skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Two-Color Emitting Colloidal Nanocrystals as Single-Particle Ratiometric Probes of Intracellular pH

Journal Article · · Advanced Functional Materials
 [1];  [1];  [2];  [1];  [1];  [3];  [4];  [5];  [1]
  1. Univ. degli Studi di Milano-Bicocca, Milano (Italy). Dipartimento di Scienza dei Materiali
  2. Istituto Italiano di Tecnologia, Milano (Italy). Center for Nano Science and Technology
  3. Korea Inst. of Science and Technology, Seoul (Korea, Republic of). Photo-Electronic Hybrids Research Center National Agenda Research Division
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  5. Univ. degli Studi di Milano-Bicocca, Milano (Italy). Dipartimento di Scienza dei Materiali; Politecnico di Milano (Italy)

Intracellular pH is a key parameter in many biological mechanisms and cell metabolism and is used to detect and monitor cancer formation and brain or heart diseases. pH‐sensing is typically performed by fluorescence microscopy using pH‐responsive dyes. Accuracy is limited by the need for quantifying the absolute emission intensity in living biological samples. An alternative with a higher sensitivity and precision uses probes with a ratiometric response arising from the different pH‐sensitivity of two emission channels of a single emitter. Current ratiometric probes are complex constructs suffering from instability and cross‐readout due to their broad emission spectra. Here, we overcome such limitations using a single‐particle ratiometric pH probe based on dot‐in‐bulk CdSe/CdS nanocrystals (NCs). These nanostructures feature two fully‐separated narrow emissions with different pH sensitivity arising from radiative recombination of core‐ and shell‐localized excitons. The core emission is nearly independent of the pH, whereas the shell luminescence increases in the 3–11 pH range, resulting in a cross‐readout‐free ratiometric response as strong as 600%. In vitro microscopy demonstrates that the ratiometric response in biologic media resembles the precalibralation curve obtained through far‐field titration experiments. The NCs show good biocompatibility, enabling us to monitor in real‐time the pH in living cells.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1481142
Alternate ID(s):
OSTI ID: 1400821
Report Number(s):
LA-UR-17-31356
Journal Information:
Advanced Functional Materials, Vol. 27, Issue 12; ISSN 1616-301X
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 31 works
Citation information provided by
Web of Science

References (81)

Green and Orange CdTe Quantum Dots as Effective pH-Sensitive Fluorescent Probes for Dual Simultaneous and Independent Detection of Viruses journal October 2007
Regulation of pH in the mammalian central nervous system under normal and pathological conditions: Facts and hypotheses journal May 2008
Experimental Determination of the Extinction Coefficient of CdTe, CdSe, and CdS Nanocrystals journal July 2003
Effect of Core/Shell Interface on Carrier Dynamics and Optical Gain Properties of Dual-Color Emitting CdSe/CdS Nanocrystals journal June 2016
Prospects of Nanoscience with Nanocrystals journal January 2015
Core/Shell Fluorescent Silica Nanoparticles for Chemical Sensing: Towards Single-Particle Laboratories journal June 2006
Polymer microcapsules as mobile local pH-sensors journal January 2007
Dual emission in asymmetric “giant” PbS/CdS/CdS core/shell/shell quantum dots journal January 2016
Photostability of thiol-capped CdTe quantum dots in living cells: the effect of photo-oxidation journal March 2006
Quantum Dot–Fluorescent Protein FRET Probes for Sensing Intracellular pH journal March 2012
The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis journal September 2005
A water-soluble polythiophene–Au nanoparticle composite for pH sensing journal December 2007
Bright White-Light Emission from Semiconductor Nanocrystals: by Chance and by Design journal February 2007
Particle-Based Optical Sensing of Intracellular Ions at the Example of Calcium - What Are the Experimental Pitfalls? journal December 2014
Dual-Color Electroluminescence from Dot-in-Bulk Nanocrystals journal December 2013
Dual Wavelength Electroluminescence from CdSe/CdS Tetrapods journal March 2014
Synthesis and Application of Colloidal CuInS 2 Semiconductor Nanocrystals journal November 2013
Imaging intracellular pH in a reef coral and symbiotic anemone journal August 2009
Intracellular pH regulation in heart journal March 2009
A Fluorophore-Doped Polymer Nanomaterial for Referenced Imaging of pH and Temperature with Sub-Micrometer Resolution journal June 2012
Ultrasensitive, Biocompatible, Self-Calibrating, Multiparametric Temperature Sensors journal October 2015
Spectroscopic and Device Aspects of Nanocrystal Quantum Dots journal September 2016
Stiffness-Dependent In Vitro Uptake and Lysosomal Acidification of Colloidal Particles journal December 2014
Electrochemical Control of Two-Color Emission from Colloidal Dot-in-Bulk Nanocrystals journal June 2014
Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics journal January 2005
Fluorescent probes and nanoparticles for intracellular sensing of pH values journal December 2014
Near Infrared Fluorescence-Based Bacteriophage Particles for Ratiometric pH Imaging journal August 2008
Energy transduction in the F1 motor of ATP synthase journal November 1998
Impact of fixation on in vitro cell culture lines monitored with Raman spectroscopy journal January 2009
Alterations of intracellular pH homeostasis in apoptosis: origins and roles journal June 2004
A quantum dot-based ratiometric pH sensor journal January 2010
Size tuning of MAA capped CdSe and CdSe/CdS quantum dots and their stability in different pH environments journal January 2014
Quantum dot bioconjugates for imaging, labelling and sensing journal June 2005
Fluorescence ratiometric pH sensor prepared from covalently immobilized porphyrin and benzothioxanthene journal August 2005
Coupled and Decoupled Dual Quantum Systems in One Semiconductor Nanocrystal journal August 2005
A hybrid bioorganic interface for neuronal photoactivation journal January 2011
A novel pH “off–on” fluorescent probe for lysosome imaging journal January 2013
Core-shell type dually fluorescent polymer nanoparticles for ratiometric pH-sensing journal September 2008
On the pH-Dependent Quenching of Quantum Dot Photoluminescence by Redox Active Dopamine journal March 2012
The surface science of nanocrystals journal January 2016
A Tunable Ratiometric pH Sensor Based on Carbon Nanodots for the Quantitative Measurement of the Intracellular pH of Whole Cells journal May 2012
Subcellular optochemical nanobiosensors: probes encapsulated by biologically localised embedding (PEBBLEs) journal August 1998
Spectral imaging microscopy demonstrates cytoplasmic pH oscillations in glial cells journal February 2006
A polymer optoelectronic interface restores light sensitivity in blind rat retinas journal March 2013
Use of MTT colorimetric assay to measure cell activation journal November 1986
Dynamic Hole Blockade Yields Two-Color Quantum and Classical Light from Dot-in-Bulk Nanocrystals journal December 2012
Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding journal January 2002
Comparison of three cell fixation methods for high content analysis assays utilizing quantum dots journal October 2008
Ratiometric pH-dot ANSors journal January 2010
pH-Sensitive Capsules as Intracellular Optical Reporters for Monitoring Lysosomal pH Changes Upon Stimulation journal February 2012
Full-Range Intracellular pH Sensing by an Aggregation-Induced Emission-Active Two-Channel Ratiometric Fluorogen journal March 2013
Sensitive and Selective Near-Infrared Fluorescent Off–On Probe and Its Application to Imaging Different Levels of β-Lactamase in Staphylococcus aureus journal May 2014
The effects of basic substances and acidic ionophores on the digestion of exogenous and endogenous proteins in mouse peritoneal macrophages journal March 1986
Dual-color emitting quantum-dot-quantum-well CdSe-ZnS heteronanocrystals hybridized on InGaN∕GaN light emitting diodes for high-quality white light generation journal March 2008
Fluorescent core–shell silica nanoparticles: towards “Lab on a Particle” architectures for nanobiotechnology journal September 2006
Histidine button engineered into cardiac troponin I protects the ischemic and failing heart journal January 2006
Are cancer cells acidic? journal September 1991
Quantum Dot FRET Biosensors that Respond to pH, to Proteolytic or Nucleolytic Cleavage, to DNA Synthesis, or to a Multiplexing Combination journal April 2008
A Ratiometric CdSe/ZnS Nanocrystal pH Sensor journal October 2006
Studies of chemical fixation effects in human cell lines using Raman microspectroscopy journal January 2010
Synthesis of CdSe and CdTe Nanocrystals without Precursor Injection journal October 2005
Quantum-dot/dopamine bioconjugates function as redox coupled assemblies for in vitro and intracellular pH sensing journal August 2010
Formaldehyde fixation. journal August 1985
A Near-Infrared Neutral pH Fluorescent Probe for Monitoring Minor pH Changes: Imaging in Living HepG2 and HL-7702 Cells journal March 2009
Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump journal August 1988
Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays journal December 1983
pH-Sensitive Quantum Dots journal March 2006
pH-Sensitive Photoluminescence of CdSe/ZnSe/ZnS Quantum Dots in Human Ovarian Cancer Cells journal January 2007
Functionalized Metallic Carbon Nanotube Devices for pH Sensing journal February 2007
A Nanogel for Ratiometric Fluorescent Sensing of Intracellular pH Values journal May 2010
Simultaneous Type-I/Type-II Emission from CdSe/CdS/ZnSe Nano-Heterostructures journal December 2013
Localization and Dynamics of Long-Lived Excitations in Colloidal Semiconductor Nanocrystals with Dual Quantum Confinement journal March 2015
One-pot synthesis of fluorescent BSA–Ce/Au nanoclusters as ratiometric pH probes journal January 2014
Design and Synthesis of Heterostructured Quantum Dots with Dual Emission in the Visible and Infrared journal December 2014
Surface Polarization Drives Photoinduced Charge Separation at the P3HT/Water Interface journal August 2016
Sensors and regulators of intracellular pH journal December 2009
Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins journal July 1998
Immunolabeling artifacts and the need for live-cell imaging journal January 2012
A series of naphthalimide derivatives as intra and extracellular pH sensors journal October 2010
Metabolic regulation via intracellular pH journal April 1984
The role of pH dynamics and the Na+/H+ antiporter in the etiopathogenesis and treatment of cancer. Two faces of the same coin—one single nature journal September 2005

Cited By (4)

Highly Stable Core–Shell Structured Semiconducting Polymer Nanoparticles for FRET‐Based Intracellular pH Imaging journal May 2019
Kinetic and spectroscopic responses of pH-sensitive nanoparticles: influence of the silica matrix journal January 2019
Quantum-confined stark effect in the ensemble of phase-pure CdSe/CdS quantum dots journal January 2019
Photocatalytic Activity of Polymer Nanoparticles Modulates Intracellular Calcium Dynamics and Reactive Oxygen Species in HEK-293 Cells journal August 2018