 mg/ mL owing to lack of GSH.
Needed to be identified by the scientist
ü In vivo success
In recent times, materials with good flexibility, high transparency, and low sheet resistance together with efficient EMI shielding and good defrosting capability are highly desirable. This project aims to fabricate metal micromesh structures derived transparent conducting electrodes by means of a novel stencil lithography.
ü Simple and economic fabrication of transparent conducting electrodes (TCEs) on flexible substrate
ü Realizing TCEs with high transmittance and low sheet resistance
ü Transparent conducting thin film with 88% transparency and 3 ohm/sq sheet resistance.
ü Transparent defrosting windows with low power consumption
ü Fabricating flexible and transparent EMI shielding films with superior shielding effectiveness.
ü Simple and low-cost fabrication of high performing TCEs
ü The optoelectronic properties of these TCEs are enriched in many ways relative to the conventional indium tin oxide films.
ü The TCEs demonstrate high transmittance of light in UV, Visible and IR regions
ü The devices are highly stable in air up to few months with hydrophobic protective layer
ü The TCEs demonstrated a remarkably high transparency of 88 %
ü A very low sheet resistance of 3 ohm/sq is attained with these TCEs
ü Mechanical flexibility measurements demonstrated the TCEs are unaffected even after 1000 bending cycles.
ü The fabrication process is scaled up to realized 5 x 5 cm2 area TCEs and demonstrated defrosting application
Interacting with UFlex Limited
ü Decreasing the surface roughness of TCEs.
Optically transparent and mechanically flexible photodetectors are crucial in next generation optoelectronic applications including smart windows and transparent image sensors. Commercially available photodetectors are rigid, brittle, expensive to fabricate and completely opaque thereby restricting their applications in next generation electronics. This project aims to fabricated transparent, flexible and super-hydrophobic photodetectors using a simple, inexpensive and large area scalable method.
ü Fabrication of transparent and flexible photodetectors with high performance
ü Broad band photodetection using band gap engineering
ü Large area photodetectors over 50mm x 50mm size substrate
ü Transparent image sensors for security purpose
ü Prototypes with transparent, flexible and super-hydrophobic photodetectors for smart window applications
ü Novel photodetectors fabricated using inexpensive and scalable solution processed method
ü The photodetectors designed to be visibly transparent
ü Broadband photodetection in UV, Visible and IR regions together
ü The devices are highly stable in air up to few months with hydrophobic protective layer
ü The photodetector demonstrated a remarkably high transparency of 92 %
ü Broadband photodetection starting from 350 nm to 950 nm wavelength of light
ü The photodetector displayed an excellent responsivity of 25 A/W with response time of 0.58 ms
ü The photoresponse performance was unaffected even after 1000 flexing cycles
ü The fabrication process is optimized using simple solution processed method
NDA is done with OSRAM company, Italy
ü Finding industrial collaborator for performing field tests.
Computational identification of prospective molecules for solar-thermal energy storage and hydrogen storage relevant to renewable energy infrastructure. It is expected our endeavour would identify synthetic targets for solar thermal storage and practical systems for hydrogen storage.
ü Solar thermal storage molecules can be cheaper alternative to solar cells that can harvest solar energy by directly storing it and delivering it on demand.
ü Molecular solar-thermal (MOST) storage fuel has emerged as a new approach for storing solar energy for a legitimate period of time (months or years) without any thermal insulation around it. An ideal MOST system must possess some unique characteristics. First and foremost, a MOST candidate must absorb radiation in the UV-visible region (300-700nm) and photoisomerizes to high energy isomer with a high quantum yield. Moreover, the reaction should have a large ground state enthalpy and the kinetic barrier for the thermal back reaction (TBR) should be optimized such that the MOST system stores energy for a reasonable period of time. The conventional MOST systems limited to only three categories: azo-benzene, norbornadiene, and ruthenium based fulvalene systems. However, Photodimerization of anthracene is known for a long time it has not been considered as effective MOST systems due to its poor storage. Using well calibrated theoretical methods we have discovered [n.n](9,10) (n=2-6) anthracenophanes as a new class of potential MOST systems which all unique attributes desired for an ideal MOST system. Our results demonstrate that the gravimetric storage density for longer alkyl-chain linkers are comparable to those for the best-known candidates and making the designed species desirable targets for MOST applications. The storage is mainly based on the strain in the rings formed by the alkyl-chain linkers upon photo-excitation. Our computations bring back focus on hitherto ignored anthracene based systems as potential solar-thermal fuel. We have also investigated if solar thermal storage in anthracene based systems can be enhanced through nanoconfinement within nanotubes.
