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  • Advances in Optical Filters Provide Rapid, On-the-Go Diagnosis

BioPhotonics
Apr 2015
Marie Freebody, Contributing Editor, marie.freebody@photonics.com

When it comes to diagnostics, one of the most crucial – and often overlooked – components is the optical filter. But as manufacturing processes improve, optical filters of exceptional quality are being created, which not only deliver accurate results but also open up an entirely new avenue of application in wearable diagnostics.

Optical filters are used to control the spectral content of a light beam, attenuate unwanted light and pass wanted light. Testing hemoglobin levels, monitoring blood glucose, detecting infectious diseases and cardiac and cancer markers require fluorescence, chemiluminescence, absorbance or Raman detection methods, all for which the optical filter is critical.

Optical glass filters now are made of high-quality materials and meet stringent specifications.
Optical glass filters now are made of high-quality materials and meet stringent specifications. Courtesy of Schott AG.


“Optical filters are an enabling technology. Unfortunately, sometimes they can be the last components considered by instrument developers, but it is just as important to consider the optical filter at the same time as one is considering which light source and optical detector to use to help properly optimize device performance from day one,” said Dr. Neil Anderson, business line leader at Semrock Inc. The company specializes in optical filters for life sciences, medical diagnostics and analytical instruments, and is based in Rochester, N.Y.

Filters have been steadily improving for the past two decades, and although the calculations for what filters could achieve were precise 20 years ago, production practices were not yet up to delivering such exacting quality, explains Dr. Ralf Biertümpfel, senior scientist and product manager of optical filters at Schott Advanced Optics. Based in Mainz, Germany, Schott develops and manufactures high-quality industrial specialty glass.

Modern interference filters made of hundreds of layers can comply with a very broad blocking of the spectrum and show a very high level of transmission.
Modern interference filters made of hundreds of layers can comply with a very broad blocking of the spectrum and show a very high level of transmission. Courtesy of Schott AG.


“We see the technological development towards a high level of material quality to be a recent one,” said Biertümpfel. “Today, filters are made of optical glass, which is of a very high quality and can meet high specifications such as an extremely high homogeneity. Modern interference filters made of many hundred layers can comply with a very broad blocking of the spectrum and show a very high level of transmission.”

As industrial techniques catch up with potential, we now see filters with intricate designs and ultrahard coatings manufactured with a high level of reproducibility. “They are much more filigree and can be coated in a large variety of ways to achieve a large number of product characteristics and application opportunities,” Biertümpfel said. “The quality of the coatings has also improved considerably in the last years.”

Spectrally complex sputtered optical filters of various sizes for use in PoC diagnostic instruments and devices.

Spectrally complex sputtered optical filters of various sizes for use in PoC diagnostic instruments and devices. Courtesy of Semrock Inc.


One of the most important advancements in optical bandpass filters was the development of all-dielectric sputtered coatings combined with innovations in non-quarterwave stack thin-film designs.

Sputtered hard-coated optical filters provide significant benefits due to the inherent stability of the coating over an extended period of time – in excess of 10 years, in fact, according to Anderson.

“Sputtered thin films also offer the highest level of spectral discrimination. That is, light transmission >95%, steep edges (<0.25% in the visible) and deep >OD6 blocking over an extended range of wavelengths,” he said. “With the miniaturization of point-of-care (PoC) diagnostic instruments, it is important to optimize thin-film coating to maintain a high level of spectral performance, especially when dealing with nonzero angle of incidence (AOI) light and the angular light distribution (cone half-angle) when LED light sources are used.”

Images depicting neurons stained with multiple fluorophores and DAPI+FITC+Texas Red filter sets from Iridian Spectral Technologies.

Images depicting neurons stained with multiple fluorophores and DAPI+FITC+Texas Red filter sets from Iridian Spectral Technologies. Courtesy of Iridian Spectral Technologies and NRC Ottawa.


As filter performance has improved significantly in recent years and costs are reduced, manufacturers like Robert Bruce, vice president of business operations at Iridian Spectral Technologies, located in Ottawa, Ontario, have noticed a new trend – the emergence of handheld Raman spectrometers and PoC analysis systems.

But as optical systems shrink and step outside of the laboratory, manufacturers must overcome a number of new challenges without compromising the optical output. Dr. Oliver Pust, director of sales and marketing of optical filters at Delta Optical Thin Film A/S, notes that the demand for high-performance filters is to meet the need for higher transmission, deeper blocking, steeper edges and larger angles. Based in Hørsholm, Denmark, Delta specializes in developing and manufacturing filters for the health and welfare sectors.

Modeling optical filter spectra for the fluorophore 5-FAM (5-carboxyfluorescein) in a PoC device application using SearchLight™.

Modeling optical filter spectra for the fluorophore 5-FAM (5-carboxyfluorescein) in a PoC device application using SearchLight™. Courtesy of Semrock Inc.


Accommodating larger angles is of paramount importance when it comes to PoC diagnostics, where the smaller optical setup requires wider angles to collect enough light.

“It is well known for fluorescence filters that their performance changes with AOI. With increasing AOI, the center or edge wavelengths shift towards the blue,” Pust said. “At the same time, polarization effects (i.e., splitting) occur. At Delta Optical Thin Film, we have special design and production technologies to minimize these adverse effects.”

PoC medical devices must be portable, small and robust for practical implementation. More importantly, they must provide a detection sensitivity that is at least equivalent to existing large “mainframe” instruments housed in commercial reference laboratories.

A small linear variable long-wave pass filter used as an order-sorting filter in mini spectrometers.
A small linear variable long-wave pass filter used as an order-sorting filter in mini spectrometers. Courtesy of Delta.


