Jane Anderson
May 23, 2012

A blood test without needles: Optical microscopy looks directly at blood cells through the skin

An in vivo image showing blood cells in a microvessel. The area occupied by red blood cells in the images is used to calculate the percent volume of blood cells, a key measurement for diagnoses. Credit: Biomedical Optics ExpressEventually, a device no bigger than your thumb could perform routine blood tests, without the need for needles, by using an optical microscope that shines a light through the skin to look directly at blood flowing through capillaries. The Israel Institute of Technology (Technion) researchers developing the device say they already have used their prototype to measure several key components of blood cell health.

The prototype device, currently around the size of a shoe box, relies on a technique called spectrally encoded confocal microscopy (SECM). It enables researchers to determine characteristics of individual blood cells by projecting a beam of light into them.

SECM creates images by splitting a beam of light into its color spectrum components. Researchers press a probe against the skin of a patient, and the light beam shines across a tiny blood vessel just below the skin’s surface. When blood cells cross the beam of light, they scatter the light’s rays. The researchers collect that light-based data and then use computer programs to translate it into 2-D images of the blood cells.

“We have invented a new optical microscope that can see individual blood cells as they flow inside our body,” said Lior Golan, a Technion graduate student working on the project. Golan and four co-authors published a paper describing the device this week in the open-access journal Biomedical Optics Express.

Blood draws for routine blood tests are minor but invasive procedures that can be exacerbated by patients’ fears of needles and the need for repeated tests. Various researchers have explored approaches for noninvasive blood monitoring by using ultrasound waves or electricity, but the techniques haven’t proven to provide precise measurements, and often are hampered by relatively low spatial resolution.

Studies also have explored using fluorescent dyes that are injected into the bloodstream to illuminate the specific blood components for viewing under a microscope, but those dyes could be harmful to patients.

The team’s device relies on spectrally encoded confocal microscopy. (a) A single line within a blood vessel is imaged with multiple colors of light. (b) A single cell crossing the spectral line produces a two-dimensional image with one axis encoded by wavelength and the other by time. Credit: Biomedical Optics ExpressTo demonstrate their technique, the Technion researchers used the device to image the blood flowing through a capillary in the lower lip of a healthy volunteer. They found their SECM approach was able to identify and classify different types of leukocytes within the capillary, calculate the percent volume of the different cell types, and to show cellular flow dynamics with submicron resolution. The results from the SECM device correlated with results from conventional blood testing, the researchers said.

The device was able to detect blood vessels at depths ranging from 70 μm to 200 μm under the tissue surface by using a separate green LED light and a camera, which the researchers then incorporated into the system. Green light makes blood vessels appear dark, since hemoglobin absorbs light.

Each imaging session lasted only about 30 seconds, mainly because the subject had to sit very still for the device to work.

The device’s ability “to directly and continuously visualize blood cells flowing inside human patients' vessels has the potential of providing noninvasive measurement of important blood parameters such as hematocrit, mean corpuscular volume (MCV) and WBC [white blood cell] count, as well as for establishing new clinical indices derived from the cells' morphology and dynamics within their natural physiological environment,” the researchers said in their paper. “Continuous tracking of hematocrit levels could be useful for intra- and post-surgical monitoring of patients for detecting sudden changes in the circulation caused by internal bleeding, for example, and online monitoring of WBC concentration could be highly useful in critical care to detect a rapidly developing inflammatory process.”

The device is merely a prototype in its earliest stages, and it is years away from any clinical application, the Technion researchers cautioned. Work has begun on a second generation system that the researchers hope will have the ability to beam deeper into the body, which might expand the possible imaging sites beyond the inside lip. The lip was chosen initially because it’s a blood vessel-rich site that doesn’t contain any pigment that might block light, and because trauma patients don’t lose blood flow in their lips.

Golan said the team hopes to have a thumb-sized prototype in the next year.

Other researchers are experimenting with new techniques that might allow physicians to “see” blood cells beneath the skin. For example, photoacoustic tomography -- a technique that pairs the light absorption of colored molecules such as hemoglobin with the spatial resolution of ultrasound -- might allow physicians to examine lymph nodes in breast cancer patients without the need for dye tests or invasive procedures.


Golan L. et al. Noninvasive imaging of flowing blood cells using label-free spectrally encoded flow cytometry. Biomedical Optics Express. Published online 21 May 2012.