ü We have also identified B24N24 (a BN fullerene) as a promising candidate for H2 storage through extensive quantum chemical computations and molecular dynamics studies. This is one of the rare molecules which can store over >5% of H2 by weight at room temperature and pressure and can be hydrogenated/dehydrogenated under ambient conditions. Our theoretical studies predict that the hydrogenation of the BN fullerene can be made sustainable exploiting plasmon triggered hydrogenation reaction on Au nanoparticles.
Needed to be identified by the scientist
We anticipate that practical application of the proposed BN hydrogen storage system is likely to be fraught with a major challenge of inexpensive mass production. Though B24N24 fullerene has been synthesized but it is not easily produced like the C60 fullerenes. Hence, synthetics breakthroughs are required for mass production of B24N24.
a. Investigation of the possible intermediates in the O2 reduction cycle by the bio-inspired catalysts using (i) EPR (ii) Raman (iii) Mossbauer spectroscopy and DFT calculations.
b. To enhance H2 production by the bio-inspired catalysts in water containing dissolved O2 by the following approaches:
i. Immobilizing the bio-inspired complexes in micelles/lipid layers on electrodes.
ii. Using antioxidant (like dismutase: Mn complexes) in the electrolytic solution.
iii. Co-absorbing an efficient O2 reducing catalyst with the H2 producing bio-inspired catalyst.
c. Investigation of the mechanism by trapping and characterizing the intermediates during H2 production using (i) Raman (ii) Mossbauer spectroscopy.
d. Electronic structure of the bio-inspired H2 producing catalysts using Raman spectroscopy, Mossbauer spectroscopy and DFT calculations.
e. Enhance the rate of H2 evolution by the Mo catalyst using
i. Layered structure of the catalyst incorporating layers of smaller transition metal ions.
ii. Alternative tetrathiometalate anion.
f. Increase the efficiency of the Co acetate based catalyst by
i. Doping it with similar sized transition metals with lower conductance band
ii. Increase the effective surface area by depositing the catalyst on chemically and electrochemically roughened surfaces.
ü Catalyst development through troubleshooting
ü In-operando mechanistic investigations
ü Hydrogen evolution from naturally abundant water sources.
ü Objectives a and b (part has been achieved). Right now, oxygen tolerant bio-inspired hydrogen evolution catalysts have been developed. These have been tested both with electricity from the grid as well as from PV panels and these systems are very stable.
Needed to be identified by the scientist
ü Key challenges involve enhancing the anodic reaction which is the oxidation of water to make hydrogen. This is currently the bottle neck of the water-splitting technology.
ü The remaining objectives need to be successfully rendered to achieve TRL level 4.
Ferroelectric random access memories (FeRAMs) offer advantages over the currently used flash memories in terms of non-volatility, lower power usage, faster performance, higher read/write endurance (about 1010 to 1014 cycles) and over decades of data retention times. Existing FeRAMs manufactured by companies like Ramtron, Fujitsu, Samsung, Toshiba use toxic lead-based materials (like PZT) and are limited to lower storage densities, higher costs and destructive read processes. Multiferroic (i.e. simultaneous existence of more than one ferroic order parameters) heterostructures comprising of ferroelectric and ferromagnetic materials can overcome the disadvantages of FeRAMs with electrical write and magnetic read operations and offer higher density storage at lower power requirements. Also, multiferroic heterostructures can develop reversible thermal changes in response to more than one species of driving fields (magnetic or electric fields), which is known as multicaloric effects. These reversible thermal changes are analogous to the pressure-induced thermal changes in fluids that are exploited in current refrigeration and air conditioning systems, but they promise much higher energy efficiencies and are environmental friendly since they obviate the need for currently used ozone–depleting refrigerant fluids. The impending energy crisis may be eased by the development of new cooling technologies, based on these multicaloric effects. We propose to develop lead-free and environment friendly materials for the fabrication of multiferroic heterostructures for data storage and cooling applications.
