Increasingly, the potential for cost savings is attracting some users to source third party tips. All too often inadequate consideration is given to whether third party manufactured tips adhere to the same quality standards as those made by the original liquid handling vendor.

Although these third party automation tips may appear to be faithful replicas of the instrument vendor tips, many end users or procurement staff have little or no awareness of the factors involved in tip manufacture (eg polypropylene resin grade; tip release agents, non-yellowing agents, manufacturing environment, etc) that contribute to a best-in-class quality tip.

It would seem illogical to use a third party tip if you must have guaranteed tip quality and best possible dispensing performance. Particularly as most vendors optimise their whole system, including the tip, to achieve the best possible performance from their liquid handling instruments.

However, there are many less demanding applications where third party tips can give excellent dispensing results and are a cost-effective option.

Competition for the automated disposable tip business is not going to disappear and if instrument vendors want to maintain their share they need to better communicate the superiority of their offering.

However, neither source of tips is immune from the advance of tipless systems, like Labcyte Echo, as acoustic droplet ejection progressively extends its capabilities to enable more aspects of mainstream automated liquid handling.

The majority of the automated liquid handling instruments available to researchers in life science and chemistry labs today utilise disposable plastic pipette tips. Tips are available in a variety of volumes, sterile, filtered, wide bore, conductive, surface treatments and racking options depending upon the instrument channel requirements and the intended application. Liquid transfers are enabled to a nd from many different types of tubes, vials, troughs, deep-well plates and microplates.

The tips used on any vendor’s liquid handler platform are invariably not compatible with or not recommended for use with a competitors instrument. A considerable investment is required in injection moulds and manufacturing facilities (Figure 1) to produce tips that conform to precise dimensions and perform repeatedl y with reliable dispensing accuracy and precision. This necessitates tip manufacture to exacting specifications under stringent quality assurance guidelines.

Disposable tips represent a significant recurrent revenue stream for the instrument manufacturer, which over the lifetime of the product frequently exceeds the purchase value of the liquid handler. Not surprisingly, the instrument vendor is anxious to recoup his investment in new instruments and associated plastic consumable injection moulds and to retain the purchasing loyalty of his customers. Recent years have, however, seen an increase in the number of third party plastic companies manufacturing and supplying disposable tips ‘compatible’ with many of the common automated liquid handlers.

Apps even exist to help guide the selection of the cor rect tip to match your application requirements in the lab. Most purchasing of third party tips is driven by price, in an environment where lab consumable budgets are very tight. Faced with increasing competition from third party plastic companies trying to ‘knock-off’ their business, liquid handler manufacturers have focused on measures which enhance the performance and quality assurance of their products (eg low retention tips, bio-certifications (particularly DNase and RNase free), traceability and extractables) and generating documentation validating the superiority of their product when used on their liquid handler.

The extent to which this had stemmed the flow is debatable as third party plastics companies attempt to play catch-up and challenge instrument vendors at their own game. Tip purchasing trends must also be viewed against other factors at play in the market. This includes tip washing, tip regeneration and the emerging use of liquid handling instruments that do not require tips, eg those based on acoustic droplet ejection.

In June 2016 HTStec In June 2016 HTStec undertook a market survey on disposable pipette tips for automated liquid handling instrumentation1. The main objective of this survey was to gain a better understanding of the dynamics associated with disposable tip usage, storage, purchase and acquisition. In particular the report attempts to define the magnitude of third party tip purchasing and what respondents feel about non-instrument vendor recommended tips. In this article highlights from the market survey are reported and the findings are discussed together with vendor updates on disposable tips used in automated liquid handlers.

Spending on disposable tips

Survey respondents allocated the biggest proportion (68%) of their automated liquid handler disposable pipette tip budget in 2016 to tips from the liquid handling instrument manufacturer. The remaining proportion (32%) of their tip budget was allocated to third party plastic companies/secondary suppliers (non-instrument manufacturer affiliated). This finding shows that third party plastic companies have already captured a significant slice of this overall market (Figure 2).

Influence of vendor statements on sourcing tips

Survey respondents were asked what attention they paid to statements by vendors such as ‘only our tips are certified for use on our instrumentation, assuring the user that every tip meets our exacting accuracy and precision requirements’. Most respondents (46%) said it makes good sense to take notice of instrument vendor statements on the use of their tips. 44% indicated they paid very little notice to instrument vendor statements on the use of their tips, with the remaining 10% paying no attention to such statements. Clearly there is a degree of scepticism among respondents that only instrument vendor tips are best (Figure 3).

