This overview is the introductory essay to the Filters, Membranes, and Bioseparation Equipment section of the 2012-2013 Buyers Guide.
IVD technology continues to advance, adding new biomarker detection capabilities, refined sample sensitivity, and test applications in areas such as food safety, animal health, and infectious diseases. As they keep pace with these changes, suppliers of membranes and filters emphasize that buyers for these components must understand certain fundamental requirements if they are to get the most out of their assays.
Assay efficiency requires the diagnostic device to use a membrane “that is appropriate for that particular application, depending primarily on sample type and analyte of interest,” says Chris Wilkins, vice president of marketing, lab and diagnostics, Pall Life Sciences (Ann Arbor, MI).
Wilkins says the nature of the analyte and the level of sensitivity required will dictate which membrane is the right one. Membrane selection “can be so application- and assay-dependent,” he says, noting that the goal is “getting enough purified analyte for increasingly more sensitive assays.”
Once the device company determines the nature of the sample, it is important to decide the chemical compatibility of the membrane for the type of purification required, says Wilkins. “Can the target be selected based on charge or size? Based on the nature of the molecule, there are a variety of different things that can done.” For instance, Pall makes a filter plate designed specifically for use with bead-based assays.
Wilkins says diagnostics technology is following the overall miniaturization trend, where smaller samples and instrumentation require more sensitive means of detection. The amount of plasma required from a blood sample is one example. “If you’re talking about lateral-flow devices, developers want more and more plasma, and they want it quicker and cleaner than before,” he says.
“In terms of filter material for IVD requirements, the most common—the gold standard—of lateral flow diagnostics kits is nitrocellulose materials,” says Shawn Gaskell, product manager, membrane products, EMD Millipore (Billerica, MA). “That’s been around for many years. It’s really the foundation on which all these kits are developed. Going forward, there’s a desire and need from the industry to be able to prepare these materials in a more consistent and homogenous manner, which will allow the market to deliver more sophisticated and exact tests for these platforms.”
This growing sophistication is fueling a rise in the use of quantitative testing, particularly as mobile and OTC tests become more popular, Gaskell says. “Urine-based tests are pretty easy to use with large samples. When you have saliva or even blood and are looking for certain types of proteins or material in the [sample] itself, it can be more difficult to get the right concentration or amount of material you’re trying to measure. That is a part of the growing sophistication of the market as these tests become more involved.”
Ben Ward, vice president of R&D at Filtrona Porous Technologies (Colonial Heights, VA), says that customers primarily need their IVD device “to move liquid from Point A to Point B effectively without modifying the analyte to be tested.” If it’s a membrane, the filtering media can be made of materials ranging from cast polysulfone to sintered plastics with a certain degree of porosity, he says.
“Typically, if you’re looking for filter media for a specific application, the filter media provider would want to know what the customer requirements are with respect to the particulate that’s being filtered out,” Ward says. “Is it a virus? Is it bacteria? Is it random particles?”
After identifying particulate type, knowing the particle size and the efficiency rate are important metrics for determining the proper media, Ward says. Customers typically require a device “that will filter out a selected particle size at a determined efficiency rate, targeting filtration of a 5-micrometer particle at 99%-plus efficiency, for example.”
IVD devices that are filtering liquids can “run into a phenomenon called pressure loss, where it takes a certain amount of force to pass liquid through the filter,” says Ward. “If you don’t have the capacity to supply added pressure [in the device], that can cause the device to fail. It’s also important to know what the pressure loss, or pressure drop, is.”
Filtrona receives requests “to filter out the extraneous or bad stuff” from the samples used in their devices, Ward says. As an example, he says Filtrona produces a saliva-collection media for POC drugs-of-abuse testing. The test device containing the media is placed in the subject’s mouth, absorbing oral fluid and “whatever else happens to be in the person’s mouth at the time.” The saliva collection media reduces the viscosity of the oral fluid, Ward says. “A lot of drug abusers suffer from dry mouth, and their saliva is viscous,” he notes. “Our collection media reduces viscosity, removes extraneous particulates, and makes [the sample] easier to test.”
Nonspecific binding is a common issue in almost any diagnostic device, Ward says. Any media or component that delivers fluid “from Point A to Point B needs to have a very low level of nonspecific binding.” Nonspecific binding “tends to remove the analyte of interest from your sample.” As a result, too much of the analyte is lost and device sensitivity suffers.
“You want to work with a company that’s developing filtration or wicking media with a variety of technologies to mitigate or minimize nonspecific binding,” Ward says. The type of polymer or material used to construct the media and the technologies used for surface passivation is essential. Surfactants, chemical treatments, or a combination of the two can be used on the selected media in order to ensure the lowest possible level of nonspecific binding, he says.
One future trend is the use of microfluidics technology in IVD devices, Wilkins says. The technology will be used in “more hands-free types” of devices with smaller footprints and the ability to test “smaller and smaller” sample volumes. This will complement lateral-flow technology, which is the mainstay for pregnancy, cholesterol, diabetes, and other POC tests as microfluidics technology awaits broader acceptance, according to Wilkins.
IVD suppliers are continually looking to shrink complex equipment and move it to the point of care, Wilkins says. It’s a matter of taking tests that require complex analysis, putting them “onto a simple card, and getting yes-no answers,” he adds. The key is “hitting the right applications and the right markets at the same time.” Agricultural tests related to food safety are one example of a large growing market, according to Gaskell. They’re targeting not only consumers but also upstream corporations and farmers who can test their crops for molds before harvesting.
Given the trajectory of IVD technology, membrane and filter suppliers are adapting to new challenges to meet customer needs. Although 70% of EMD Millipore’s sales are for off-the-shelf products, Gaskell says suppliers should know how to develop customized materials at the right cost “within a certain process window that’s consistent and reliable. And you have to have a high level of quality to ensure these tests are accurate year in and year out.”