ü Installation of thin film deposition facilities and fabrication of lead-free multiferroic layered thin films for the development of prototype multiferroic heterostuctures in the laboratory setting.
ü Development of testing protocols and facilities for memory and solid state cooling applications.
ü Parallel R&D for the development of the in-house technology and scaling up to the pilot plant level.
ü Multiferroic heterostucture prototype based on sandwiched thin film capacitor geometry with alternate layers of ferroic materials.
ü Demonstration of multiferroic memory operation and performance with 1010 to 1014 read-write cycles and multicaloric cooling performance with high efficiency.
ü Establishment of state-of-the-art thin film fabrication facilities for multiferroic heterostructures using pulsed laser deposition (PLD) and e-beam evaporation techniques for the preliminary research in the laboratory setting and then their translation into industrially viable RF/DC sputtering process.
ü Establishment of test facilities for the measurements of magneto-electric and ferroelectric properties of the prototype devices
ü Successfully installed three state-of-the-art thin film fabrication facilities namely pulsed laser deposition (PLD) (Neocera LLC, USA), UHV-chamber with e-beam deposition (Prevac, Poland) and DC/RF sputter system (Moorfield technology, UK) for growth of thin films and heterostructures.
ü Optimized PLD growth of multiferroic thin film devices of ferroelectric oxides BaTiO3, BaZrTiO3, BaCaZrTiO3 and magnetic oxides of LaSrMnO3 and CoFe2O4 on commercial Si substrates and their characterization using X-ray diffraction and atomic force microscopy.
ü High remanent polarizations (~20 µC/cm2) and magentizations (~ 450emu/cm3) have been recorded in BZCT-LSMO multiferroic heterostructures at room temperature. In the next phase, the memory performance and retention of the devices will be tested.
Academic collaboration with Prof. Sohini Kar-Narayan, Department of Materials Science, University of Cambridge, UK on electrocaloric devices.
ü Discovery of novel multiferroic systems that can exhibit enhanced cross-coupling of ferroic order parameters.
ü Development of cost effective indigenous growth techniques for the multiferroic thin films.
Various contaminants that are found in ground and wastewaters originally occur as minerals in nature, from which contaminant ions are leached either by natural weathering processes or human interventions. Secondary arsenic minerals can be thought of as the most stable mode of contaminant fixation as they are end products of weathering process. The prime objective of this investigation is to look into selected few Arsenic based secondary minerals, and scale the mineralization process in a controllable manner to produce the minerals more efficiently in laboratory for water remediation.
ü Theoretically study the formation pathways and energies of selected Fe(III) and As(III)/As(V) based natural mineral nano-clusters of Ferrihydrite, Tooelite, Scorodite and Pharmacosiderite using Density Functional Theory (DFT).
ü Experimentally study the nanoclusters which form these minerals, and find viable protocols to remove As(III) and As(V) from contaminated water in laboratory scale.
ü Theoretical understanding of mineral formation process from single molecules using 'bottom-up' approach, from respective formation energies using DFT.
ü Laboratory scale synthesis and separation of soluble Ferrihydrite nanoclusters from water.
ü Adsorption of As(III) and As(V) ions onto Ferrihydrite nanoclusters and decontamination of water from Arsenic.
ü Laboratory scale methodology for conversion of the above mentioned pre-nucleation clusters to stable minerals, like Tooelite, Scorodite and Pharmacosiderite.
ü Efficient artificial mineralization route to decontaminate Arsenic(III) polluted water - the Tooeleite Way (DOI: 10.1038/srep26031)
ü Coagulating and flocculating Ferrihydrite clusters: Application of Zinc Acetate
ü Theoretical modelling of Fe(III) oxyhydroxide clusters and formation of Ferrihydrite (DOI: 10.1021/acs.jpca.7b09470)
ü Theoretical Study of Formation of Secondary Arsenic Minerals, Scorodite and Pharmacosiderite (DOI: 10.1021/acsearthspacechem.8b00124)
Needed to be identified by the scientist
ü Inventing processes which could be applicable to very low concentrations i.e. of natural water scale.
ü If successful, making a pilot plant and check project viabilty.
