Choosing a bottle for an IVD reagent is usually framed as a question of format: volume, neck finish and analyzer fit. The first technical question, however, is chemical: will the resin hold this formulation for its whole shelf life without changing it, and without being changed by it? A buffer that sits quietly in HDPE for two years may still lose its detergent to the wall, pick up trace extractables, or crack the bottle at the neck if the wrong grade is used.
This article summarises how common reagent components behave in HDPE, LDPE, PP and PET, with glass as a reference. The ratings are general guidance based on well-established polymer chemistry, not a substitute for testing your own formulation.
How reagents and plastics interact
Compatibility is not only about whether the bottle dissolves. Four mechanisms cause most problems in reagent packaging:
- Sorption: reagent components move into the plastic wall or adsorb onto its surface. Hydrophobic molecules, some preservatives, dyes and low-concentration proteins are typical candidates. The bottle looks fine, but the reagent loses potency.
- Permeation: small molecules diffuse through the wall. Escaping water vapour concentrates the reagent, entering oxygen can degrade sensitive components, and volatile solvents such as ethanol are slowly lost. Permeation increases with temperature and with thinner walls.
- Leaching and extractables: additives, catalyst residues, oligomers or processing aids migrate from the plastic into the reagent. Extractables are what an aggressive solvent pulls out under exaggerated conditions; leachables are what actually appears in the product during storage. Some absorb in the UV range or interfere with enzymatic and immunochemical reactions.
- Environmental stress cracking (ESC): a polyethylene part under stress (moulded-in stress, closure torque, a snap fit) cracks in contact with surface-active agents, although neither the stress nor the chemical alone would damage it. Cracks often start at the neck, base or gate and may appear weeks after filling.
Swelling, softening and discolouration are easy to see. Sorption, slow permeation and leachables are not, which is why compatibility must be judged on reagent performance as well as on the appearance of the bottle.
The resins in brief
- HDPE: the workhorse for reagent bottles. Very good resistance to aqueous solutions, acids, bases and alcohols, and a low water vapour transmission rate. Weak points are stress cracking with surfactants, swelling with hydrocarbons and oils, and relatively high oxygen permeability.
- LDPE: softer and more flexible, used for dropper and squeeze bottles. Similar chemistry to HDPE but lower crystallinity, so higher permeability and lower resistance to solvents, oils and stress cracking.
- PP: chemical resistance comparable to HDPE, generally better stress-cracking resistance, higher stiffness and, in many grades, suitability for steam sterilisation. More sensitive to strong oxidisers; homopolymer grades become brittle at low temperatures.
- PET: clear, rigid and a better oxygen and carbon dioxide barrier than polyolefins. Good with acids, dilute alcohols and oils, but hydrolysed by alkaline solutions and attacked by ketones and chlorinated solvents. Its glass transition temperature, typically around 70–80 °C depending on grade, rules out hot filling and autoclaving.
- Glass (borosilicate): the inert reference for most chemicals and solvents. It is attacked by hydrofluoric acid and, slowly, by strong alkalis, and its surface can also adsorb proteins. Weight and breakage risk limit its use on analyzers.
Compatibility by chemical class
The table summarises typical behaviour at room temperature and at the concentrations commonly found in IVD formulations, unless stated otherwise.
