|LABORATORY AUTOMATION SPECIALISTS|
Robotic Sample Processors
The Beeline SX sample processors are the latest in HTZ's well established range of automated liquid handling instruments. Incorporating high-speed stepper motor drives, and the latest sample barcode reading technology, the Beeline SX range provides high-throughput processing for all sample pipetting tasks and many other liquid handling applications
The Beeline SX is an automated liquid handler designed specifically for pipetting samples with maximum precision, accuracy and security. It comprises an XYZ mechanism to move one or more pipetting probes around the Deck of the instrument to perform tasks such as sample pipetting, sample dilution and reagent addition. It is an inherently flexible system designed to pipette from any source tube or container to any target vessel, all under the control of easy to use software.
Key Beeline SX features:
Excellent pipetting accuracy and precision throughout a wide volume range (1µl upwards)
Applications Software caters for just about any pipetting task
Accepts any rack or container (provided that it holds containers securely and reproducibly)
Automatically reads sample and target barcodes for totally secure processing
Comprehensive interfacing options for both import and export of sample associated data
Comprehensive recording of processing information
Robust and reliable technology used throughout
The Beeline range of automated liquid handlers has been developed over many years and has evolved to incorporate the latest developments in robotics and software technologies to maximise reliability and performance. The SX designation marked the introduction of the very latest series of mechanics and electronics and represents a significant jump in performance of the Beeline range over previous models, especially with regard to processing speed and throughput. The Beeline SX range accepts a large number of accessories making it suitable for clinical, industrial and pharmaceutical procedures. The Deck can be populated with a variety of racks and accessories depending on the requirements of the specific application being automated. Essentially, the Deck is "open" and will accommodate just about any item that can be fitted within the confines of its working envelope.
Other Beeline SX features include:
Fully customisable and readily optimised for each application
Two Deck Size options
Capacitive, pressure or conductive liquid level detection
High-resolution, high-speed syringe drives
Fixed Needle Probes (eg fluid filled) or Disposable Tip (air displacement)
1 Probe or 2 Probe configuration options
Variety of Applications Software control options to cater for just about any pipetting task
When it comes to choosing an automated liquid handler, the starting point is always to consider the pipetting task that you want to perform. Significant considerations which will affect your choice of automation include the following:
Processing speed required eg number of samples per hour
We aim to provide some basic information here to help you decide whether a Beeline SX is suitable for your laboratory workflow. However, please contact your HTZ distributor to discuss any requirements in detail before making a decision.
The Beeline SX range includes two standard models with different deck sizes, the Beeline 300 SX and the Beeline 500 SX. Other sizes are available for customised systems. Other than the physical deck capacity, each instrument offers the same range of accessories and options.
Rack Location System
The deck itself is made from a chemically inert, high-pressure laminate casting very similar to that used for laboratory benchware. The basic rack location system comprises a narrow locating "rail" fixed to the deck along the length of the instrument at the back and front. Special adjustable locating "pegs" are fixed on these rails and racks are located on top of these. Where existing lab racks need to be used, customised adaptor plates are provided which also locate on these pegs. This simple system allows all racks to be located, reproducibly, anywhere on the deck and keeps the deck itself easy to clean. The racks remain easily removable for loading convenience or for cold storage purposes.
For other items, such as the Slide-In-Rack barcode reading module or accessories such as the microplate incubators, one or more fixing points are provided on the deck itself.
The black rack locating rail and rack locators are visible at the front of the Deck illustrating how the racks are located.
Customised rack options
Whilst HTZ has a comprehensive range of racks available, it is sometimes beneficial to provide custom racks to make the most of the available deck. Most of our racks are made from stainless steel and metal pillars except for some of the very largest racks where heavy gauge aluminium is used to save weight. The base of the racks incorporates at least two locating holes to engage with the rack locator pegs described above.