Main drivers for consideration of third party tips

‘Instrument vendor tip pricing is too high’ was ranked the greatest influence in driving survey respondents to find alternative third party ‘compatible’ disposable pipette tips. This followed in the rankings by internal drive to reduce costs, search for higher quality product, and then cutbacks in consumable budget. Ranked least influence was issues with tip packaging/racking (eg desire to reduce static build-up and deck space utilisation) (Figure 4).

Main influence on purchasing third party tips

Cost was rated by survey respondents as the main influence on a decision to purchase specific third party ‘compatible’ disposable pipette tips. This was followed by in-house dispensing accuracy and precision assessment, and then availability and optimised geometry for use with specific automated liquid handlers. Rated least influence was packaging/ racking options available (Figure 5).

Do third party tips compromise quality?

The majority (67%) of survey respondents felt that using third party ‘compatible’ disposable pipette tips would compromise to some extent the quality of their pipetting. It was followed by 23% who believed it would have no effect, with the remaining 13% feeling it would compromise the quality of their pipetting (ie fail to meet respondents’ accuracy and precision requirements), which is why they prefer not to utilise them (Figure 6).

Experience of using third party tips

Most (48%) survey respondents’ experience of third party ‘compatible’ disposable tips was adequate (ie, some limitations but useful for most applications). This was followed by N/A (ie not used third party tips) (19% responding); and then very positive (ie have proved an excellent buy, use routinely and would recommend to others) or negative (ie had to revert to instrument vendor tips) (both with 17% responding) (Figure 7).

Reuse of disposable tips

One of the easiest ways to reduce disposable tip costs is to reuse them. It is therefore of interest that the majority (66%) of survey respondents never reuse disposable tips, ie use for one liquid handling step only, then discard. The remaining 36% reuse disposable tips within the same protocol or reuse of disposable tips for completely different protocols or applications after washing.  No respondents reported reuse of disposable tips for completely different protocols or applications after washing (Figure 8).

Regeneration of used tips

Another approach to reduce disposable tip costs and minimise plastic waste is to use a tip regeneration method. One such method is IonField Systems TipCharger IonPlasma tip regeneration that uses rapid ionisation and liquid-to-gas conversion to clean and decontaminate pipette tips for immediate re-use. Investigation of the use of tip regeneration methods, to reduce disposable tip costs, showed that the majority (72%) of survey respondents have not considered this approach. A further 19% of respondents have not used tip regeneration methods but are considering using in the future. In addition, 6% of respondents are not using tip regeneration and have concerns that ion bombardment contributes to changes in pipetting performance. That left only 2% of respondents that have already deployed tip regeneration methods (Figure 9).

Quality bio-certifications

Increasingly end-users are demanding tips that have been independently tested and certified to be free from potential contaminants that may negatively impact assays. Of a list of known quality biocertifications or features of disposable tips available on the market, the majority (69%) of survey respondents chose sterility. This was followed by DNase-free (64% needing), RNase-free (58% needing) and then DNA-free, human (49% needing). Least needed was ATP-free (Figure 10).

Extractables from plastic consumables

Chemical substances leaching out of plastic consumables (referred to as extractables or leachables) are frequently underestimated in the majority of life science applications. However, increasing scientific evidence shows that this heterogeneous group of chemicals may significantly affect experiments using disposable pipette tips and pose a likely source of error in various assay systems. Extractables have also been implicated in causing cellular toxicity, carcinogenicity and decreased stability over the shelf life of a product. To try and understand how extractables are viewed we asked survey respondents if they considered them. The results showed that most (96%) of respondents do not evaluate and verify the effect of extractables from automation consumables on assay performance and sample storage efficacy. This response was equally split between those that have not considered extractables and those that were happy with the assurances given by the tip manufacturer with respect to possible extractables. This left only 4% of all respondents that have currently investigated extractables (Figure 11). It is worth stating here that while leachables can be attributed to pipette tips, the residency time of the sample in a pipette tip compared to its time in the reaction or storage plate is very small. Assay inhibition issues have been associated with the labware used for storage or the assay plates themselves; since in many cases the plates are temperature cycled (eg for PCR) which releases low molecular weight polymer additives.

