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Medical Science

Argonne maintains a wide-ranging science and technology portfolio that seeks to address complex challenges in interdisciplinary and innovative ways. Below is a list of all articles, highlights, profiles, projects, and organizations related specifically to medical science.

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  • 2D layer property images, automated processing.
    Intellectual Property Available to License

    US Patent 7,538,938; US Patent 9,816,952 B2; US Patent 8,465,200; US Patent 7,365,330
    • Thermal Multi-layer Coating Analysis (IN-05-125), (IN-14-032)
    Illustration of pulsed thermal imaging of a 4-layer material system (L = Layer).

    The Invention 

    Pulsed thermal imaging is widely used for nondestructive evaluation of advanced materials and components. Thermal imaging methods to analyze single-layer materials are well developed. However, a general method for analyzing multi-layer materials and coatings/films has not been developed due to the complexity of material systems and lack of an analytical solution. This technology provides a general method, test system including a filter, and numerical algorithm for automated analysis of thermal imaging data for multi-layer coating materials. 

    Argonne’s pulsed thermal imaging-multilayer analysis method can accurately measure coating thermal conductivity and heat capacity (and/or thickness) distributions over an entire component’s surface. The method analyzes a temporal series of measured thermal imaging data to determine the properties for all coating layers based on a multilayer model. Argonne’s invention is currently the only method that can analyze coatings of more than one layer, is fully automated to produce 2D layer property images, and has validated high accuracy.

    Argonne’s approach includes an infrared filter for flash lamps to eliminate the flash’s infrared radiation, ensuring accurate detection of surface temperature during pulsed thermal imaging tests. 

    Key to Argonne’s thermal multi-layer analysis method is the numerical algorithm used for automated analysis of thermal imaging data for multi-layer materials, implemented in dedicated, Argonne-created software that allows for complete data-processing automation without the need of user intervention.

    Photograph (left) and thickness image (right) of a thermal barrier coating specimen with four sections of thicknesses.

    Benefits 

    • Allows fast 2D imaging of multi-layer material properties of an object from one surface 
    • All-in-one solution that includes method, optical filter, and analytical software for thermal multi-layer material analysis 
    • Imaging is nondestructive and fast 
    • Eliminates infrared radiation to assure data accuracy 
    • Automated analysis of imaging data 

    Applications and Industries 

    • Multi-layer coating materials development 
    • Manufacturing quality control 
    • Coating degradation monitoring 
    • Medical applications 

    Developmental Stage 

    Proof of Concept: the technology has been tested and proven to work for coated engine parts. 

    Argonne Inventions 

    • IN-05-125, Optical Filter for Flash Lamps in Pulsed Thermal Imaging View the patent.
    • IN-14-032, Method and Apparatus for Material Thermal Property Measurement by Flash Thermal Imaging View the patent.
    • IN-06-017, Method for Thermal Tomography of Thermal Effusivity from Pulsed Thermal Imaging View the patent
  • Bringing flexibility and assurance to containment systems
    Intellectual Property Available to License
    US Patent 9,757,866
    • Containment Unidirectional Resource Loading System (ANL-IN-12-052)

    The Invention 

    Gloveboxes are used in research, product development, process development, scale-up, testing and production labs across the world. They allow safe handling of materials such as nano powders, noxious chemicals, flammable vapors, radioactive materials, DNA/RNA snippets, battery materials and more. Gloveboxes are used to guarantee worker safety, experimental integrity and assure that testing batches are not contaminated. However, most gloveboxes today are task-specific and can only be used for one kind of scientific protocol; in addition, often material must be transported in or out of the glovebox without loss of containment. To meet these challenges, Argonne invented CURLS for gloveboxes, with the flexibility to apply to any containment system. 

    CURLS prototype tunnel port and cartridge

    CURLS is a tunnel” that installs in an existing glove port along with various co-designed resource cartridges that allow easy and rapid change-over of resources without losing containment. With CURLS, when a different resource is required, the user merely inserts the specific resource cartridge into the CURLS tunnel until it engages, causing the used resource cartridge to drop into the glovebox — all while maintaining complete containment. 

