A team of scientists, including Johns Hopkins engineers and clinicians, has unveiled a high-speed microscope that delivers unprecedented views of living tissues and flowing blood cells without using any dyes. The new technique, called Back-Illumination Tomography (BIT), images unprocessed tissue in real time using reflected light.
Described in the journal Optica, BIT has the potential to enhance medical research by allowing scientists and doctors to observe biological processes as they happen inside the body. Such observation could be instrumental in studying and diagnosing conditions like sickle cell disease, cancer, and cardiovascular diseases.
Current microscopes struggle to capture clear, real-time images within thick, dense tissues and are too slow to track fast-moving objects at high-resolution, such as blood cells.
“BIT involves a simple modification to a microscope that reveals subtle tissue structures,” said Nicholas Durr, an associate professor of biomedical engineering and the paper’s senior author. “With a high-speed camera, we show that BIT can image flowing blood cells in vivo [inside a living organism]. We also show that BIT can directly image 3D pathological features in unprocessed tissues, bypassing the conventional histology steps of fixation, slicing, and staining.”
Lead author Gregory N. McKay, a surgical resident at Johns Hopkins Hospital, developed the system alongside Durr. Their solution is far more effective than current microscopes at capturing moving targets and capturing detailed volumetric images of unprocessed tissues. By providing instant visualization, the technology could eliminate the traditional hours or days spent waiting for lab results, allowing clinicians to identify diseased tissue on the spot and accelerate patient care.
The team explains that BIT captures biological structures usually hidden from view by enhancing the contrast of “weakly scattering” elements. The new microscope doesn’t rely on multiple lasers, scanning beams, or extensive computational analysis like older models. Instead, BIT achieves its detailed images by creating a small virtual source within the tissue and imaging the backscattered light. When light interacts with cellular components—such as the nucleus or cell membrane—it scatters and recombines with the background field to produce a high-contrast interference pattern that reveals internal structures.
The team hopes that as the BIT system evolves, it will provide the instant, cellular-level views needed to uncover vital new information and drive progress in fields from cancer treatment to drug development.
“The goal is to start shifting medicine away from methods that rely on lengthy laboratory testing toward real-time diagnostics,” said Durr.
The researchers are now focused on refining the technology and developing methods to combine images from different angles into accurate 3D views of tissue. Ultimately, they hope to use this data with artificial intelligence to generate “virtually stained” images that could someday assist clinicians in making a diagnosis.
Jerome Mertz, a professor of biomedical engineering at Boston University, also contributed to the study. The research was supported by the Gates Foundation and Fifth Generation Inc.