Low retention tips

Low retention tips are a relatively new innovative feature added by some vendors to differentiate their disposable pipette tips. Low retention tips utilise a surface treatment to make the polypropylene of the pipette tips extremely liquid repellent (hydrophobic), reducing sample loss during pipetting, which some claim will enhance pipetting accuracy and yield better quality data. Most (50%) survey respondents placed moderate value (ie sounds useful and worth evaluating) on ‘so-called’ low retention tips. This was followed by 25% placing high value (ie we have shown them to be worth the extra cost), 18% placing no value (ie would not purchase), and the remaining 7% who have concerns (ie repellent surfaces or coatings contribute to extractables) (Figure 12).

Traceability

Traceability is another term that pipette tip users may have encountered. Lot-numbered tip packages and individual tip racks are now the norm, but what difference does it make to end-users? The survey found that most (45%) respondents placed no importance on pipette tips being guaranteed fully traceable from mould to the bench (ie cannot think of an occasion where they have or would use this information). A further 36% think it moderately important that pipette tips are traceable. That left 19% who think tip traceability is critically important (ie a must-have for potential quality assurance issues) (Figure 13).

Alternatives to tip-based liquid handling

Another liquid handling technology that has gained considerable traction in recent years is acoustic droplet ejection which does not utilise pipette tips (eg Labcyte Echo or EDC Biosystems ATS). One of the main selling points of this approach has been that it reduces operating costs by eliminating disposable tips and reducing waste generation. This led us to investigate in the survey whether the ongoing cost of pipette tips had resulted in any respondents contemplating the purchase of an acoustic liquid handler. Opinion was relatively evenly split between the question options available. 44% answered Yes – this was divided between 23% that have deployed acoustic dispensing and 21% who are considering acoustic dispensing. 32% answered No – this was divided between 19% reporting acoustic systems are not suited to their liquid handling applications and 13% reporting that the cost of acquiring acoustic systems is prohibitive. That left 23% who answered N/A – do not know enough about acoustic dispensing to comment (Figure 14).

Latest developments in disposable pipette tips

The following vendor snapshots describe some of the latest developments in disposable pipette tips.

Agilent (www.agilent.com) currently offers a variety of pipette tips designed and validated for the Bravo Liquid Handling Platform that cover a wide range of pipette volumes from 0.3μL to 250μL. This includes 10μL, 30μL, 70μL and 250μL pipette tips for the 96LT, 96ST or 384ST Bravo heads. Agilent’s pipette tips also come in a wide range of configurations (sterile, filtered, wide bore, conductive and multiple types of nested racks) to meet a variety of experimental needs and workflow optimisation. Agilent pipette tips are manufactured in a tightly-controlled environment (ISO 9001 and ISO 11137, registered and audited) and are subjected to rigorous testing procedures to meet performance standards. This includes performing the following QC tests: free of DNase/RNase activity, free of endotoxin contamination, free of human DNA, free of protease activity and free of heavy metals. Agilent recently upgraded its sterilisation methods so that each pipette tip is sterilised with a dose range of 12-35 kGy to a sterility assurance level of 10-6. This close range is audited through quarterly bioburden and sterility validation studies performed to ANSI/AAMI/ISO 11127 standards (Figure 15).

Alpha Laboratories (www.alphalabs.co.uk) supplies an extensive range of robotic tips for a wide variety of automated workstations. Increasingly, laboratories are moving towards automation as improved accuracy and precision are becoming progressively more important, alongside higher efficiency in liquid handling applications. Manual liquid handling requires a high level of experience and a perfected technique for good reproducibility. Even then, variation between users applying the same technique will affect consistency of results. Automation eliminates variation based on user experience and technique as well as significantly reducing the amount of time required to perform both simple and complex tasks. For an experienced user, filling a 96-well plate can take around a minute with a multichannel manual pipette, 30 seconds with the multi-dispensing function on an electronic pipette, but less than five seconds on an automated platform. The individual design and calibration of Alpha Laboratories’ robotic tips ensures perfect instrument compatibility for the most accurate results. Both conductive and non-conductive robotic tips are available for different appli cations. The non-conductive tips are manufactured from clear medical-grade polypropylene. The conductive tips are manufactured using a composite of conductive carbon black and polypropylene which carries liquid- sensing properties. The tip filling height is automatically recognised guaranteeing minimal tip immersion and reducing liquid carryover. All the tips are manufactured under ISO 14644-1 compliant class 8 clean room conditions. They are packaged in workstation-compatible racks and inserts that require minimal handling, thus safeguarding sample integrity. Furthermore, independent laboratories are used to certify each lot of tips contamination- free (Figure 16).

