Feature Article

Advanced Pressure-Sensitive Adhesives Enable Advent of Next-Generation IVD Products


Posted in Medical Device Assembly by Brian Buntz on January 8, 2011

Conventional components for bonding, adhesives are now being formulated to deliver increased functionality and capabilities to diagnostic devices.


Pressure-sensitive adhesives (PSAs), common components found in a wide range of diagnostic devices, are evolving to be as diverse and specialised as the devices themselves. Not only are PSAs well-suited for lateral-flow devices, but high-performance bonding tapes are also used in many molecular diagnostic applications, including high-throughput screening, reverse-transcription PCR, cell culture and compound storage.

PSAs are an attractive material choice for device manufacturers because they are integral to device performance and they facilitate efficient manufacturing. They provide an immediate bond—without the use of heat that could potentially damage a device’s sensitive enzymes and reagents—in a continuous roll format that streamlines manufacturing for batch and in-line processing operations. While a number of off-the-shelf medical-grade PSA products are available, device manufacturers should consider working with a contract manufacturer specialising in adhesive formulation to develop custom products that address the unique needs of these applications. For example, polycarbonate, a material commonly used in compact disc cartridges used in centrifugal microfluidic testing platforms, is a difficult surface to bond to without proper conditioning because of outgassing1 of tiny oxygen and moisture vapour bubbles over time (Figure 2). An adhesives manufacturer with materials expertise can customise a bonding solution specifically to address this issue.
 
Inertness and compatibility
Ensuring component compatibility with the biological sample and assay is critical. This becomes even more complex when one considers the breadth and variety of available assays, and how biomarkers or reagents can be combined as device designs broaden into complex new fields of detection.
 
Medical adhesives

When considering an adhesive and the component materials for any test system, formulators must ensure the chemistry of all raw materials is—and remains—inert to the chemistries of the device and specimen. The system must be free of any residual volatiles (such as solvents) and monomers, leachable components and reactive materials to ensure the proper chemical compatibility of these materials2. Any processing components also must be considered. For example, most PSA systems are manufactured with a release liner to aid in processing. Silicone from the liner’s release coating can potentially be transferred from the adhesive to the IVD device, causing contamination that may affect growth in cell culturing applications.

While a PSA’s raw materials may, in theory, be compatible with the device components, environmental contamination can occur during the handling and manufacturing of the PSA system. Cleanliness during material handling and manufacturing is as important for maintaining compatibility as is component chemistry, particularly in molecular diagnostic applications. Any bacteria, yeast or fungi that are inadvertently transferred to test components can introduce biological contamination that may negatively affect results in biotech testing.

Compatibility can change as components age, so accelerated and real-time ageing studies are required to ensure that the adhesive properties are maintained during the shelf life of the device.

 
Thickness tolerance control
Tight tolerances for adhesive and substrate thickness control within the product rolls and from lot to lot are critical for microfluidic devices and lateral flow applications—variations in thickness can have an impact on sample volume that potentially could affect a test’s outcome. PSAs have been an important component of lateral-flow immunoassays used in many disposable IVD devices and biosensors. The precise and accurate bond lines offered by PSAs improve the reproducibility of these devices. One or more layers of a PSA tape product may be used to bond, laminate or assemble components within a test strip. For example, in microfluidic devices and biosensors, a spacer tape defines the height of the microfluidic channels, which are formed by die or laser cutting, while the lid of the channel is made of another adhesive tape or hydrophilic film3. Adhesive thickness and tight tolerances can be monitored and maintained by integrating sophisticated vision systems and state-of-the art on-line coating controls into the manufacturing equipment train to ensure product quality.
 
Eliminating cold flow
Adhesive migration, also known as cold flow, or “creep,” has always been a design challenge for adhesives manufacturers to overcome. This undesirable characteristic can result in components sticking to one another and to product packaging, or cause unwanted adhesive build-up on machinery during processing. Adhesive oozing into a test strip’s microfluidic channels can inhibit sample flow, resulting in defective product or inaccurate test results.
 
