DNA samples in a thermocycler

A CLOSER LOOK AT THE ENABLING OPTICAL TECHNIQUES

Scientific and engineering teams are collaborating worldwide to develop the molecular testing tools essential for detecting the presence of the COVID-19 virus and the associated antibodies after the immune system has fought off the disease. In the predominate methods such as polymerase chain reaction (PCR), immunocytochemistry, and ELISA, a fluorescent reporter is used to label the target of interest. Optical imaging and detection are the de facto standard methods for measuring and quantifying a wide range of molecular testing techniques.

PCR is a technique used to read nucleic acids, an essential tool for unlocking genetic codes in a wide variety of cellular systems, including viruses. A key element detecting the presence of a virus through PCR techniques is to make many copies of the DNA/RNA of interest. The amplified signal can then be quantified optically using fluorescent tags, one tag for each genetic signature.  When the viral genetic signatures are detected, a diagnosis can be made. In COVID-19 detection, PCR looks for the specific genetic (RNA) information that corresponds to the virus.

PCR systems, typically found in high-throughput testing laboratories, are now entering the market as portable, point-of-care devices for use at the bedside and at drive-through COVID-19 testing sites and even as at-home tests measured using a smart phone. While each type of device has differing levels of sophistication, the optical systems within each device are critical to producing an accurate result.

Once a person has recovered from COVID-19, the body produces several types of antibodies to fend off future infections. Enzyme-Linked Immunoabsorbent Assay (ELISA) is a test method that looks for the presence these antibodies in a blood sample. The optical systems within an ELISA device use either conventional fluorescence or colorimetric signal measurement to quantify the result.  High quality optics are again an essential part of providing rapid and reliable results.

Optics in Point-of-Care Medical Devices

Innovations in handheld diagnostic devices continue to hit the market to help in the fight against COVID-19. For example, small portable tests can be used at home to analyze sputum samples for the detection and identification of viruses that impact lung function. Once a sputum culture is collected, it is applied it to a test strip and is run through an assay to detect the virus signature. Through a custom optical detector, the chip communicates the results to the user’s smartphone.

As viral detection depends on quantifying the amount of target probe activated in a sample, linearity and signal to noise (SNR) of the measurement is crucial. The efficiency and stray light management within the optical design is key to achieving high SNR and yielding a test with suitable levels of sensitivity and specificity.

In a typical PCR device, the optics consist of a set of lenses used for focusing light to excite a fluorophore and for collecting the emitted light from the sample. High quality spectral filters are used to tailor the wavelength profile for optimal excitation and detection of the emitted fluorescence. The fluorescence signal is detected through a photo detector or a CMOS or CCD camera, depending on the degree of multiplexing within the optical system. Traditional, off-the-shelf optics are not typically adequate to meet the demanding performance requirements of these systems. Custom designed precision optics provide the performance and sensitivity these systems require.

In camera based diagnostic systems, alignment of the sample to the sensor and image focusing are typical challenges. In the optical design, optimizing parameters such as field-of-view, depth-of-field, and the lens f/# are key to achieving the required performance.

The specification and design of the fluorescence excitation and emission filters are also key to device performance. The filter spectral profile must be appropriately matched to the fluorophore properties. The coating design must also be designed in conjunction with the optical system to ensure that the light angles of incidence match. A common problem in fluorescence detection is angular mismatch, leading to bleed-through of light which degrades the system SNR.

Finally, manufacturing diagnostic devices with precision optical components at scale is a unique challenge. From a product development standpoint, companies must find a way to reduce costs in order to meet the demand for these systems. Particularly in the life sciences space, a new technology can be proven out with off-the-shelf parts and prototypes, but it’s not going to reach the market because it’s too expensive to make and therefore very difficult to scale. For a safe, high-quality, commercially viable product to succeed, it must meet both manufacturability and cost targets.

Design for manufacture is at the heart of what we do. Let our product development team help you reduce cost, size, weight of your diagnostics system, all while improving its performance through expert optical engineering. Get started by contacting our engineers.

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