The design goal of CyBio® liquid handling instruments from Analytik Jena (www.analytikjena. com) is to provide the best possible pipetting results. Since pipetting tips are an integral part of any liquid handling system, Analytik Jena pays great attention to their design as well as their interaction with the instrument. Analytik Jena believes both instruments and pipetting tips should be sourced from the same manufacturer so users can benefit from the highest precision and repeatability of dispensing. With its latest introduction, the CyBio® RoboTipTray, it continues to increase the degree of liquid handling automation. CyBio® RoboTipTrays are automatically loaded by the pipetting head from the instrument deck. Rigid racking of the tips in the CyBio® RoboTipTrays provides uniform distance and tip end height in relation to each other as well as to the pipetting head. Analytik Jena’s unique Tip Sealing Technology – sealing each tip head’s flange against an elastomer mat – is the basis for high precision and repeatability. Centring pins guarantee exact positioning of the complete set of tips to the pipetting head and thus to the labware. This reliably enables liquid transfers especially of low volumes and when using labware with small well diameters including 1536-well microplates. Additionally the centring pins are utilised to nest the CyBio® RoboTipTrays. They can be stored compactly, and they can be transferred between storage and liquid handling instruments by a robotic gripper, both enabling a higher level of integration of pipetting tip usage into workflows run on laboratory automation systems (Figure 17).

Beckman Coulter’s (www.beckman.com) Biomek® pipette tips are the only ones validated and approved for use with Biomek workstations; seamlessly integrated into Biomek software. Tip definitions, pipetting techniques and templates and colour-coded tip racks are built into Biomek software to make set-up, method writing and operation efficient and convenient. As a crucial component to the most advanced liquid handling systems, Biomek pipette tips are certified to be free of RNase, DNase, DNA (human and mouse)/PCR® inhibition, endotoxin and trace metals. In addition, only premium-grades of virgin polypropylene are used to provide chemical resistance and minimise any potential for leachable components. Non-conductive tips offer the advantage of being clear (versus black) to allow for visual inspection of aspirated volumes and the uniformity of aspirated volume across tips. Black, conductive pipette tips offer the advantage of enabling liquid level sensing of pipetted matrices in labware and to track the volume of liquid as it is aspirated from (or dispensed to) the labware via Biomek software. Biomek Wide Bore tips are non-conductive tips which are designed with a pipetting orifice twice the size, eg 1.4 mm, of standard pipette tips to reduce shearing of samples. Through the use of Computational Fluid Dynamics (CFD) software, physical forces and flow characteristics within a pipette tip during pipetting can be simulated. Comparisons of pipette tip orifice diameters are analysed for such parameters as fluid (sample) velocity and shear strain rate. Less fluid velocity, wall shear effects and shear strain rates are desirable in preserving the biological integrity of native samples during sample preparation (Figure 18). Loss of biological sample integrity can occur when pipetting fragile cell suspensions, hybridomas, embryoid bodies or spheroids, algal coagulates, protein aggregates and genomic materials due to the pipette tips’ small internal orifice diameter and the speed of aspiration and dispense during pipetting. Additionally, sample preparation times can be reduced with faster pipetting speeds of viscous reagents, such as glycerol stocks or bead mixtures.

Biotix® (www.biotix.com) offers automation tips that are compatible with multiple platforms including Agilent, Beckman, Molecular Devices and Hamilton. The process of creating its aTIP™ Pipette Tips starts with massive amounts of research into current complications with the market such as static, inconsistent draws, tip fitting, low CV values, accuracy and many more. Once the problems have been identified Biotix takes a generic tip and outfits it with different innovations discovered by its team of engineers to make A Better Tip®. For example, static is a large issue in 384 format tips and could cause a robot failure. Biotix solved this issue by introducing Statix®, which uses a copper button and conductive pad which in unison uses your body’s natural charge to release static in the tips. A secure seal between the tip and platform is very important when talking about robot error and CV values. Biotix outfits its automation tips with FlexFit® technology which allows it to fit most automation heads securely across multiple platforms. In 2017, Biotix will introduce the first 384 reload allowing for space saving and reduced plastic waste. Biotix claims it is not just making another tip that fits an automation platform, it is pushing the design of the tips and creating the future for other companies to follow suit. This helps to allow researchers to get more accurate results, work with lower volumes and help push laboratory capabilities to the next level (Figure 19).

