Premium
NMR spectroscopy and MRI investigation of a potential bioartificial liver
Author(s) -
Macdonald Jeffrey M.,
Grillo Mark,
Schmidlin Olga,
Tajiri Dennis T.,
James Thomas L.
Publication year - 1998
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/(sici)1099-1492(199804)11:2<55::aid-nbm502>3.0.co;2-f
Subject(s) - bioartificial liver device , nuclear magnetic resonance , nuclear magnetic resonance spectroscopy , chemistry , biomedical engineering , materials science , medicine , biochemistry , physics , hepatocyte , in vitro
NMR feasibility was established for a coaxial hydrophobic‐membrane bioreactor containing isolated rat hepatocytes with features designed to mimic the human liver. A novel triple‐tuned NMR probe and a perfusion system controlling temperature, gas concentrations, flow‐rate, and pH were used. We determined the optimum coaxial interfiber distance (i.e. diffusion distance) for maintaining hepatocyte viability in two bioreactor prototypes. Prototype no. 1 and no. 2 had diffusion distances of 500 μm and 200 μm, respectively. Cell viability was established by 31 P NMR and trypan blue exclusion. Only prototype no. 2 maintained cell viability for more than 6 h, indicating the importance of diffusion distance. 31 P spectra obtained over this 6 h time period were similar to in vivo spectra of rat liver. The 31 P spectra were found to be more sensitive to subacute cell viability than trypan blue exclusion. In the 1 H and 31 P spectra, 1 H 2 O and inorganic phosphate signals were split in two at all flow‐rates, probably due to bulk magnetic susceptibility effects originating from the three bioreactor compartments. MRI was useful for quality control and determining flow dynamics, fiber integrity, and cell inoculate distribution. MRI revealed that the inner fibers were not centered in either prototype. Although an increased flow‐rate did not influence spectral resolution or chemical shifts, significant degradation of MRI quality occurred above 50 mL/min. NMR spectroscopy and imaging provide valuable, real‐time information on cell biochemistry and flow dynamics which can be used in development and monitoring of bioreactors designed as artificial livers. © 1998 John Wiley & Sons, Ltd.