3D-Printed Microscope for Medical Diagnostics

3D view of a green algae sample imaged with the microscope, showing that the 3D structure was captured. (Source: B. Javidi, U. Connecticut)

Researchers have used 3D printing to make an inex­pensive and portable high-resolution micro­scope that is small and robust enough to use in the field or at the bedside. The high-resolution 3D images provided by the instrument could poten­tially be used to detect diabetes, sickle cell disease, malaria and other diseases. “This new micro­scope doesn’t require any special staining or labels and could help increase access to low-cost medical diagnostic testing,” said research team leader Bahram Javidi from the Uni­versity of Connecticut. “This would be especially beneficial in deve­loping parts of the world where there is limited access to health care and few high-tech diagnostic faci­lities.”

The new microscope is based on digital holo­graphic micro­scopy. The portable instrument produces 3D images with twice the resolution of tradi­tional digital holo­graphic micro­scopy, which is typically performed on an optical table in a labora­tory. In addition to biomedical appli­cations, it could also be useful for research, manu­facturing, defense and education. “The entire system consists of 3D printed parts and commonly found optical components, making it inex­pensive and easy to replicate,” said Javidi. “Alter­native laser sources and image sensors would further reduce the cost, and we estimate a single unit could be reproduced for several hundred dollars. Mass pro­duction of the unit would also substan­tially reduce the cost.”

In traditional digital holo­graphic micro­scopy, a digital camera records a hologram produced from inter­ference between a reference light wave and light coming from the sample. A computer then converts this hologram into a 3D image of the sample. Although this micro­scopy approach is useful for studying cells without any labels or dyes, it typically requires a complex optical setup and stable environ­ment free of vibrations and tempera­ture fluc­tuations that can introduce noise in the measure­ments. For this reason, digital holo­graphic micro­scopes are generally only found in labora­tories.

The researchers were able to boost the reso­lution of digital holo­graphic micro­scopy beyond what is possible with uniform illu­mination by combining it with a super-resolution technique known as structured illu­mination micro­scopy. They did this by generating a structured light pattern using a clear compact disc. “3D printing the micro­scope allowed us to precisely and perma­nently align the optical components necessary to provide the resolution improve­ment while also making the system very compact,” said Javidi.

The researchers evaluated the system perfor­mance by recording images of a resolution chart and then using an algorithm to reconstruct high-resolution images. This showed that the new micro­scopy system could resolve features as small as 0.775 microns, double the reso­lution of tradi­tional systems. Using a light source with shorter wavelengths would improve the resolution even more.

Additional experi­ments showed that the system was stable enough to analyze fluc­tuations in biological cells over time, which need to be measured on the scale of a few tens of nanometers. The researchers then demon­strated the applica­bility of the device for biological imaging by acquiring a high-reso­lution image of a green algae. “Our design provides a highly-stable system with high-resolution,” said Javidi. “This is very important for examining sub­cellular structures and dynamics, which can have remarkably small details and fluc­tuations.”

The researchers say that the current system is ready for practical use. They plan to use it for biomedical appli­cations such as cell identi­fication and disease diagnosis and will continue their colla­boration with their inter­national partners to inves­tigate disease identi­fication in remote areas with limited health care access. They are also working to further enhance the reso­lution and signal-to-noise ratio of the system without increasing the device’s cost. (Source: OSA)

Reference: T. O’Connor et al.: Structured illumination in compact and field-portable 3D-printed shearing digital holographic microscopy for resolution enhancement, Opt. Lett. 44, 2326 (2019); DOI: 10.1364/OL.44.002326

Link: Biomedical Engineering Dept., University of Connecticut, Storrs, USA

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