The fact that a tip fits on to the cone of an automation dispensing tool does not say anything about the performance of the automated pipetting system. Such pipetting systems are made up of hardware components, pipette or dispensing head, the tip consumable and the software components. During development, Eppendorf (www.eppendorf. de) optimises the whole system carefully for the best possible performance for all its liquid handling instruments. The standard ISO 8655:2002 (1) recommends using pipette and tips from the same supplier. The same is true for the ISO IWA 15 which describes the determination of performance of automated liquid handling systems. Eppendorf, as a system provider, manufactures a whole system and not just single parts. Eppendorf claims to have a natural interest in observing tight production tolerances regardless of batch and can therefore ensure high tip quality from tip to tip for its customers. For the new epMotion small volume system for dispensing volumes down to 200nL, it achieved a high performance at 1μL of <3 % accuracy and <3% precision (non-contact) only because all parts of the new system (dispensing tool, tips and software) have been optimised to each other. Eppendorf is known for its premium quality of consumables. To ensure the best possible performance of its automated liquid handling systems it manufactures tips in various qualities (including PCR clean with filter, sterile, sterile and filter), in four different sizes and in different packaging (as reloads, in racks and in SafeRacks) (Figure 20).

In drug discovery, proven products and technologies are critical for researchers, especially when working with precious compounds in limited supply. Even a seemingly small risk can result in significant delays, unexpected costs or, worse, loss of sample. In automated pipetting workflows, risking an unproven tip during pipetting steps could result in sample loss or contamination, or pipetting errors. Hamilton Robotics (www.hamiltoncompany. com) pipette tips alleviate this unwanted risk via patented CO-RE® technology. Here, a circular groove on the tip’s interior precisely corresponds to an O-ring on the pipetting channel. Together, they form an air-tight seal with precise, lock-and-key alignment to ensure the highest dispensing precision without risk of cross-contamination. Unlike other tip configurations that may deform during forceful mechani cal mounting and cause dispensing irregularities, dropped tips or introduce aerosols during forceful tip ejection, the CO-RE tip’s unique design does not require any vertical force to mount or eject the tip. Hamilton says it is not just a proven tip technology that provides peace of mind to users, but with it is its commitment to meticulous manufacturing and quality processes, as evidenced by its ISO certified facilities. Researchers value predictability and reliability; so day-to-day, lot-to-lot, and year upon year, Hamilton makes sure that its tips are absolutely identical. Additionally, all Hamilton platforms include tip type detection, automatically detecting the size of tip loaded, and TADM (total air displacement monitoring) allowing users to monitor every aspiration and dispense, to further increase process security when using CORE tips (Figure 21).

Many of the shortcomings and challenges of tipbased liquid handling can be avoided altogether by using a tipless system such as the Labcyte® (www.labcyte.com) Echo® liquid handler. These robots use acoustic liquid handling technology and are completely touchless – no tips or nozzles – so no material contacts the sample on its journey from source to destination. There is no risk of sample contamination or reagent carryover, plastic leachables from the pipette or non-specific binding of sample. Pipette tip costs and waste are fully eliminated. Unlike tip-based systems, the high accuracy and performance of Echo liquid handlers are independent of volume transferred. With this technology, sound waves eject precisely-sized droplets from a source microplate to an inverted destination microplate suspended above it. Accurate, precise transfer is possible at volumes as low as 2.5nL, while higher volumes can be achieved by ejecting hundreds of 2.5nL droplets per second. Droplets of 25nL can also be transferred rapidly to build volumes faster. The miniaturisation possible with Echo liquid handlers saves reagent costs, reduces sample consumption and waste and increases throughput. They dispense a wide range of fluid types, including DMSO and aqueous-based solutions, without requiring users to perform any calibration. The Echo system easily integrates into robotic systems for walk-away processing and can transfer liquids from any well to any well for rapid cherry picking and complex assay assembly. The Echo liquid handler is ideal for high-throughput applications including compound management, primary and secondary screening, assay development, genomics and personalised medicine. By eliminating the significant issues associated with traditional tip-based methods, this platform has enabled the discovery of new therapeutics, improved diagnostics and better selection of medicines for targeted, patient-specific treatments (Figure 22).

