The Unseen Revealed

How Sandia's Bio-Innovations Are Revolutionizing Health and Security

Hyperspectral Imaging Biothreat Detection LDRD Research

The Art of Seeing Differently

What if our eyes could see the invisible? Not just the hidden dimensions of microscopic worlds, but the subtle biochemical conversations that determine health versus disease, safety versus danger?

At Sandia National Laboratories, scientists are doing exactly that—developing revolutionary technologies that reveal what was previously undetectable. Through cutting-edge research funded by the Laboratory Directed Research & Development (LDRD) program, these innovators are transforming how we identify biological threats, diagnose diseases, and understand complex biological systems 1 2 .

This article explores how Sandia's unique approach to science is generating powerful new tools that see the unseen and protect the nation's health and security in previously unimaginable ways.

The LDRD Program: Sandia's Engine for Innovation

High-Risk, High-Reward

Sandia's LDRD program represents the lifeblood of innovation at the laboratories. Designed to pursue high-risk, potentially high-payoff research, this program provides the flexibility to anticipate and respond quickly to future national security needs while exploring potentially revolutionary scientific advances 4 .

Competitive Excellence

The funding is awarded through a rigorous competitive process focused on the forward-looking needs articulated by Sandia's mission areas and research initiatives 4 .

The LDRD program serves as a powerful recruitment tool, attracting top scientific talent who crave the opportunity to use leading-edge facilities in creative, potentially transformational research 4 . Some of the nation's most exciting innovations have roots in LDRD research, particularly in biological sciences where Sandia researchers are "focused on protecting soldiers and citizens from biological threats by creating innovative solutions" 4 .

Colorized X-Ray Imaging: Bringing the Invisible to Life

From Black and White to Living Color

The basic concept of X-ray technology has remained largely unchanged since Wilhelm Röntgen's pioneering work in the late 1800s—until now. A Sandia research team led by optical engineer Edward Jimenez, materials scientist Noelle Collins, and electronics engineer Courtney Sovinec has developed a revolutionary approach called colorized hyperspectral X-ray imaging with multi-metal targets (CHXI MMT) 1 .

Traditional X-rays are generated by bombarding a single metal target with high-energy electrons, producing a black-and-white image where denser materials like bones appear white and less dense tissues appear darker 1 . While useful, this approach limits resolution and clarity, providing limited information about an object's actual composition.

Traditional vs. Hyperspectral X-Ray Imaging

Far-Reaching Applications for Human Health

The implications for medical diagnostics are profound. "With this technology, you can see even slight differences between materials," Jimenez explains. "We hope this will help better identify things like cancer and more effectively analyze tumor cells" 1 .

The technology offers particular promise for mammography, where early detection of microcalcifications can be crucial. "In breast tissue, it's hard to identify the different dots, but with colorization you have a sharper beam and higher resolution image that increases the system's capability to detect a microcalcification," Jimenez notes 1 . This enhanced detection capability could lead to earlier diagnosis and more effective treatment of breast cancer.

Feature Traditional X-Ray Sandia's CHXI MMT
Image Type Black and white Colorized based on material composition
Focal Spot Larger, limiting resolution Smaller, creating sharper images
Information Content Density-based contrast Elemental composition and density
Target Material Single metal Multiple metals (tungsten, molybdenum, gold, etc.)
Detection Method Pattern recording Photon counting and energy measurement

Rapid Biothreat Detection: Nature's Own Alarm System

Harnessing Cellular Machinery for Pathogen Identification

While hyperspectral imaging reveals physical structures with new clarity, another Sandia innovation detects biological threats with unprecedented speed and specificity. Researchers Todd W. Lane and Richard W. Gantt developed a rapid detection system for biothreat agents that cleverly harnesses the specificity of cellular transcriptional machinery 2 .

The system capitalizes on a fundamental biological principle: bacterial cells contain RNA polymerases and transcription factors that recognize specific regulatory elements (promoters) upstream of genes 2 . These promoters are often recognized by polymerase and transcription factor combinations unique to a particular species.

Biothreat Detection Process
1
Preparation

Researchers engineer an E. coli indicator strain containing a plasmid with the virA promoter from Shigella flexneri fused to a GFP reporter gene 2 .

2
Mixing

The indicator strain is mixed with a sample potentially containing the target pathogen 2 .

3
Lysis

The cells are broken open, allowing their internal machinery to mix freely 2 .

4
Transcription Activation

If the target pathogen is present, its specific RNA polymerase and transcription factors recognize the virA promoter and initiate transcription of the GFP gene 2 .

5
Signal Production

GFP protein is produced, creating a fluorescent signal that confirms the presence of the biothreat agent 2 .

Step Process Outcome
1. Preparation Engineer indicator strain with plasmid containing pathogen-specific promoter fused to GFP reporter Creation of cellular "detective" that can identify specific pathogens
2. Mixing Combine indicator strain with test sample Potential contact between detector and target
3. Lysis Break open cells in the mixture Release of cellular machinery including RNA polymerases and transcription factors
4. Transcription Pathogen-specific machinery recognizes promoter and transcribes GFP gene Activation of cellular "alarm system"
5. Detection GFP protein produces fluorescent signal Visual confirmation of pathogen presence

Hyperspectral Fluorescence Microscopy: A Window Into Cellular Life

Another remarkable imaging technology emerging from Sandia's research portfolio is the hyperspectral confocal fluorescence microscope, which images hundreds of spectral wavelengths when obtaining spectral images 6 . This system combines advanced hardware with Sandia's unique proprietary multivariate algorithms and software to form a complete system for extracting quantitative image information from hyperspectral images at diffraction-limited spatial resolutions 6 .

The system's capabilities are extraordinary—it can reveal new fluorescent species that may not have been known to exist and allows expansion of the structural stains and molecular fluorophores that biologists can introduce into biological samples simultaneously 6 .

The Scientist's Toolkit: Research Reagent Solutions

The groundbreaking research at Sandia relies on a sophisticated collection of materials, methods, and technologies.

Multi-metal Patterned Anodes

Emit specific 'colors' of X-ray light based on metal composition.

Application: Elemental differentiation in colorized X-ray imaging 1

Energy-discriminating Detectors

Count individual photons and measure their energy.

Application: Material characterization in CHXI MMT system 1

Plasmid Vectors

Contain regulatory elements activated only by specific bacterial transcription machinery.

Application: Rapid detection of biothreat agents 2

GFP Reporter

Produces visible signal when activated by target cellular machinery.

Application: Visual confirmation of pathogen detection 2

MCR Algorithms

Analyze hyperspectral image data to identify and quantify emitting species.

Application: Extraction of quantitative information from hyperspectral images 6

Hyperspectral Microscope

Images hundreds of spectral wavelengths simultaneously.

Application: Detection of unknown fluorescent species 6

Conclusion: A Future of Enhanced Vision

The bioscience innovations emerging from Sandia's LDRD program represent more than incremental improvements—they constitute fundamental shifts in how we perceive and interact with the biological world. From colorized X-rays that reveal both structure and composition to cellular detection systems that harness nature's own recognition machinery, these technologies offer new ways to address persistent challenges in health and security.

As Noelle Collins, a member of the CHXI MMT development team, states: "From here we will continue to innovate. We hope to identify threats faster, diagnose diseases quicker and hopefully create a safer, healthier world" 1 . This commitment to exceptional service in the national interest—a core principle at Sandia since President Harry Truman—continues to drive research that transforms scientific imagination into practical solutions 3 .

The unseen is becoming visible, the undetectable is becoming apparent, and through these advances, we gain not just new technologies but new capabilities to protect, heal, and understand the complex biological systems that shape our world.

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