“With PoC, you cannot control how and where the instrument is being used (temperature, humidity, etc.). Therefore, you want environmentally stable filters that do not change their performance in different conditions and over time,” Pust said. “Our modern [ultrahard-coated] filters are ideally suited for this.”

While high-performance hard-coated optical filters initially were based on film properties, as PoC applications have grown to a level requiring tens of thousands to hundreds of thousands of spectrally complex fluorescence filters, there has been increasing focus on developing the right automated process technologies that allow parts to be manufactured to the highest standards of product quality, repeatedly and reliably, time and again.

PoC filters naturally have to be small (a few square millimeters). This means you must be able to dice the filters after the coating process without damaging them, which has only been made possible with the most recent production technology.

Linear variable short-wave pass filters.
Linear variable short-wave pass filters. Courtesy of Delta.


Optical filters of the future

The future of optical filter requirements ultimately will be driven by the needs of the end application. With the increasing number of tests expected to be incorporated into PoC applications, the need for high-performance fluorescence filters with a degree of spectral discrimination – such as high-percentage transmission and deep extended blocking – will continue.

Forming a tunable bandpass filter using a short-wave pass and a long-wave pass linear variable filter.
Forming a tunable bandpass filter using a short-wave pass and a long-wave pass linear variable filter. Courtesy of Delta.


Another trend to look out for is the development of assays that perform more than one test. Rather than multiple single-band optical filters, there is a growing need for multiband versions.

“This is where sputtered deposition technologies coupled with state-of-the-art deposition monitoring allows the production of parts having steep passband edges and deep blocking that help to minimize signal bleed-through across channels,” Semrock’s Anderson explained. “The latter is undesirable for accurate PoC testing, as the true signal to be collected becomes contaminated with out-of-band light.”

Consumers also will play a role in shaping the optical filters of the future as the popularity of wearable diagnostics grows. Today’s shoppers already have a plethora of options when it comes to wearable devices that can monitor a person’s vital signs, such as heart rate while exercising. Next-generation devices could incorporate near-infrared light sources to enable them to perform diagnostic tests noninvasively, with test results wirelessly transmitted to your personal physician. Miniaturization driven by cellular imaging could lead to PoC devices the size of a USB stick, predicts Anderson. In this case, an alternative to traditional fluorescence filter cubes may be required – such as a monolithic, all-glass “supercomponent.”

Optical filter manufacturing in an ISO 9001:2008 facility.
Optical filter manufacturing in an ISO 9001:2008 facility. Courtesy of Semrock Inc.


“With each individual excitation, dichroic and emission filter coating deposited on one of the glass surfaces, it would be possible to mimic a traditional filter cube arrangement without the bulky mechanical mounting scheme typically required,” said Anderson. “Future development in thin-film design and volume manufacturing processes will continue to be driven by the vision and innovative thinking of instrument developers. It will be exciting to see what tomorrow brings!”

Meet the author

Marie Freebody, a contributing editor for BioPhotonics, is based in Bournemouth, U.K.; email: marie.freebody@photonics.com.



Top applications of PoC testing:

Imagine being rushed to the hospital with chest pains and loss of feeling on one side – a terrifying experience and one where PoC diagnostics could mean the difference between life and death.

The advantage of making an accurate and reliable medical diagnosis near the patient saves valuable time, allowing for prompt and sometimes lifesaving treatment, and also can help to avoid longer hospital stays. For some, it is the only option for diagnosis in areas where sophisticated medical facilities are unavailable.

Top four applications of PoC diagnostics:

1. Blood glucose testing (diabetes): Diabetes monitoring makes up the largest segment of the PoC market, estimated at over $10 billion and growing by around 8 percent through 2016. According to IDF Diabetes Atlas (6th Ed., 2013), around 328 million people are living with diabetes worldwide (46 percent undiagnosed). Refined foods and reduced exercise levels are to blame for contributing to an expected 55 percent rise in the number of cases by 2035.

2. Infectious disease testing: Illnesses include influenza (responsible for greater than 200,000 hospitalizations in the U.S. and 36,000 deaths annually worldwide) and HIV/AIDS (

estimated to affect around 33 million people worldwide with the largest concentration in sub-Saharan Africa, according to the 2010 U.N. AIDS epidemic update, 2009). 3. Cardiac care: Rapid, near-patient testing for suspected heart attacks can help reduce overcrowding in hospital emergency rooms. A study by Trinity Biotech revealed that PoC cardiac troponin testing resulted in savings of around $4200 per patient admission.

4. PoC testing in developing countries: Patients in developing countries often lack access to even the most basic medical testing methods. This is a central motivation to many involved in creating PoC devices/instruments that address the health care needs of many of the world’s poorest people. Organizations like the Bill & Melinda Gates Foundation play a pivotal role by funding research to develop easy-to-use diagnostics that can be readily deployed en masse in remote settings.


GLOSSARY
fluorescence
The emission of light or other electromagnetic radiation of longer wavelengths by a substance as a result of the absorption of some other radiation of shorter wavelengths, provided the emission continues only as long as the stimulus producing it is maintained. In other words, fluorescence is the luminescence that persists for less than about 10-8 s after excitation.
chemiluminescence
A chemical reaction involving the production of light. The reaction of ethylene with ozone is chemiluminescent.
absorbance
The natural log of the ratio of absorbed intensity over the total intensity which gives a constant value assuming a stable volume as well as energy. In optical physics the absorbance may be defined as the absorption cross section multiplied by the absorbing material length.
thin film
A thin layer of a substance deposited on an insulating base in a vacuum by a microelectronic process. Thin films are most commonly used for antireflection, achromatic beamsplitters, color filters, narrow passband filters, semitransparent mirrors, heat control filters, high reflectivity mirrors, polarizers and reflection filters.
dichroic
Exhibiting the quality of dichroism.
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