PerkinElmer (www.perkinelmer.com) offers a portfolio of Robotic Certified Tips specifically engineered with the highest degree of uniformity; thus, providing unparalleled accuracy in processing high-density microplates for high-throughput applications. The disposable tips are made from medical grade 100% virgin polypropylene, manufactured in a clean room environment to eliminate contamination, tested to be nuclease- and pyrogenfree, and inspected with strict tolerances for straightness, uniformity and performance. PerkinElmer delivers a wide volume range of disposable tips available without compromise. The dynamic portfolio offers clear, conductive, sterile and filter tips supporting volume transfers from 0.5ul to 5ml. Combined with the patented Accusense™ liquid level-sensing technology available on the JANUS G3 portfolio of automated workstations, the conductive tips offer detection of ionic and non-ionic liquids and ensures optimal pipetting performance without unnecessary external contamination of the tips. The high-throughput Robotic Certified Tip family ensures optimal pipetting performance with features like a direct fit seal that eliminates the need for unnecessary O-rings. Direct-fit seals improve dispense accuracy and reduce maintenance, such as the replacement or lubrication of seals. PerkinElmer offers an extensive quality portfolio of tips to meet the demands of high-throughput applications and performance requirements (Figure 23).

Tecan (www.tecan.com) pipette tips are tailored to customer application requirements on Tecan liquid handling automation systems. Recently, Tecan introduced nested MultiChannel Arm™ 96 (MCA96) and Liquid Handling Arm™ (LiHA) 350μl disposable tips for high throughput labs for increased on-deck tip capacity and walk-away time. To address the need for dispensing small, sub microlitre volumes accurately and reproducibly, Tecan has developed 10μl LiHA tips. These tips provide a huge benefit for applications requiring low volume pipetting because of factors such as high assay sensitivity, cost of the reagent and scarcity of the sample. Further, the 10μl LiHA tips are also available in the nested format together with filters for customers wanting to take advantage of both stackable and filtered tips for their specific application. The performance of an entire automated liquid handling system is dependent on every aspect; right down to each individual pipette tip. As Tecan tips are developed together with Tecan instruments, the instrument qualification/ operation qualification (IQ/OQ) is always performed only with Tecan tips to assure that every pipetting step is reproducible. With pipette tips that are designed specifically for Tecan liquid handling systems, Tecan empowers laboratories to automate their assays and be assured that every test is performed correctly (Figure 24).

ThermoFisher Scientific (https://www.thermofisher. com/search/browse/results?customGroup=Cons umables+for+Automated+Applications) is the world leader in serving science with products covering nearly every part of laboratory workflows, enabling customers with essential products from labware to complex analytical equipment to pipette tips. Along with decades of manufacturing and commercial experience for both manual and automation pipette tips, ThermoFisher also brings added expertise and knowledge of how the automation tip and automated liquid handler can help to optimise automation in the lab. It has technical knowledge to support customers when converting to ThermoScientific™ automation tips. The portfolio includes not just automation tips for most automated liquid handlers, but also ThermoScientific ™ D.A.R.T.s™ automation tips for the Thermo Scientific™ Versette™ automated liquid handler. ThermoScientific MSIA D.A.R.T.s are tips containing microcolumn technology that enable protein purification within a disposable automation tip, compared to traditional beadbased methods. MSIA microcolumns are available for both the Versette and Tecan™ MCA platforms. In addition to the broad portfolio of automation tips for many of the most popular automated liquid handling platforms, ThermoFisher also offers distinctive tips. These include wide bore, low retention and extended length tips that can be used for a wide variety of of specific customer applications (Figure 25).

TTP Labtech (www.ttplattech.com) has developed its own unique range of disposable pipette tips that can be used with its automated, low-volume liquid handling range particularly in areas such as genomics or protein crystallography. These tips use positive-displacement technology for aspirating and dispensing volumes as low as 25nL, which is not possible for pipette tips using air-displacement pipetting. In the case of the low-volume mosquito® range of instruments (single, 8- or 16-channel volume range 25-1,200nL), each micropipette tip has its own individual piston that is in direct contact with the liquid. With no air gap, the aspiration and dispense force remains constant enabling even the most viscous samples to be pipetted accurately and precisely with negligible dead volume and no crosscontamination. TTP Labtech’s tips are stored in unique high-density spools of up to 36,000 tips (Figure 1) and are manufactured on site. Its inhouse tips undergo 100% QC whereby the physical parameters of each tip are checked via imaging. Unlike most standard tips, TTP Labtech provides guaranteed performance for the tips in combination with its instruments. The success of TTP Labtech’s novel positive-displacement technology has led to the development of liquid handlers that pipette larger volumes: mosquito® HV, 0.5-5μL and dragonfly®, 0.5μL-4mL. dragonfly’s disposable tips have been designed to provide non-contact independent channel dispensing of any volume, of any liquid, into any well, with no crosscontamination (Figure 26).

