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Real-Time Monitoring of Cellular Metabolism Using a Bioreactor in a Benchtop NMR Spectrometer

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Abstract

Nuclear magnetic resonance (NMR) is a non-destructive analytical technique that uses non-ionizing radiofrequency (RF) waves for chemical elucidation of living and non-living objects. In this project, we have demonstrated that the metabolism of glucose, fructose, and sucrose in cancer cells and Saccharomyces cerevisae (Baker's yeast) can be monitored in real-time with high chemical specificity using either static or continuous-flow bioreactor tubes inside a benchtop NMR spectrometer. Both proton (1H) and carbon-13 NMR spectroscopic measurements were performed which allowed us to track the biochemical fates of a variety of nutrients in cells. Experimental results will be discussed in light of the importance of real-time biochemical detection in living cells, as well as possible expansion to a variety of cell lines and biochemical quantitation of their enzymatic reactions. This study is supported by the Welch Foundation grant AT-1877-20180324, DOD grants W18XWH-17-1-0303 and W81XWH-19-1-0741, Cancer Prevention and Research Institute of Texas (CPRIT) grant RP180716, and the UTD Collaborative Biomedical Research Award (CoBRA).

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Authors

  • James Mulhern

    Department of Physics, University of Texas at Dallas, Richardson, TX 75080

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory