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Innovative new quantum-dot imaging probes cut through noise, leading to more effective disease diagnoses

Susan McKenna
2/7/2020 9:09:00 AM

In a study conducted at the University of Illinois at Urbana-Champaign, a research team developed a new form of quantum dots with short-wave infrared (SWIR) emission for imaging single molecules in cells and tissues. The SWIR is a unique spectral range which the eye cannot see, and the quantum dots’ emission can be tuned over an extremely broad range of colors and spectrums, from the visible to the infrared, allowing for a wide range of use.

“We call this spectral range VIR, and call the quantum dots VIR-QDs,” said Andrew Smith, associate professor of Bioengineering and principal investigator on the study. “This allows us to perform quantitative comparisons of different spectral ranges. In addition, these are the first SWIR-QDs suitable for microscopic imaging of tissues – they are compact to allow access to the cell cytoplasm, bright enough to see and count individual molecules, and stable enough to withstand the environments within complex biological samples.”

The big advantage of the SWIR is that there is almost no autofluorescence (background signal) emitted from cells compared with the most commonly used spectral ranges in the visible light. This allows the researchers to see sharper details in images and recognize individual molecules more accurately. The team evaluated a wide range of biological studies — from cells to tissues — replacing visible wavelength QDs with SWIR-QDs, finding that all scenarios benefitted from their use.

In this schematic provided by the authors, the left panel shows the structure of a quantum dot, which can be attached to peptides like EGF, to DNA, and to IgG antibodies, allowing labeling of specific molecules in cells and tissues. The right panel depicts optical spectra of 5 different VIR-QDs, showing the wavelengths and energies of light absorption (solid lines) and light emission (filled curves). VIR-QD emission can span the visible spectrum, near-infrared-I spectrum, and short-wave infrared spectrum.
In this schematic provided by the authors, the left panel shows the structure of a quantum dot, which can be attached to peptides like EGF, to DNA, and to IgG antibodies, allowing labeling of specific molecules in cells and tissues. The right panel depicts optical spectra of 5 different VIR-QDs, showing the wavelengths and energies of light absorption (solid lines) and light emission (filled curves). VIR-QD emission can span the visible spectrum, near-infrared-I spectrum, and short-wave infrared spectrum.

Quantum dots are important to life sciences research in many ways. They help us better understand biology, are used to develop new drug therapies and medical technologies, and are used for detecting diseases such as cancer in patients. The SWIR quantum dot research conducted by Smith and his team is unique because, for the first time, it shifts the emitted light colors from the visible spectrum into the short-wave infrared spectrum, opening the door to much more effective imaging.

“In the visible spectrum, signals that we are trying to detect are superimposed on top of a large amount of useless noise that emanates from cells and tissues, obstructing signals from our probes,” Smith said. “In the SWIR, the noise is almost entirely absent, allowing us to see our probe signals unimpeded. This allows us to collect higher-resolution images at a faster rate and more accurately detect proteins and RNA. We, therefore, can detect very low concentrations of molecules that are essentially invisible using normal procedures and can even see individual molecules within cells.”

The researchers expect the biggest impact of this work to be in diagnosing diseases in patients. For example, in a clinical diagnosis of cancer, tissue is extracted from the patient and examined through a microscope for evidence of a tumor. The tumor tissue often is stained with molecular probes, Smith says, “but the outcomes are often subjective. SWIR-QDs can be used to gain exquisite precision in measured outcomes for these tissues because there are no interfering signals, which could result in more accurate classifications of tissue diseases for patients.” This means a significant increase in precision in the therapies prescribed to treat the diseases.

Also of interest is the broader understanding of human tissues that this work promises. The ongoing Human Cell Atlas and NIH HubMap projects aim to generate a sophisticated, comprehensive map that is the cell-level equivalent of the human genome project for human DNA. SWIR-QDs could contribute to that body of knowledge in that they provide a new, higher-precision label for classification and imaging of cells, and this contribution is part of what Smith’s lab is working on.

In their next steps with this work, Smith says the researchers are applying the materials for tissue mapping, and they are developing lower-cost instrumentation so that the probes can be broadly adopted.

“Many labs do not have cameras that can see these SWIR-QDs yet,” Smith said. “Some of these cameras are low in cost, but instruments need to be developed that can make full use of their capabilities.”

The team, which includes Paul Selvin, professor of Physics and of Biophysics at Illinois, and Phuong Le and Mohammad U. Zahid, both recent Ph.D. graduates in Bioengineering at Illinois, published their work in the Journal of the American Chemical Society in the January 22, 2020, issue. Selvin and his lab team played an important role in this project, particularly through instrument design and for imaging and testing of the new quantum dot materials.

This work was supported by the National Institute of Neurological Disorders and Stroke and the National Institute of General Medical Sciences of the National Institutes of Health, and by the National Science Foundation.

The study, “Short-Wave Infrared Quantum Dots with Compact Sizes as Molecular Probes for Fluorescence Microscopy,” is online at: pubs.acs.org/doi/10.1021/jacs.9b11567 .

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