Combination disposable tip and microplate rack
A "Layout" refers to the combination of racks and other devices which sit on the deck and which need to be processed by the pipetting probes. With bench space being at a premium, it is important to optimise the deck to suit individual laboratory requirements. Prior to purchase, we determine the full requirements of your application and will design a Layout to let you know what is possible using standard HTZ or user racks or a combination of both. Sometimes, we may recommend a custom rack if significant gains in capacity or convenience can be achieved. For example, in some situations, customised racks can help avoid unnecessary transfer of tubes from one rack to another or even decanting of liquids from one bottle to another.
A key factor affecting the Layout and the capacity of either system will be whether samples and target consumables such as microplates or microplate strips will be barcoded. If they are, then there is a choice of barcode reading technologies available to choose from. See below for further details.
For many labs, a single Layout is sufficient to accommodate all the work that will ever be perfomed by the machine. However, in some cases, it may be more convenient or necessary to have multiple Layouts. For example, one application may require samples to be pipetted into the maximum possible number of microplates that can be fitted on the deck and another may require that samples are pipetted and diluted into a set of 5ml tubes. It is therefore desirable to be able to easily swap between the two different Layouts which, given that most or all of the racks are readily removable, is easily achieved.
Associated with the different physical Layout is a software definition of the Layout. This "describes" to the machine exactly where the racks are located on the Deck in terms of X, Y and Z coordinates. The definition of these Layouts is achieved simply using a hand-held Joystick or GamePad which drives the probe to one or more key reference cooordinates on the Deck. Adjustments are made, if necessary, and the coordinates confimed using a "Fire" button which records the current position precisely in the Layout definition. It should be emphasised that once defined, these only need adjusting if there is a change to the racks or consumables used by the machine.
There is no limit to the number of Layouts that can be created and it is easy to create new Layouts using HTZ's CCX3 Applications Software.
At the heart of every Beeline SX instrument liquid handling system is a pump to induce fluid flow - precisley. Whilst different types of pump are available, the choice is dependent on the application. The most flexible type is the syringe pump which comprises three main elements namely the Syringe Drive, the Syringe itself and a Valve. The pump is itself is connected to a Sampling Probe, either Fixed (fluid filled) or Disposable Tip (air displacement) and it is this element which is moved around the deck to access samples, reagents and target plates etc. much in the same way as you would with a manual pipette, only faster - in most applications!
A typical fluidic pathway is shown below.
When pipetting with fixed needles, the entire fluid path is filled with liquid. This is referred to as the System Fluid and may be distilled water or a buffer solution which can be used for the preparation of dilutions. The System Fluid, usually supplied to the syringe from an external reservoir, provides a rigid hydraulic connection between the syringe and the probe needle enabling precise pipetting to be performed despite the distance between the two elements. The System Fluid is also used for the washing of the internal and external surfaces of the probe needle inbetween samples and reagents to avoid cross contamination.
The Beeline SX range incorporate one or more high-resolution syringe pumps with 20,000 steps on a 60mm stroke so, when fitted with a 1000µl syringe, provides a resolution of 20 steps per µl , e.g. eg one step movement of the motor equates to a volume of 0.05µl . The syringe drives are designed and manufactured by HTZ and use "ballscrews" for maximum possible life expectancy and to provide the excellent accuracy and precision over a long life time. The ballscrew is the mechanical component which connects the motor to the syringe itself and translates the rotational motion of the motor into the linear movement of the syringe piston and therefore has a critical role to play in maintaining accuracy and reproducibility of the syringe. With minimal routine maintenance, these devices can easily operate for over 20 years of continuous use and longer with typical laboratory duty cycles.