    The novel CURLS continuous sleeve ring revolutionizes material transfer in and out of gloveboxes. All CURLS resource cartridges are designed to break into several pieces so that used cartridges can be easily removed from the glovebox via bag-out” so that used cartridges do not clutter the work space.

    Benefits 

    • No breach of containment or batch contamination 
    • Quick change-over of resources 
    • Allows gloveboxes to be multi-tasking” and reconfigured on the fly” 
    • Fewer lost experiments and production batches 
    • Simplifies containment procedures 

    Applications and Industries 

    • Nuclear industry 
    • Material science, chemistry and physics laboratories 
    • Pharmaceutical industry 
    • Biotech industry 
    • Semiconductor and battery industries 
    • Any industry where containment systems are used
    Schematic of CURLS bag in” (taken from patent application)

    Developmental Stage 

    Prototyping – demonstration unit already used to process 38 drums of plutonium powder-laced materials 

  • A unique system for membrane protein expression makes it possible to obtain reasonable yields of functional membrane protein
    Intellectual Property Available to License
    US Patent 6,465,216; US Patent 8,455,231; US Patent Application 2014/0080176
    • A System for Expression of Membrane Proteins (ANL-IN-06-099)

    The Innovation

    Cell membranes are the interface between an organism and its environment. These biological structures contain proteins that are extremely important for many cellular processes (e.g., nutrient uptake, metabolic waste excretion, energy metabolism, and response to external stimuli). Because of their mediating roles between external stimuli and internal cellular metabolism, membrane proteins account for more than 60% of drug targets.

    Schematic of the overall approach that excels in the overproduction of membrane proteins

    Membrane proteins, however, present unique challenges because they are hydrophobic, which means they are highly unstable and insoluble in the aqueous environments typically used to produce and characterize hydrophilic proteins. It is therefore difficult to produce and purify them in quantities and at a level of quality sufficient for conducting structural or functional studies. That is also why the number of unique membrane protein structures determined to date lags far behind the number of those known for water-soluble proteins.

    There are few available systems that enable heterologous expression of membrane proteins. Most were adapted from soluble protein expression systems and usually present challenges for research projects working on membrane proteins. For example, such systems using E. coli often produce insoluble aggregates or cause host toxicity as membrane space is limited. Alternatively, eukaryotic expression systems are costly and cumbersome to implement.

    In contrast, a unique system for membrane protein expression invented by Philip Laible and Deborah Hanson in the Biosciences Division at Argonne National Laboratory makes it possible to obtain reasonable yields of functional membrane protein. This proprietary method uses photosynthetic bacteria (Rhodobacter) for the expression of heterologous membrane proteins.

    Rhodobacter cells produce extremely large amounts of intracellular membrane when cultured under certain conditions.Synthesis of foreign (or native) membrane proteins and this intracellular membrane can be coordinated in these bacteria. Partial purification of the expressed membrane proteins is afforded because they are sequestered in these membrane vesicles, which are easily separated by size. Vesicles enriched in target membrane proteins can be used directly in many types of activity assays. Recently, work with the Rhodobacter expression system has become less cumbersome by additional engineering of strains that allow the direct uptake of foreign DNA (patent application pending). Previous methods used a two-step process: foreign DNA was first introduced into E. coli cells, which were then mated with Rhodobacter cells – mobilizing and transferring the foreign DNA by a process known as conjugation. Rhodobacter strains can now be manipulated using common laboratory methods (e.g., chemical or electroporetic transformation).

    The Benefits

    This method offers such advantages as lower production costs, ease of purification, scalability, and high yields of membrane proteins (0.5 mg/L to as high as 20 mg/L culture). The system permits the simultaneous production and sequestration of foreign membrane proteins, yielding a higher fraction of proteins in soluble form, as well as avoiding toxicity to the host. It has strong applications in both the pharmaceutical and biotechnology industries. As biologics become more mainstream, large quantities of active membrane proteins will be required for regulatory testing. Certain membrane proteins of therapeutic importance have been overexpressed with success, and research is under way to validate the method further for other classes of industrially relevant membrane proteins.

