Towards CMOS Nuclear Magnetic Resonance Spectroscopy: Design, Implementation and Experimental Results

Nuclear Magnetic Resonance (NMR) Spectroscopy is used intensively along with other ancillary spectroscopic and characterization techniques. The design and implementation of High Throughput NMR Spectroscopy is a key challenge to accelerate the drug discovery process. On the other hand, the current conventional NMR technologies are expensive and bulky. The development of novel handheld NMR spectroscopy is a key challenge towards NMR spectroscopy for Point-of-Care (PoC) diagnostics applications. This thesis addresses the above-mentioned challenges of High Throughput NMR Spectroscopy and Handheld NMR spectroscopy by developing new integrated circuits dedicated to NMR spectroscopy using Complementary Metal Oxide Semiconductor (CMOS) technology. Simulation and characterization results were also used to prove the functionality and applicability of the proposed techniques. We have designed two CMOS chips using 0.13-m technology, first chip includes number of new vertical microcoils and LNA with 780 pV/Hz at 300 MHz and the second one is a new dual-path NMR receiver

High Relevance Combined with High Resolution: Advantages of in vivo Two-Photon Microscopy for Drug Discovery

Despite breath-taking technological progress, modern pharmaceutical industry suffers from high attrition rates. In fact, only one in twenty lead compounds identified in non-clinical development passes through clinical trials and to market. The unacceptably low predictive power of many preclinical models stems, in part, from the lack of relevance and/or poor resolution of imaging techniques employed in drug development. Thus, in vivo imaging typically does not yield sufficient spatial resolution, whereas in vitro microscopy methods lack pathophysiological relevance. At present, only the in vivo two-photon microscopy (IV2PM) combines the crucial advantages of both imaging and microscopy, as it introduces the nanometer-scale spatial resolution of in vitro microscopy into the highly relevant context of in vivo imaging. In the present concise review, we discuss the most exciting applications of this game-changing technique in academic research of the past decade, and provide an outlook on the future role of IV2PM in drug discovery and development.Non peer reviewe

Recent developments and application of metabolomics in cancer diseases

      Metabolomics studies provide useful information about health and disease status. Metabolite based investigations on various cancers is a powerful approach to diagnosis, prognosis and therapy of cancer diseases. Recently by using advanced analytical techniques such as NMR and MS and its hyphenation methods, global metabolic profiling of diseases has been possible. It is predictable that international contributions and software developments in the future will lead to accurate instrumental analysis based on  a large number of  human samples that finally will improve validation methods and reach this field from the research phase to the clinical phase. In this review, we also discussed the latest developments in analytical methods, application of data analysis, investigation of useful databases and the curent application of metabolomics in cancer diseases that have led to the identification of related biomarkers. In continuation, we listed biomarkers involved in cancer diseases that have been published during recent years.

Focal Spot, Winter 2006/2007

https://digitalcommons.wustl.edu/focal_spot_archives/1104/thumbnail.jp

What NMR can do in the biopharmaceutical industry

LBK

2011 Strategic roadmap for Australian research infrastructure

The 2011 Roadmap articulates the priority research infrastructure areas of a national scale (capability areas) to further develop Australia’s research capacity and improve innovation and research outcomes over the next five to ten years. The capability areas have been identified through considered analysis of input provided by stakeholders, in conjunction with specialist advice from Expert Working Groups   It is intended the Strategic Framework will provide a high-level policy framework, which will include principles to guide the development of policy advice and the design of programs related to the funding of research infrastructure by the Australian Government. Roadmapping has been identified in the Strategic Framework Discussion Paper as the most appropriate prioritisation mechanism for national, collaborative research infrastructure. The strategic identification of Capability areas through a consultative roadmapping process was also validated in the report of the 2010 NCRIS Evaluation. The 2011 Roadmap is primarily concerned with medium to large-scale research infrastructure. However, any landmark infrastructure (typically involving an investment in excess of $100 million over five years from the Australian Government) requirements identified in this process will be noted. NRIC has also developed a ‘Process to identify and prioritise Australian Government landmark research infrastructure investments’ which is currently under consideration by the government as part of broader deliberations relating to research infrastructure. NRIC will have strategic oversight of the development of the 2011 Roadmap as part of its overall policy view of research infrastructure

To metabolomics and beyond: a technological portfolio to investigate cancer metabolism

Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression, metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic and redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field has seen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell or a tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinical applications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the field enabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, the upgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellular resolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent of functional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and novel therapeutic targets that in concert with other technologies allow patient stratification and identification of new treatment regimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emerging technologies, emphasizing advantages, disadvantages and applications with the potential of leading the development of innovative anti-cancer therapies

Metabolomics and its application for non-invasive embryo assessment in IVF

Morphology and cleavage rate remain the mainstay of embryo assessment. However, a number of additional technologies for this application are under investigation. These include the measurement of glucose, lactate, pyruvate or amino acid levels in the embryo culture media, assessment of oxygen consumption by the embryo, genomic and proteomic profiling, and most recently, analytical examination of the embryonic metabolome. As the number of assisted reproduction cycles increases worldwide, improvements in the ability to quickly and non-invasively identify the best embryos for transfer remain a critical goal for reproductive medicine. Recent studies suggest that metabolomic profiling of embryo culture media using optical and non-optical spectroscopies may provide a useful adjunct to the current embryo assessment strategies and provide insight into the phenotype of embryos with increasing reproductive potential

Novel Application Of Untargeted Metabolomics To Diseases Of Neurosurgical Significance

Metabolomics, an emerging technique to study hundreds of small-molecule metabolites simultaneously, has been seldom applied to diseases of neurosurgical significance. We utilized metabolomics to explore two distinct questions: 1. to identify global metabolic changes and metabolite predictors of long-term outcome in aneurysmal subarachnoid hemorrhage (SAH) patients, 2. to identify differential metabolites profiles of radiation necrosis vs. recurrent tumor of metastatic brain lesions post-Gamma Knife radiosurgery. The first study applied gas chromatography time-of-flight mass spectrometry (GC-TOF) to cerebrospinal fluid samples collected from 15 high-grade aSAH patients (modified Fisher grades 3 and 4). Analysis was performed at two time points; metabolite levels at each time point were correlated with Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Of 97 metabolites identified, 16 metabolites (primarily free amino acids) significantly changed between the two time points; these changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH. These results suggest that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcomes. This is the first study to implicate 2- hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis. The second study applied GC- TOF to histologically-validated specimens (7 each) of pure radiation necrosis and pure recurrent tumor obtained from patient brain biopsies. Of 141 metabolites identified, 17 were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 metabolites were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. This is the first tissue- based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop non-invasive metabolic imaging techniques