Purdue University System Could Eliminate Blood Draw in Some Clinical Tests

NEW YORK (360Dx) – It will likely take another five years to accomplish, but researchers are developing an imaging and probe system that could eliminate the need to draw blood in some routine diagnostic tests.

The system — being developed by the Purdue University Weldon School of Biomedical Engineering and XiDian University in China — uses a laser beam to penetrate deep into human tissue. It looks for accumulation of small-molecule lipids and hemeproteins that may be useful biomarkers in tests for conditions such as prostate cancer, breast cancer, and arteriosclerosis, a precursor to heart disease, said Chi Zhang, a postdoc at Purdue's Weldon School of Biomedical Engineering who is developing diagnostic tests with colleagues.

The researchers noted that an important component of the system that generates a Bessel beam can be produced using fibers, which could simplify the system and enable endoscopic applications.

The developers described their work in a paper published online recently in the journal Nature Communications.

Zhang said that it will take some time to complete further development work on the system, especially related to reducing the price of some of its components, but it is "technically feasible" to build a diagnostic instrument that uses the imaging system for routine clinical use.

The system uses an adaptation of traditional stimulated Raman projection microscopy that produces 2D images of tissue and enables molecular analysis, he said.

Its Bessel beam penetrates deeper into tissue than a Gaussian beam that's frequently used in imaging technologies, he said. The researchers get to an image of a 3D structure by combining the beam with a tomography system that enables the collection of cross-section tissue images.

This is done by rotating the tissue and using a reconstruction algorithm to add signals generated by the 2D slices to construct a 3D structure.

Ji-Xin Cheng, a lead researcher working with Zhang, and a visiting scholar at Purdue from Xidian University, said in a statement that by leveraging deep tissue imaging, the technology could lead to diagnostic systems that eliminate the need to draw blood for detecting biomarkers and enable non-invasive early diagnosis of diseases.

The system's use for volumetric fluorescence imaging was previously demonstrated by physicist Eric Betzig, who won the Nobel Prize in chemistry in 2014 for his contribution to super-resolution fluorescence microscopy. Super-resolution technology allows researchers to resolve structural features far smaller than the wavelength of visible light, sidestepping the diffraction limit that normally prevents imaging of features smaller than about 250 nanometers, which is large compared to certain biological molecules and structures in cells.

Zhang noted that the researchers are developing a fiber probe to generate a Bessel beam that could be used in endoscopic procedures and inserted into arteries to obtain internal images of plaque buildup indicative of artery disease that could lead to cardiac events or stroke.

More broadly, the system enables analysis of the chemical composition of 3D complex biological systems such as cells, Zhang said. The potential of the system to eliminate a blood draw for some cancers and infectious diseases is one potentially advantageous feature, the researchers said.

Another important advantage is that it eliminates the need to use fluorescent dyes used as molecular labels in diagnostic tests. Dies are not only toxic, but they can also have a detrimental effect on the accuracy of diagnostic tests. "There's no perturbance to cellular functionality" with the Purdue system, Zhang said.

The system could prove useful as a diagnostic tool that improves clinical care in invasive as well as non-invasive medical procedures, Zhang said, adding that one of the applications they are evaluating addresses an "unmet need related to breast cancer surgery." A successful tissue biopsy taken from a patient suspected of having breast cancer consists of normal tissue surrounding the tumor. The Purdue chemical imaging system could be used to recognize whether normal tissue is present or not.

"Normal breast tissue has a greater volume of lipids that our system can detect," Zhang said, adding that the technique can therefore be used to indicate whether the biopsy has been successful. Cancerous cells at the margin of the sample, on the other hand, may indicate that the patient needs to return for another surgical procedure, he added.

Although the team is currently studying the potential to apply the diagnostic test to breast and prostate cancers, they will likely evaluate its potential for use in the diagnosis of other cancers in the future, Zhang said.

The team is also developing diagnostic devices for infectious disease testing. For that it is using the traditional form of stimulated Raman microscopy. "We're using it to evaluate the potential to get global information related to the drug resistance of infected 3D samples," Zhang said.  

Although promising, Purdue's chemical imaging system is, nonetheless, still a lab tool, Zhang noted, adding that it may take five years to develop a "robust and user-friendly diagnostic system."

"To generate the Bessel beam, all we need are two axicon lenses," he said. "For imaging, the scanning method is similar to what's used in conventional stimulated Raman projection microscopy. Thermography is a little more complicated and requires rotating the sample, but we are using commercially available technology used in other fields."

"There is plenty of room for improvement," Cheng said. "The system is based on a bulky and relatively expensive femtosecond laser, which limits its potential for broad use and clinical translation. Nevertheless, we anticipate that this limitation can be circumvented through engineering innovations to reduce the cost and size of our technology." Future research will include work to increase the detection sensitivity of the system and improve the imaging quality and speed, Purdue said.

The Purdue group is, simultaneously, making commercial progress with a separate imaging system that employs photoacoustics to probe for cholesterol-generating plaque in arteries.

They have established a company, Vibronix, that's collaborating with Indiana University Hospital to evaluate its clinical utility.

The research involving a Bessel laser beam was supported by funds from the Keck Foundation and National Institutes of Health.