Discussions

There seems little doubt that nearly all types of disposable pipette tips could be cloned by a third party plastics manufacturer today. Given sufficient investment there is no reason why third party ‘compatible’ tips cannot be moulded to adhere to the same strict dimensional tolerances or design features as the original automated liquid handling vendors’ tips. What potential purchasers tempted by primarily a cost saving of a few cents per rack need to consider is do all third party manufactured tips adhere to the same quality standards as those made by the original liquid handling vendor. It is perhaps all too easy to conclude based on previous experience with hand-held pipettors that a tip is a tip whatever the intended use. However, the potential impact of unreliable pipetting is much greater when using a multi-channel head on an automated liquid handler and large amounts of assay data may have to be trashed if a tip head crashes, a pipette tip is missed or if there was unexplained cell toxicity.

When selecting an automation tip end users need to be aware of the factors involved in manufacture that can ultimately contribute to their quality. Of importance here are the following:

1) Polypropylene resin grade. Does the resin used meet USP Class VI and/or ISO 10993 guidelines for medical devices? These resins typically contain less (if any) additives, which can be extracted (or leached) from the polymer structure. Do tip manufacturers conduct mass spec analyses on resins prior to their selection, or just assume virgin polypropylene is 100% pure?

2) Tip release agents. Does the manufacture involve the use of any release agents or additives to the ease tips off the mould? Such agents may have unknown toxicity in bioassays. A skilled injection moulding shop relies on years of product and tool design expertise so as not to use any release agents.

3) Non-yellowing agents. These are added to minimise (or slow) the yellowing of the polypropylene post-irradiation sterilisation. An alternative is to sterilise tips with ethylene oxide gas, a process which is less likely to induce tip yellowing. In addition ethylene oxide sterilisation has been shown to be superior to radiation, especially when working with nucleic acids.

4) Manufacturing environment. Is it tightly controlled and does it comply with ISO clean room conditions? Most end-users do not think, or are unaware, of these types of risk issues when purchasing or specifying pipette tips. This is particularly the case where procurement gets involved and makes the final decision on tip supplier and not the end-users who have to live with the results of poor dispensing and flawed assays and data.

Most vendors optimise their whole dispensing system, including the tip, to achieve the best possible performance from their liquid handling instruments. Third party manufacturers do not have the same motivation to improve a liquid handler’s performance or to continually extend its dispensing capabilities, and rarely is their familiarity with an instrument comparable to liquid handling vendors. By undermining the liquid handling vendors business, purchasers of third party tips are indirectly contributing to make the liquid handling robot they purchased less competitive or cutting edge.

Like many things in life, you get what you pay for. If you must have guaranteed tip quality and best-possible dispensing performance, it would seem illogical to purchase third party tips. However, there are many less stringent applications where third party tips give excellent dispensing results and are a cost-effective option. Competition for the automated disposable tip business is not going to disappear and if instrument vendors want to maintain their share they need to better communicate the superiority of their offering. However, neither source of tips is immune for the advance of tipless systems, such as Labcyte Echo, as it progressively extends its capabilities to enable more aspects of mainstream automated dispensing. DDW

Dr John Comley is Managing Director of HTStec Limited, an independent market research consultancy whose focus is on assisting clients delivering novel enabling platform technologies (liquid handling, laboratory automation, detection instrumentation; assay methodologies and reagent offerings) to drug discovery and the life sciences. Since its formation 15 years ago, HTStec has published 128 market reports on enabling technologies and Dr Comley has authored 59 review articles in Drug Discovery World. Please contact info@htstec.com for more information about HTStec reports.

References

1 Disposable Tips For Automated Liquid Handlers Trends 2016. Published by HTStec Limited, Godalming, UK, June 2016.

2 Lund, Robert D (2017). Analysing the Effect of Pipette Tip Geometries on Fluid Velocity and Shear Strain Rate: Biomek Wide Bore vs Standard Pipette Tips. Tech Info Bulletin. Beckman Coulter Life Sciences, Indianapolis, Indiana, USA.