The stepper motor itself provides the motive force to move the syringe piston up and down and the HTZ syringe pump performs a full 60mm stroke in under 0.5 seconds ensuring that smaller syringes can be refilled faster than with most other units available on the market. This ability provides the Beeline SX with a wide dynamic range and the ability to wash pipetting probes (fixed needles) quickly and, in most cases, without resorting to an auxilliary pump to wash probe needles and reduce sample carryover. However, in some applications where the concentration range of the analyte can be very high, e.g. with tumour markers such as HCG, it can be useful to augment the syringe wash with an additional pump to speed up processing. This approach can reduce carryover to less than 1 in 500,000.
Syringes and valves
Although the Beeline SXs are most commonly fitted with a 1000µl syringe, a range of sizes is available (100µl up to 25mls) to cater for different applications. The barrels are all manufactured from precision borosilicate glass and the pistons seals from a special polymer which provides a long service life. For aggressive chemicals such as strong acids and or with certain organic solvents, PTFE piston seals are also available.
The syringe is closely coupled to either a motorised or solenoid valve to control the direction of flow. For many applications, a solenoid valve offers the best performance and life expectancy and provides reliable operation only requiring occasional replacement during preventative service visits.
Two Probe machines have a dedicated syringe drive for each probe.
Peristaltic and disposable syringe based pumps
Alternatively, it is now possible to fit the Beeline SX with an adaptor to work with a standard medical grade disposable syringes. These are ideal for filling jobs requiring complete sterility, minimal calibration and where the complete fluid path needs to be disposed of when completed. In some applications, disposable syringes offer greater accuracy than peristaltic pumps. We can advise which will be the most appropriate for your application.
Probe Type Options
The Beeline SX may be fitted with either 1 or 2 probes. A number of different probe types may be fitted depending on the application including::
Fixed Needle Sampling Probes (eg fluid filled)
Selecting the right Probe Type and Configuration
The Beeline SX can be configured with two independent Z Drives each one with its own probe. The probes can be the same type and therefore be used to double up on the processing speed. Alternatively, they can be fitted with different probe types eg one Fixed fluid filled and one Disposable tip. This can provide the "best of both worlds" as each type has its strengths and weaknesses. Disposable tip probes provide zero carryover and completely avoid the possibility of mixing with the system fluid and becoming "diluted". On the otherhand the Fixed Probe has the advantage of lower running costs, reduced environmental impact, and greater processing speed when performing dilutions. The choice will be driven by the applications, the type of samples being processed and the tests being performed. For example, if performing a large screening program where the positivity rate is very low, an occasional instance of sample carryover can be managed by performing occasional retesting. This can potentially save the laboratory a significant amount of money.
Ultimately, the choice is a process of analysing the costs vs benefits of each in the context of your laboratory's workload and we are of course happy to provide advice on the best option for you.
A choice of level detection options is available on the Beeline SX including:
The best option ultimately depends on the liquids being processed and the requirements of the application. Fixed Probes, based on stainless steel needles, work with either conductivity or capacitance level detectors.
Fixed Sampling Probes
The Fixed, fluid filled probe relies on the system fluid to connect the needle to the syringe and also to wash the interior surfaces. It generally has a wide dynamic range and is able to accurately pipettte volumes in the 5µl to 1000µl range. It is particularly suited to perform basic pipetting and sample dilution processes. The Beeline syringe pump can be primed directly with the dilution buffer this can save time when performing serial dilution and more complex dilution sequences.
Fixed needle probes need washing between samples in order to avoid cross contamination. This is perfomed in a washbath similar to the the type shown below. The needles are positioned in a "blind" well and the syringe pump purges the probe needle with the system fluid. The liquid will rise above the tip of the needle by a few mm and will wash the outside surface as well.
If carryover is a significant concern, an auxilliary pump may be used to pump additional wash fluid through the probe, saving time and achieving improved washing efficiency.
The Beeline SX disposable tip probe terminates with a small device called the Tip Adaptor whose shape matches the internal profile of the tip being used, much in the same way as a tip fits onto the end of a hand-held pipette. A number of different types are available to match the most commonly used tips. Some are single size adaptors designed to fit one specific type of tip and others are designed to fit two or more disposable tip profiles.