    Application and Industries

    • A research tool for expression of challenging proteins
    • Scaled production for biologics testing and drug discovery efforts

    Publication Information

    P. D. Laible et al., J. Struct. Funct. Genomics 5: 167–172 (2004)

    Developmental Stage

    Ready for commercialization

  • A process for amorphous pharmaceuticals
    Intellectual Property Available to License
    US Patent 9,327,264 B2
    • Containerless synthesis of amorphous and nanophase organic materials

    The Invention 

    (a) Acoustic levitator levitating several samples simultaneously (shown as white spheres) with a 14mm spacing. Illustrations on

    Making fast-acting pharmaceuticals is a goal of almost every drug company. The route of delivering pharmaceuticals in the form of amorphous solids has long been recognized as a possible way to improve dissolution rates and to increase both solubility and bioavailability. Development in this direction is becoming increasingly important due to the emergence of many new drugs that are virtually insoluble in their crystalline form. Researchers at Argonne National Laboratory have developed the technique of acoustic levitation to prepare amorphous solids and molecular gels that can be easily applied to the pharmaceutical manufacturing process. This technique would improve the solubility and bioavailability of several drugs. 

    The acoustic levitation techniques developed at Argonne keeps the drug solution from making contact with any surface whatsoever during the solvent evaporation process. This containerless process was developed and tested on several over-the-counter and prescription pharmaceuticals. Several of the pharmaceuticals amorphized using the Argonne process remained completely amorphous for four months or longer. Please review the publication for additional details.

    Benefits 

    A containerless process: 

    • Precludes the possibility of a drug’s interaction with its container; 
    • Provides a more effective means of synthesizing amorphous pharmaceutical compounds; 
    • Offers higher yields than current state-of-the-art methods; 
    • Reduces the potential for contamination during the manufacturing process; and 
    • Is expected to advance the development of amorphous drug forms, increasingly important due to new drugs that are virtually insoluble in crystalline form.

    Applications and Industries 

    Pharmaceutical industry 

    Developmental Stage 

    Proof of principle 

  • Thermal tomography is used to create three-dimensional images of skin damage due to radiation treatment
    Intellectual Property Available to License

    US Patent 7,365,330; US Patent 7,538,938
    • Three-Dimensional Thermal Tomography (3DTT) Advances Cancer Treatment (ANL-IN-06-017)

    The method allows more rapid, yet still non-invasive, detection and is expected to enhance the treatment experience for breast cancer patients. 

    Background and Need 

    Change in temperature over time (left) is used to calculate the 3-dimensional effusivity distribution (right). Each slice repres

    Because cancer cells grow more quickly than healthy cells, they are typically a few degrees higher in temperature. This attribute makes it possible to use thermal imaging to detect them. For this reason, passive thermal imaging is helpful in detecting breast cancer. In active thermal imaging, heat or cold is applied to an object and an infrared camera is used to observe the resulting temperature change. 

    Thermal imaging can be used to analyze even multilayered materials— making the methodology even more useful than conventional processes like X-rays, CT and ultrasonic scanning for such applications. 

    The Invention 

    A team of researchers from Rush University Medical Center and Argonne National Laboratory is using a 3-D technique to detect early skin changes due to radiation treatment in breast cancer patients. Use of the technique could facilitate earlier delivery of treatment to prevent radiation skin damage in these patients. They can develop a skin reaction that, in severe cases, causes discomfort and can disrupt therapy. However, if detected early, skin reactions are preventable or treatable. 

    Clinical tests used 3DTT to measure the skin’s thermal effusivity—a tissue property that quantifies its ability to exchange heat with its surroundings. In the test, a flash of filtered light heats the skin while an infrared camera captures a time series of images that display skin temperatures by color. Using an algorithm to calculate temperature changes and determine the thermal effusivity at different skin depths, the researchers discovered the effusivity values of damaged skin tissue differ from that of healthy skin. 

    Preliminary data show that marked reductions in the effusivity levels of irradiated skin occur well in advance of development of high-grade skin reactions. Soon, the team hopes to apply the 3DTT technique in breast cancer patients. Also underway is the development of an even more sophisticated algorithm to improve resolution at subsurface depths.