A review in Nature Physics on October, 2017 stated - "The physical description of all materials is rooted in quantum mechanics, which describes how atoms bond and electrons interact at a fundamental level. Although these quantum effects can in many cases be approximated by a classical description at the macroscopic level, in recent years there has been growing interest in material systems where quantum effects remain manifest over a wider range of energy and length scales. Such quantum materials include superconductors, graphene, topological insulators, Weyl semimetals, quantum spin liquids, and spin ices." Therefore, the research in this area is still at a fundamental science level which crucial for developing the next-generation quantum technologies that will meet the urgent technological demands for achieving a sustainable and safe society [Nature Physics, Nov. 2017]. Our group works for developing new and potential Quantum Spin liquid systems and also multiferroic systems and study them.
ü Studying prospective materials with large spin orbit coupling in search of effective quantum spin liquids.
ü Searching unusual magnetic ground states with interesting quantum responses.
ü Studying prospective materials for interesting spintronics application
ü New materials with prospective quantum technological and spintronics application.
ü Developing multiferroic devices with meaningful response.
ü New iridium based compounds are being investigated in search of exciting magnetic ground states such as quantum spin liquids which can have serious implications in the field of quantum computing.
ü High value of spin-orbit coupling is key to several exotic properties for technology and this is directly measured using RIXS.
ü New multiferroic materials are being designed by anion engineering for exciting functionalities such as magnetoelectronics.
ü Several Iridium based oxides have been synthesized and studied in search of exciting magnetic ground states.
ü Symmetry lifting and creation of ferroelectric polarization have been achieved by halide doping in transition metal oxides.
ü Ni-doped CuMnSb systems have been synthesized and probed in order to introduce HMAFM ground state
Needed to be identified by the scientist
ü Discovery of novel multiferroic systems that can exhibit enhanced cross-coupling of ferroic order parameters.
ü Development of exciting magnetic ground states for quantum technological applications.
We have designed a flexible triboelectric nanogenerator (FTENG) using nylon, different nanoparticles or polymer combinations to convert ambient mechanical energy into electrical outputs. An open-circuit output voltage of ~550 V can be easily obtained from the FTENG. The harvested mechanical energy is used for lighting ~100 light emitting diodes and to operate seven segment display enabling prospects for carbon-emission free environment friendly source for powering portable electronic devices. We have shown the capability of using the FTENG as self-powered weight, gait and pressure sensors. The FTENG is simply designed, cost-effective, scalable and high-throughput for possible uses in flexible electronics, self-powered systems and body sensor networks. The same technology has been extended for industrial rubbers for self-powered car.
ü Alternative energy source for power generation using garbage nylon, polymer and nanoparticle combination.
ü Flexible design of the FTENG for self-powered tactile sensing in electronic skin for robotic application.
ü Application in self-powered cars
ü Output voltage of ~550 V can be used for powering remote areas where conventional source of energy is not available.
ü Technology has been patented with Continental, Germany for further research and commercialization in self-powered cars
ü Development of flexible power source with high output voltage for powering remote areas
ü Application in self-powered tactile sensing in electronic skin for robotic application, flexible electronics, self-powered systems and body sensor networks and self-powered cars.
ü Generation of voltages above ~550 V using different material combination for lighting ~100 light emitting diodes and to operate seven segment display enabling prospects for carbon-emission free environment.
ü Development of self-powered weight and pressure sensors.
ü Application in self-powered cars.
Product delivered to Continental, GmbH,Germany
Increasing the output power and durability of the devices, Wireless communication, Commercialization of the products in a large scale
Nanomaterials composed of metal oxides have received enormous attention due to their potential applications in health care and energy related materials. Among them, ZnO and TiO2 are found to be most important oxide nanomaterials for various applications such as in solar energy conversion, sunscreen, antimicrobial agents and photocatalysis for the remediation of environmental pollutants. The generation of ROS is the key factor during the photochemical and photophysical processes between PDT drug and semiconductor nanoparticles.
ü To design hybrid materials of oxide semiconductor-drug for antibacterial and photocatalytic properties
ü Generation of reactive oxygen species with light excitation
ü Understand the ROS activity by using ultrafast spectrscopy
ü The antibacterial efficacy of drug coated ZnO NPs was studied against strains of Gram negative bacteria. This study shows that the therapeutic drug with semiconductor is important for exogenous and endogenous drug-delivery vehicles.