| Chemical class | HDPE | LDPE | PP | PET | Glass |
|---|---|---|---|---|---|
| Aqueous buffers and salt solutions (pH 4–9) | Good | Good | Good | Good | Good |
| Dilute acids and bases | Good | Good | Good | Good (acids); Limited (bases) | Good |
| Concentrated acids and bases | Good; Limited for oxidising acids | Limited | Good; Limited for oxidising acids | Not recommended | Good (acids); Limited (strong bases) |
| Alcohols (ethanol, methanol, isopropanol) | Good | Good; check weight loss | Good | Good (diluted); Limited (concentrated) | Good |
| Surfactants and detergents | Limited (stress cracking; use ESCR grade) | Limited | Good | Good | Good |
| Oxidisers (hypochlorite, hydrogen peroxide) | Good (dilute) | Limited | Limited | Limited | Good |
| Acetone, DMSO | Good; check weight loss | Limited | Good | Not recommended | Good |
| Chlorinated and aromatic solvents | Not recommended | Not recommended | Not recommended | Not recommended | Good |
| Preservatives at use level (sodium azide, ProClin) | Good | Good | Good | Good | Good |
| Oils, essential oils, fragrances | Limited | Not recommended | Limited | Good | Good |
Notes on the difficult groups
Surfactants. Triton X-100, Tween 20, SDS and similar detergents are common in clinical chemistry and immunoassay reagents. They do not dissolve polyethylene, but they are classic stress-cracking agents. The risk rises with surfactant concentration, temperature, closure torque and residual moulding stress. For detergent-containing reagents in polyethylene, specify a grade with documented stress-cracking resistance (for example tested to ASTM D1693), keep moulding stress low, and consider PP where the design allows.
Oxidisers. Hypochlorite and hydrogen peroxide slowly oxidise polyolefins, PP more readily than HDPE. Peroxide also decomposes to oxygen, which can build pressure in a sealed bottle, so vented closures and opaque containers are common choices. Dilute oxidising solutions are routinely packed in HDPE, but concentration and storage temperature should be tested.
Organic solvents. Polyolefins resist many polar solvents but absorb and transmit non-polar ones. Chlorinated and aromatic solvents swell all four plastics and belong in glass or a specially treated container. PET should not be used for ketones such as acetone. Even where a material is rated Good, volatile solvents permeate the wall, so weight loss must be measured.
Proteins and enzymes. At low concentrations, antibodies, enzymes and calibrator proteins can adsorb onto hydrophobic plastic surfaces, and glass is not immune either. This is a surface effect rather than chemical resistance, so it is not in the table. Carrier proteins such as BSA or a small amount of non-ionic surfactant usually reduce the loss; recovery should be checked at the lowest concentration in the product range.
Preservatives. Sodium azide and ProClin are compatible with common bottle resins at typical use levels. Measuring preservative content over the shelf life confirms that sorption has not pushed it below the effective level.
How to run a compatibility study
A compatibility study compares the reagent in the candidate bottle with a control, typically the same lot in glass or in the currently approved container. Fill to nominal volume, close at production torque and store upright and inverted at the intended temperature, with an additional stressed condition for early warning. EN ISO 23640 and CLSI EP25 describe how to design reagent stability studies.
| Test | What it reveals | Practical approach |
|---|---|---|
| Weight loss | Permeation of water or solvent | Weigh filled, closed bottles at each time point and trend the loss against the shelf-life specification |
| Appearance of bottle and reagent | Swelling, crazing, cracks, discolouration, haze, precipitate | Inspect against the control under consistent lighting, especially at the neck, base and gate |
| pH and conductivity | Leaching, gas exchange, degradation | Measure at each time point against the control and the release specification |
| Assay performance | Functional effect on the test | Run calibrators and controls; compare recovery, reagent blank, sensitivity and precision with the control |
| Active ingredient and preservative content | Sorption to the wall | Quantify key components, especially low-concentration ones, at the start and end of shelf life |
| Extractables and leachables | Substances migrating from the plastic | Extraction study on the bottle, then targeted screening of the aged reagent for identified compounds |
| Closure integrity | Leakage, torque loss, stress at the neck | Check removal torque and run a leak test after storage |
- Test the final combination: resin and grade, colourant, closure, liner and label adhesive.
- Include the worst case: highest surfactant or solvent concentration, highest storage temperature and the smallest bottle, which has the highest surface-to-volume ratio.
- Treat accelerated data as a screen; shelf-life claims rest on real-time results.
- Repeat the assessment when the resin grade, resin supplier or masterbatch changes.
Choosing bottles with Linden Grup
Linden Grup moulds reagent bottles in HDPE and polypropylene, including analyzer-compatible reagent bottles for common clinical chemistry systems. We can supply material information and sample bottles for your own compatibility and stability studies, and production lots are traceable under our quality system. To discuss a formulation or request samples, contact our team.