    Benefits 

    Three-dimensional thermal tomography offers significant benefits over existing technologies: 

    • Is non-invasive and enhances healing. 
    • Measures tissue property changes without interrupting treatment. 
    • Provides rapid feedback to clinicians during diagnosis and treatment. 
    • Detects other conditions, such as skin cancer, where changes in effusivity would enable researchers to locate and quantify the number of cancer cells. 
    • Measures skin damage caused by electricity or lightning and to evaluate the progress of skin grafts. 
    • Applicable to virtually any material up to about 10 millimeters deep. 
    • Enables clinicians to image multilayered materials without knowing the number of layers in advance, unlike other imaging technologies. 
    • Offers higher spatial resolution compared to that of other technologies such as X-rays, CT, and ultrasound. 

    Applications and Industries 

    The 3DTT technique has wide application in medicine as well as in other industries where in situ inspection is required, such as the imaging of engine components or the space-shuttle thermal protection system. 

    Developmental Stage 

    This technology is ready for prototype development.

  • Improved treatment of X-ray resistant and inoperable cancers and tumors
    Intellectual Property Available to License
    US Patent 7,312,461
    • Endoscopic Electron Beam Cancer Therapy (ANL-IN-04-067)
    This figure shows a comparison of X-ray radiation treatment and electron beam treatment. At left, a false color map displays ene

    Manipulating electron beam cancer therapy so it can be used treat internal cancers and tumors has the potential to revolutionize oncology. This ground-breaking innovation can provide a successful and cost-effective means of treating cancer in previously inoperable or radiation-sensitive areas of the body. 

    Technology Description 

    By delivering large irradiation doses in a short time, electron beams have proven to be very effective in cancer treatment. But the electron is also strongly absorbed by tissue, limiting this treatment to surface cancers and procedures that require large surgical incisions to expose the body core. 

    Researchers at Argonne National Laboratory, led by John Noonan, have discovered a way to turn the negative attributes of electron beam cancer therapy into advantages. If the electron beam can be transported to the internal cancer without exposure to tissue, the beam can be absorbed by the tumor only. With this approach, healthy tissue is not exposed to radiation. 

    An electron source has been designed to have very low beam emittance. The beam is sub-millimeter in diameter and stays small over meters of transport in free space. It will allow for an articulated, hard-walled laparoscopic tube to be inserted through a small incision and positioned directly at the tumor. The beam can vary energy from 1 million electron volts (MeV) to 10 MeV, permitting it to cover a tumor size of about 0.5 cm to 5 cm, respectively. 

    Initially, electron beam treatment can be used on X-ray radiation resistant tumors. The electrons destroy cancerous cells by direct damage to the DNA, and not by electron displacement in molecules as with X-rays. Ultimately, the electron beam therapy would be a competitor to all X-ray treatments. 

    Potential Benefits 

    The damage volume of the electron irradiation can be controlled very closely by changing the electron beam energy. This precise exposure provides several new cancer therapies or treatments in previously inoperable or radiation-sensitive locations, such as the spine, nerves, optic nerve, and organs. Electron beam treatment of brain tumors is another new opportunity. In this case, the laparoscopic tube provides an advantage. After the irradiation, the tube can be used to evacuate the mass of dead tissue, which can become destructive to healthy brain cells. 

    Enormous doses can be delivered to the tumor without worrying about total body dose exposures, as is required for X-rays. The electron beam can be tailored to irradiate a very precise volume, so an oncologist can direct the irradiation at the tumor and whatever adjacent tissue they feel necessary. Another major advantage over X-rays is the amount of treatment time required. X-ray treatments can go on for months, while electron beams may potentially only require one session, providing a significant improvement in patient care. 

    The electron beam system is compact so it could fit in an operating room—probably even under the operating table. Except for the electron source, the system uses conventional accelerator technology. The production cost of the unit should be much less than that of existing radiation therapy systems. 

    Development Stage

    Prototype

    Scientific Publication

    Noonan J., and Lewellen J.W., 2005, Field-emission cathode gating for RF electron guns,” Physical Review, Special Topics - Accelerators and Beams 8: 033502. 

  • Narayanan Kasthuri

    Dr. Kasthuri is a neuroscience researcher at Argonne and an assistant professor (adjunct) in the Department of Neurobiology at The University of Chicago.
  • Midwest Center for Structural Genomics

    The primary objective of the MCSG is to rapidly determine the structures of strategically selected and biomedically important targets, including proteins from pathogens and higher eukaryotes.