Raman technique enables noninvasive blood test

Researchers at the Massachusetts Institute of Technology (MIT; Cambridge, MA) have developed a five-minute noninvasive blood test that uses 830-nm light from a laser diode to identify the concentration of nine critical components in a blood sample. It is believed to be the first time that a single technique has quantitatively measured such a large number of compounds simultaneously in whole blood.

"Reliable clinical diagnosis requires multiple blood parameters to be analyzed, often involving a series of analyte-specific procedures, including adding various reagents," said Michael Feld, director of the Laser Biomedical Research Center of the George R. Harrison Spectroscopy Laboratory. "This necessitates the withdrawal of several blood samples associated with extensive administration of the sample handling, delay in the diagnosis process, exposure to biohazards for personnel, and inconvenience to the patient."

Feld and his team have spent the last several years developing a Raman spectroscopy technique for noninvasive blood analysis and recently conducted some clinical tests on humans. "A Raman spectrum provides molecule-specific information," Feld explained. "By combining Raman spectroscopy and hybrid linear analysis, we have demonstrated that concentrations of multiple analytes in human whole blood can be measured with clinical accuracy."

Because Raman spectra are composed of sharp and distinct features characteristic for each molecule, one analyte can easily be distinguished from another, as well as from a broad fluorescence background. Thus, the MIT researchers optimize the sensitive Raman instrumentation for the turbid character of tissue and apply and develop multivariate analysis techniques to extract the subtle signals generated by the analytes.

Feld's team performed the multicomponent test on 31 patients in a Boston hospital to measure concentrations of glucose, urea, total protein, cholesterol, albumin, bilirubin, triglycerides, hematocrit, and hemoglobin. All but bilirubin and cholesterol could be detected with enough precision for clinical use, Feld said.

When the researchers discovered that the turbidity of blood caused scattering patterns that could not be collected efficiently using conventional optics, they optimized the collection optics with optical design software. They then introduced a gold-coated half-paraboloid mirror into the setup. According to Feld, this 15.9-mm focal-length mirror collects about 25% of the total Raman-scattered light from the blood, making it approximately four times more efficient than conventional lenses used in a previous system.

In the test, 30 consecutive spectra of each sample were taken over five minutes, with conventional clinical methods used to calibrate the Raman test. A charge-coupled-device detector captured the scattered light that contained the necessary spectral information to determine each concentration. Feld believes that this technique is suitable for clinical use. He and his research team have focused on using it for detecting glucose levels for diabetes monitoring and for detecting abnormal cells in cancer research, as well as to perform such tasks as examining and classifying various kinds of coronary arteries with greater than 94% accuracy.