Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

A scalable and autoclavable oxygen nanosensor platform for metabolic monitoring of Saccharomyces cerevisiae in a bioreactor and other in situ systems

Journal Article · · Mikrochimica Acta
 [1];  [1];  [2];  [2];  [1];  [1];  [2];  [1]
  1. Colorado School of Mines, Golden, CO (United States)
  2. Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Polymer-encapsulated dye nanoparticle sensors are a valuable approach to achieving in situ analyte measurements with luminescence; however, typical emulsion-based nanosensors are poorly suited for large-scale biological samples due to limitations of synthesis scalability and stability. Branched polyethylenimine (PEI) is a versatile polymer scaffold ideal for constructing nanoparticles with various covalently conjugated moieties due to their high density of reactive primary amines, high water solubility, and biological stability. In this work, we used branched polyethylenimine as a scaffold-based approach for making a stable and scalable ratiometric oxygen sensor. Pt (II) tetracarboxyporphine was used as an oxygen-sensing dye and coumarin 343 as a reference dye, all covalently linked to the PEI scaffold producing a product that could withstand sterilization procedures and easily be scaled. To minimize toxicity from the PEI scaffold, we conjugated it with 2000 MW PEG. The applicability of the sensors was demonstrated in a 200 mL Saccharomyces cerevisiae yeast culture, using orthogonal luminescent and electrochemical oxygen measurements to validate sensor response and measure the metabolic activity of the yeast in our culture. Further, this approach was able to match the sensitivity of our electrochemical measurements while improving upon drawbacks of other luminescent methods of oxygen detection, demonstrating effective monitoring for at least 20 h. Our scaffold-based approach is a modular and easily translatable technology that could be useful in various biotechnological applications.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
2566014
Report Number(s):
LLNL--JRNL-2005003
Journal Information:
Mikrochimica Acta, Journal Name: Mikrochimica Acta Journal Issue: 2 Vol. 192; ISSN 0026-3672
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

References (35)

Tracking Cancer Metastasis In Vivo by Using an Iridium-Based Hypoxia-Activated Optical Oxygen Nanosensor journal June 2015
Luminescent sensing and imaging of oxygen: Fierce competition to the Clark electrode journal June 2015
Long‐term continuous monitoring of dissolved oxygen in cell culture medium for perfused bioreactors using optical oxygen sensors journal March 2004
An adaptive state estimator for detecting contaminants in bioreactors journal August 1989
On the Design of Fluorescent Ratiometric Nanosensors journal July 2010
Effects of light intensity, oxygen concentration, and carbon dioxide concentration on photosynthesis in algae journal March 1975
Quadruply-labeled serum albumin as a biodegradable nanosensor for simultaneous fluorescence imaging of intracellular pH values, oxygen and temperature journal July 2019
Algae: the world’s most important “plants”—an introduction journal September 2010
Indicators for optical oxygen sensors journal November 2012
Oxygen uptake rate in microbial processes: An overview journal May 2010
Phosphorescence based O 2 sensors – Essential tools for monitoring cell and tissue oxygenation and its impact on metabolism journal December 2016
Polyethylenimine (PEI) in gene therapy: Current status and clinical applications journal October 2023
A review of chemosensors and biosensors for monitoring biofilm dynamics journal November 2021
Staying alive! Sensors used for monitoring cell health in bioreactors journal January 2018
Fundamentals of Emulsion Polymerization journal June 2020
Polyethylenimine-Assisted Generation of Optical Nanoprobes for Biosensing Applications journal June 2020
Quantum Dots in an Amphiphilic Polyethyleneimine Derivative Platform for Cellular Labeling, Targeting, Gene Delivery, and Ratiometric Oxygen Sensing journal May 2015
Sensors in a Flash! Oxygen Nanosensors for Microbial Metabolic Monitoring Synthesized by Flash Nanoprecipitation journal September 2022
Triplet–Triplet Annihilation Upconversion-Based Oxygen Sensors to Overcome the Limitation of Autofluorescence journal August 2023
Persistent Luminescence Nanosensors: A Generalized Optode-Based Platform for Autofluorescence-Free Sensing in Biological Systems journal June 2024
Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems journal May 2009
Quenching of fluorescence by oxygen. Probe for structural fluctuations in macromolecules journal October 1973
Amperometric Gas Sensors - A Review journal February 2008
Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals journal March 2015
A near-infrared optical nanosensor for measuring aerobic respiration in microbial systems journal January 2022
Branched and linear poly(ethylene imine)-based conjugates: synthetic modification, characterization, and application journal January 2012
Biological detection by optical oxygen sensing journal January 2013
Optical 4D oxygen mapping of microperfused tissue models with tunable in vivo-like 3D oxygen microenvironments journal January 2022
Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody journal March 2014
A Water‐Soluble Luminescence Oxygen Sensor journal February 1998
Engineered algae: A novel oxygen-generating system for effective treatment of hypoxic cancer journal May 2020
Luminescent Nanosensors for Ratiometric Monitoring of Three-Dimensional Oxygen Gradients in Laboratory and Clinical Pseudomonas aeruginosa Biofilms journal October 2019
Editors’ Choice—Luminescent Oxygen Sensors: Valuable Tools for Spatiotemporal Exploration of Metabolism in In Vitro Systems journal July 2023
Effectiveness and potential environmental impact of a yeast-based deoxygenation process for treating ship ballast waters journal February 2013
Oxygen dynamics at the base of a biofilm studied with planar optodes journal January 1998