Figure 1: Microscopic view of adhesive’s pore structure.
Some trends influencing IVD devices, such as the use of smaller sample volumes and quantities of biomarkers, are driving designs that use smaller capillary channels than before. As a result, the viscoelastic properties of the adhesives used in device designs with larger sample flows may not be suitable for smaller channel designs. In these instances, a dual-stage UV-curable PSA is a good substitute. This unique construction initially functions like any other PSA for in-line processing with quick-stick properties for bonding and laminating components within an IVD device. Once assembled, the laminated construction is briefly exposed to UV light, which further cross-links the adhesive, making it more cohesive and eliminating the risk of cold flow.
 
Improving sample flow
Another way device manufacturers can reduce testing times and make use of a smaller sample volume is through the selection of an adhesive system that demonstrates hydrophilic capabilities. Hydrophilic PSA constructions serve a dual purpose in that they bond the components of the diagnostic device together while also creating a high energy surface to enhance flow of the biological fluid.4 The hydrophilic PSA may also reduce the surface tension of a fluid to allow rapid transfer of the fluid from an inlet area to a remote reagent area located in an IVD device. As a result, the rapid spreading of the fluid can reduce the time needed for analysis and enable the use of a smaller sample volume. Hydrophilic coatings and PSA systems may be used in a variety of in-vitro diagnostic devices, including capillary flow, lateral flow, microfluidic, microtitre plates and electrophoretic devices.
 
Enabling vertical flow applications
The availability of a porous PSA technology that provides the ability to bond multiple layers while enabling the free exchange of fluids or gasses is a relatively new concept.5 Originally developed by Adhesives Research for applications requiring secure containment of fluids while providing ventilation for gas exchange, such as in microtitre plates or microarrays, this technology is now being considered for IVD devices where a conventional, impermeable PSA was not previously a viable component. This customisable adhesive technology offers open pores or cells of relatively uniform size and distribution to create a low-density, highly permeable structure. The pores are isolated channels that control flow and movement of aqueous-based fluids and/or gases and they typically range in diameter from approximately 200 to 500 microns and 30% to 50% porosity. They enable flow from one substrate to the next through the z direction of the adhesive, while acting as a gasket seal in the x–y direction.6
 
Figure 2: Polycarbonate material demonstrating outgassing of oxygen bubbles and moisture vapour in a microfluidic device.
The porous adhesive’s capability to bond while allowing the free transport of fluids and gases across the two surfaces of the adhesive film may enable a number of application areas where PSAs have not been previously used in IVD devices. The adhesive forms instant bonds to join film substrates, membranes, pads, filter elements or plastic parts without the need for curing or clamping during production of the finished product. The typical pore size of 200 microns is large enough to allow the passage of a whole blood sample. Alternatively, the adhesive may be laminated to a porous membrane to filter red blood cells. For example, the porous PSA can enable the construction of a stack of filtration membranes for cost-effective sample preparation. In vertical flow or combination lateral flow IVDs, the adhesive layer can provide a physical separation between materials while enabling the rapid passage of fluids through the adhesive.7
 
Improving reagent use
As assay developers evaluate ways to reduce cost by improving assay stability and yields of expensive reagent-laden components, aqueous-based dissolvable films, a related technology to PSAs that use similar formulation and processing approaches, are gaining attention as a viable means for incorporating reagents into diagnostic devices such as lateral flow test strips, microfluidic devices and microplates. These films provide a means for containing, storing, transporting and processing reagents in a simple solid-state form. The reagents can be made available simply by re-dissolving the film in an aqueous medium. Dissolvable films can be tailored to meet the needs of a device manufacturer’s specific application and offer significant formulation flexibility for achieving the desired physical properties such as film thickness, dissolution rate, surface characteristics (texture) and mechanical properties (film strength).8
 
Figure 3: A dissolvable film can be manufactured with a fluidic pathway pattern and integrated as part of a multi-layer device.