ü The antibacterial efficacy of the nanoconjugate was studied against strains of gram negative bacteria which illustrates that the cells killing are 99.99% and 100% for 20 μl/ml and 21μl/ml nanoconjugate, respectively though, free ZnO NPs and free drug have very little cell killing activity.
ü It is also observed that the nanoconjugate generates sufficient intracellular ROS which is responsible for antibacterial activity and photocatalytic properties. The outcome of the study will provide valuable information for designing new-edge nanoconjugate material having enormous prospective for use in water purification and antibacterial activity. We are trying to design various systems and understand their mechanism.
Unilever Pvt. Ltd.
ü Our investigation on the photo-induced dynamics of ZnO NPs upon complexation with the anticancer drug may open the avenue to utilize the unique electron and proton accepting property of the semiconductor in the development of the photocatalyst as well as drug delivery vehicles.
Semiconductor heterostructures are a class of promising systems that have already found wide scale applications in optoelectronic devices, high electron mobility transistors, solar cells and light emitting diodes. The functionality of such heterostructures can be further controlled at nano-scale. The quantum confinement available in individual nano-particles combined with the fact that the electronic properties of the heterostuctures are actually an unique balance of the properties of the individual parent semiconductors; provides additional functionalization in heterostructures at nano-scale. In fact it has been shown that semiconductor heterostructures at nanoscale offer tunability of the band gap due to band-offset engineering at the interface in a wide range due to the quantum confinement of electrons. Of particular interest, are type-II coupled quantum dots with staggered band alignment where the lowest energy states for electrons and holes are situated in different semiconductors; therefore, at the interface electrons and holes tend to stay spatially apart due to the energy gradient. Thus, type-II alignment is beneficial for application in photovoltaic devices, with excited electrons and holes located at two spatially different parts of the semiconductor, thereby reducing the chances of recombination. Recently we have shown that coupled quantum dots can capture photons and can be integrated as an active component within quantum dot sensitized solar cells.
In addition, such type-II heterostructures also offer the possibility of charge transfer very similar to molecular heterojunctions. Molecular heterojunctions where charge transfer takes place between two molecules behaving as a donor and an acceptor, was earlier proposed to be useful in molecular electronic devices such as in molecular diodes or molecular switching devices. However, their real applications are still limited. Analogously, type II coupled quantum dots, may provide an alternative route to design diode and transistor devices at nanoscale, if the system is asymmetric as a whole, such that occupied and unoccupied states are spatially separated. In particular these systems may exhibit rectification or switching phenomena and may be an alternative to molecular electronics with better performance characteristics.
ü Theoretical investigation of transport characteristics (rectification and switching behavior) of coupled quantum dots.
ü Identify trends and descriptors responsible for their unique transport properties and generate a database.
ü Use the theoretical input for the fabrication prototype diodes and transistors based on coupled quantum dots in the laboratory setting.
ü Parallel R&D for the development of these devices in-house setting and scaling up to the pilot plant level
ü Novel quantum Devices
ü Initiation of calculation framework for transport in coupled quantum dots.
ü Establishment of rectification phenomena in such quantum devices.
ü Establishment of synthesis protocol for such coupled quantum dots.
ü Completed transport calculations on prototype CdS and ZnSe coupled quantum dots.
ü As shown below such coupled quantum dots not only have type II interface but also display rectification characteristics with sizable rectification ratios.
ü Investigated the impact of additional gate voltage on transport characteristics and find it allows to switch the junction between conducting and non-conducting mode effectively realizing an electronic switch.
ü These results are communicated for publication
ü CsS-ZnSe coupled dots with type-II interface has been synthesized and soon transport measurements will be carried out.
1. Scientific Collaboration with Prof. S. Acharya and Dr. B. Das (IACS, Kolkata);
2. Prof. Jens Kortus (University of Freiberg, Germany).
Industrial collaboration yet to be identified by the scientist.
ü Discovery of quantum devices showing rectification and switching at nano-scale.
ü Development of cost effective nano-devices as an alternative to molecular electronics.