Once a test-strip matrix has been established, it is then necessary to optimize it and develop the requisite protocols for its efficient and cost-effective manufacture. This discussion will focus only on the mechanical design of the test strip and not on the chemistry or the mechanics of the test itself.
It is necessary to first understand the manufacturing process as it relates to materials and tolerances. Each component of the test, including membrane, backing substrate, and each of the pad materials, has a defined dimension and an associated dimensional tolerance. For example, assume a membrane with a nominal width of 25 mm. The membrane has a manufacturing tolerance associated with it. Depending on the process utilized to produce the membrane, this tolerance could be as low as ±0.10 mm to as much as ±1.00 mm. In the former case this means that the material can be between 24.90 mm and 25.10 mm wide and still be within its specified tolerance range. In the latter case, the material can have an allowable width between 24.00 mm and 26.00 mm. There is a big difference between these two sets of dimensions.
The lamination process for test strips involves the layering of the materials in such a way as to produce defined interfaces between components. It may be necessary that the conjugate pad overlap the nitrocellulose membrane, for example, by a defined amount of 1 mm. Depending on the tolerances of the materials and the means by which they are laid down in the lamination process, this overlap could, in fact, end up as a gap.
Tolerances play an important role in the function of the end product, and it is critical that their role be well understood. If material tolerances are specified too tightly, then material costs will be high. If process tolerances are specified too tightly, then yields will be low and manufacturing equipment costs will be high. If material and process tolerances are specified too loosely, then the product may not function as desired. It is important, therefore, to strike a balance in the specifications of both the material and process tolerances. It is also important, in the process, to discuss tolerances with materials suppliers and determine what tolerances can be held and the costs associated with those tolerances. There are trade-offs associated with these decisions. Tighter material tolerances generally allow somewhat looser manufacturing tolerances. Looser manufacturing tolerances allow higher yields, lower equipment costs, and lower product costs. It is probably safe to say that most tolerances for web materials will fall in the range of ±0.1 mm if they are produced from hard tooling, to ±0.25 mm to as much as ±1.00 mm if from adjustable tooling. It is usually best to hold material tolerances as tight as is practical and cost effective, as this will allow higher yields from the lamination process.
As mentioned previously, the lamination process will provide defined overlaps of the materials generating a flow path for the test fluid. In defining the dimensional and tolerance requirements for this process, it is critical to understand that all of the dimensioning and tolerancing must be established from a single reference or datum edge. This reference datum is typically one edge of the backing substrate. Regardless of whether the product is being laminated in a continuous web process or in discrete sheets, one edge of the substrate material should always be considered the datum reference point. Lamination dimensions should not be defined between the different layers of
the laminate; they should be defined from the reference edge of the substrate. As illustrated in Fig. 1, the left end (position A) would be considered the datum edge, or datum 0.
Every material has dimensional tolerances. Every process has dimensional tolerances. It is important to understand these tolerances and their interrelationship. A thorough understanding of dimensioning and tolerancing will help avoid some very common pitfalls in the design of lateral-flow assays.
Referring to Fig. 1, the following assumptions are made regarding the materials:
Material Sample pad Conjugate pad Membrane Absorbent pad Plastic backing
Dimension 12 mm 8 mm 25 mm 12 mm 49 mm
Tolerance ± 0.25 mm ± 0.25 mm ± 0.25 mm ± 0.25 mm ± 0.25 mm
Dimensional range 11.75 mm to 12.25 mm 7.75 mm to 8.25 mm 24.75 mm to 25.25 mm 11.75 mm to 12.25 mm 48.75 mm to 49.25 mm
It is further assumed that the equipment accuracy for the placement of each of the materials is ±0.25 mm. This is the process tolerance. In this example, A is considered the 0 reference point, or "0 datum." This is the edge of the plastic backing material. Because this is the primary element in the assembly of the laminate, it must always be the starting point for dimensioning the locations of the other materials.
In most typical lateral-flow assays, the sample pad is intended to be coincident with the edge of the plastic backing material. This means that its left edge would be coincident with datum 0. Because this has a process tolerance of ±0.25 mm, the left edge of the sample pad is truly at a position from -0.25 mm to +0.25 mm. Its right edge (C) is at a nominal dimension of 12 mm ± 0.25 mm. However, considering that the left edge is at 0 ± 0.25 mm, C therefore is actually at 12 mm ± 0.50 mm (the sum of the two ±0.25 mm tolerances).
In the next step, the specified overlap of the sample pad over the conjugate pad (B - C) is defined to be 6 mm ± 0.25 mm. This is not possible because position C is only accurate to within ±0.50 mm, and because the accuracy of the equipment to place the edge of the material is only ±0.25 mm, the overlap can only be within ±0.75 mm if the conjugate pad is placed with respect to its left edge (B). The overlap tolerance would be ±1.0 mm if the equipment were referencing the right edge (E) of the conjugate pad because its material tolerance (±0.25 mm) must also be taken into consideration.
Next, if a 1-mm overlap of the conjugate pad onto the membrane is desired, depending on the edge from which the previous two materials are referenced as they are laminated, the location of E is known only to within ±0.75 or ±1.0 mm. If the edge (D) of the membrane is used for registration (tolerance of ±0.25 mm), then its location is within ±1.0 or 1.25 mm of nominal. This means that there could be as much as 2.25 mm overlap (1 mm defined dimension plus 1.25 mm total positional tolerance), or there could actually be a 0.25 mm gap between materials (1 mm defined overlap dimension minus 1 . 25 mm tolerance).
Obviously, the sample pad, the conjugate pad, and the membrane are not laminated in the order described above, as the membrane must be placed first so that the other materials can be made to overlap. But this illustrates the close attention to the tolerances required when dimensioning the product.
The proper way to dimension the lamination is to first determine the most important relationship. Keep in mind that one edge of the plastic substrate material must always be the primary reference point (datum 0). If the most important relationship is a 1.0-mm overlap of the conjugate pad over the membrane, then relative to datum 0, the equipment must register the edges of the material that define this dimension—D for the membrane and E for the conjugate pad. One can then determine the dimensional relationships of the other materials accordingly, making sure to reference each of the other dimensions from the datum edge of the backing material. If the next most important relationship is the overlap of the absorbent over the membrane, then define the location of the absorbent (F) relative to datum 0 (A). The location of G can be determined only by adding the dimensions D plus its process tolerance (±0.25 mm) and the nominal width of the membrane (25 mm) plus its mater-
ial tolerance (±0.25 mm). Refer to Fig. 2 for examples of proper and improper dimensioning of the laminate.
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