WASHINGTON — Researchers have developed a compact, handheld mid-infrared imaging spectrometer that can produce high-resolution chemical maps of a sample without using any stains or labels. With more development, the handheld device might provide a portable and easy-to-use way to map the molecular makeup of tissues and other samples.
"Ultimately, this technology could make it possible to assess tissue during cancer surgery," said research team leader Rohith Reddy from the University of Houston . "After removing a suspected tumor, a surgeon could scan the freshly excised tissue to help determine whether it is malignant or whether cancer cells remain at the surgical margin. This complementary information would be available while the patient is still in the operating room instead of having to wait for results from laboratory testing."
In Optica , Optica Publishing Group 's journal for high-impact research, the researchers describe how they transformed a photothermal mid-infrared spectroscopic imaging (MIRSI) system, normally a benchtop instrument occupying more than 9 square feet, into a handheld probe measuring 8 by 8 inches. The probe holds the full optical head and connects by a flexible fiber tether to a compact base unit housing the lasers and control electronics. In side-by-side tests, it delivered image quality and chemical detail comparable to a state-of-the-art benchtop MIRSI system.
"Although the current platform is still a research prototype, it establishes a technical foundation for field-deployable, label-free chemical imaging," said Reddy. "A handheld MIRSI device could be useful for clinical diagnosis, polymer manufacturing, pharmaceutical quality control, forensic analysis or any applications where chemical composition must be measured outside a specialized laboratory."
Shrinking a bulky lab instrument
Photothermal mid-infrared spectroscopic imaging systems map the molecular composition of tissue or other samples, showing where different biochemical components are located. Because molecules absorb mid-infrared light at wavelengths determined by their molecular bonds, they produce characteristic spectra that can be used to distinguish proteins, lipids, nucleic acids and other components.
Unlike conventional infrared imaging, which typically uses infrared light itself to form an image, photothermal imaging detects tiny heat-induced changes caused by infrared absorption. Although this approach produces high-resolution chemical images, it typically requires a large laboratory-based instrument.
"Our initial goal was to determine whether a compact design could preserve the laboratory system's essential capabilities," said Reddy. "The resulting platform was even closer in size and form to a clinically deployable device than we initially expected, providing a strong foundation for future clinical translation."
Miniaturizing a photothermal MIRSI instrument is especially challenging because it requires visible and mid-infrared light to be focused onto the same point. These two wavelength ranges generally require different optical materials because materials that work well for visible light often absorb mid-infrared light, while those that work for mid-infrared light can introduce dispersion and other wavelength-dependent distortions that degrade the signal.
To create a compact and flexible MIRSI system, the researchers used chalcogenide optical fibers to deliver mid-infrared light directly from the laser, eliminating bulky free-space optics. They also replaced traditional lenses with mirrors. Because mirrors can reflect both visible and mid-infrared light, this allowed the two beams to share the same optical path without requiring a lens material that transmits both wavelengths. A final off-axis parabolic mirror was used to focus both beams onto the sample, and raster scanning was also introduced into the optical system."
"Careful optical design and alignment helped to minimize the image distortions that mirrors can cause," said Reddy. "We also designed the handheld scanner to connect to the light source through a fiber-optic cable, allowing it to be maneuvered easily around a sample."
Validating the handheld system
The researchers evaluated their handheld system using biological samples, including human cervical and ovarian cancer tissues, human bone marrow biopsy tissue and mouse kidney tissue. To provide controlled tests of the system's chemical specificity, they also characterized PMMA and polystyrene, polymers with distinct mid-infrared signatures. They then analyzed the same samples using a state-of-the-art benchtop chemical imaging system.
The researchers found that the spectra and images acquired with the handheld system exhibited comparable chemical contrast and imaging performance to the benchtop chemical imaging system, demonstrating that miniaturization successfully preserved the technology's core capabilities.
The system resolves features as small as 2 µm, five times finer than direct infrared detection allows, and matches or exceeds current benchtop instruments on both spectral and spatial performance. Spectra of biological tissue agreed with reference FTIR measurements at a cosine similarity of 0.935, and chemical images correlated with the benchtop system at r = 0.90.
The researchers are now working to broaden the system's mid-infrared spectral bandwidth – currently 1150 to 1400 cm−1 – to provide more complete molecular signatures and improve the system's ability to distinguish different biochemical constituents. They also plan to increase the imaging speed, which would help reduce motion artifacts and make true freehand operation more practical for clinicians and technicians. They note that before clinical use, the system's repeatability, safety and diagnostic performance must also be thoroughly evaluated under realistic clinical conditions.