Conventional preparation techniques for test strips such as spraying, coating or striping can result in the costly loss of reagent. These methods also can limit the even distribution of active components throughout a membrane or conjugate pad. Dissolvable films are formulated as a homogeneous mixture of a film former and reagent(s), so consistent dispersion of the active component is an inherent benefit of the film technology, translating to increased yield and reduced costs for device manufacturers.9 The film is provided in a continuous reel and may be cut into any size or shape to fit the end product design. Each precisely die-cut film component is a pre-measured, single dose that is easier and safer to handle than aqueous solutions of reagents. Higher dose concentrations can be obtained by increasing the loadings within the film itself or by increasing the film’s overall mass and thickness. Reagent-loaded dry films do not require refrigeration or preservatives. Increased stability of the reagent when it is integrated into a film format results in less waste, and requires fewer resources for device manufacturers to properly store and handle the sensitive fragile reagents (Figure 3).

 
For diagnostic applications requiring controlled timing of a reaction, dissolvable films may be incorporated as isolation barriers formulated with longer disintegration rates to delay a reaction. Alternatively, the films may be used in multiple-layer constructions and vertical flow devices that contain or separate one or more reagents for their controlled release when exposed to an analyte within a device.8
 
Conclusion
A number of influences will drive IVD device manufacturers to reduce the cost of their current products and develop innovative next-generation devices. As manufacturers manoeuvre through shortened product development cycles, they turn to their material suppliers to access the latest technologies enhancing product performance and value. The technological challenges for suppliers are many, requiring the development of efficient and reliable manufacturing processes to produce high-quality products that meet or exceed regulatory requirements. Custom adhesives manufacturers are uniquely positioned to develop and implement technologies that not only provide reliable bonding for a multitude of IVD testing platforms, but also deliver enabling technologies to address the challenges IVD manufactures are facing today, and tomorrow.
 
References
1. S.I Moon et al., “Outgassing of Oxygen from Polycarbonate,” Acs Applied Materials & Interfaces, 1, 7, 1539-43 (2009).
2. W. Meathrel et al., “Customized adhesive and coating technologies enable drug delivery methods,” Pharma, September, 20-23 (2009).
3. P. Hilfenhause et al., “Pressure-sensitive adhesive tapes for IVD applications,” IVD Technology, 16, 2, 33-38 (2010).
4. W. Meathrel et al., “Diagnostic devices for use in the assaying of biological fluids.” U.S. Patent 7476533.
5. R. Malik et al., “Porous pressure-sensitive adhesives and tapes.” U.S. Patent App. 60/978,591.
6. R. Malik, “Porous adhesive technology for diagnostic applications,” IVD Technology, 15, 2, 27-32 (2009).
7. R. Malik, “Porous Pressure-Sensitive Adhesives,” European Medical Device Technology, 1, 2, 41-43 (2010).
8. Meathrel, W. et al., “Dissolvable films and their potential in IVDs,” IVD Technology, 13, 9, 53-58 (2007).
9. W. Meathrel et al., “Disintegrable films for diagnostic devices,” U.S. Patent 7,727,466.
 
William G. Meathrel, PhD,*
is Senior Scientist
and
Ranjit Malik, PhD,
is Group Leader, Core Technology,
at Adhesives Research Inc., P.O. Box 100,
Glen Rock, PA 17327, USA
tel: +1 717 227 3460
e-mail: bmeathrel@arglobal.com
www.adhesivesresearch.com
 
* to whom all correspondence should be addressed
 


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Re:

In fact it is high time to act as per the changes that are there in the medical field. Let us have look into the changes that has occurred in the last few years.
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EMR Software
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The conventional methods of bonding have been replaced with the new and modern ones which provide fastens means of diagnosis to the patients.

The products are really good.

The products are really good. They have been on this one for quite some time. - Connie Sellecca

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Informative article.

Informative article. I am glad that there are advancements to the PSAs, and hope more improvements can be made to existing technologies. As the efficiencies for current PSAs improve, IVD products can also become more sensitive and effective, and in turn helping to save more lives.

Jenny - CPAC