The Beeline SX Multi-Tip Adaptor (MTA) caters for a range of disposable tip profiles. This has both internal and external sealing surfaces allowing it to be used with tips that are sealed on the outside diameter (externally sealed tips) such as those manufactured by Apricot Designs* as well as more conventional tips that seal on the inside diameter. This allows the Beeline SX to be loaded with multiple tip sizes and to select whichever tip is most appropriate for the volume being processed.
As a rule, it is best to pipette with no less than 5 to 10% of the total volume of the tip. Therefore, if processing very small volumes only (eg 0.5 to 5 µl ) , tips of 10 to 15µl liquid capacity are recommended. For volumes of 5 to 50µl use a 50µl tip, and for 10 to 200µl use a 200µl tip. Obviously a tip which has a capacity to cater for the largest volume required needs to be part of the Layout if repeat visits are to be avoided.
The SX Multi-Tip-Adaptor is compatible with tips with internal volumes of: 15µl , 50µl , 125µl , 200µl and 1000µl and therefore enables the Beeline SX to pipette volumes from 1µl up to 1000µl with a single probe.
Beeline SX Multi-Tip Adaptor (MTA) shown with some of the compatible tips:
Active Tip Monitoring for additional processing security
The Beeline SX incorporates an optical tip detector which is used for checking that tips have been picked up and ejected succesfully and is also used to check that it remains in position throughout processing. During tip loading, if an empty location is encountered in the disposable tip rack, the probe automatically moves onto the next position and proceeds to search for the next available tip.
Accuracy and Precision
The accuracy and precision (A&P) of automated liquid handlers is influenced by a wide variety of factors. HTZ uses its experience and know-how to develop hardware and software components which ensure that all of its instruments perform well in routine use for many, many years. From the precise control of stepper motors using our own stepper drivers, maintaining tight tolerances on all the fluidic components such as syringes, needles and tips to all of the actual movements of the pipetting probe during the pipetting sequence. All of these parameters ultimately affect the performance and the end-results obtained. Where new applications are being developed we provide specific recommendations on how to achieve the best performance and can supply relevant A&P data to back this up.
With disposable tip probes, gravimetric A&P measurements are usually the best as these have the advantage of being easily cross referenced to international standards (e.g.NAMAS). For fixed, fluid filled probes, photometric or fluorimetric methods provide the most information, especially with respect to dilution accuracy. Sometimes it is necessary to combine both techniques to provide a full A&P profile.
Some typical performance figures for both probe types here:
The Beeline SX incorporates the latest and fastest barcode readers available to provide the ability to automatically read the barcode ID of samples, reagents, controls and other assay related consumables. Sample barcode reading can be performed using either the underarm barcode reader or the Slide-In Rack (SIR). The choice depends largely on the deck space available. See below for further details.
Underarm barcode reader
The underam barcode reader is mounted on the arm of the machine and moves around with the probe carriage. It points downwards onto the deck and is ideally suited for reading upward facing codes on microplates and microscope slides. When used in conjunction with a small mirror integrated into the microplate rack, it can also read the codes on the side of microplates. The barcode reader is a camera based reader and is able to read both 1D (linear) and 2D codes.
Furthermore, the underarm barcode reader can also be used for reading sample barcodes. Samples are loaded onto the deck in one or more sample racks. Each of these is located adjacent to a mirror which runs along the length of the rack and which reflects an image of the sample tubes up to the reader. This simple system enables the SX to use a single barcode reader to automatically read barcodes on all of the components of an assay thereby providing a high level of security with minimum complexity and cost.
This "mirror assisted" barcode reading is fast, reliable and cost effective. However, for applications requiring a Layout with a much higher sample density, we also offer the SIR Barcode Reader Module. See below.
Slide-In-Rack (SIR) Barcode Reader Module
The SIR barcode reading module is a separate mechanism which is mounted on top of the right-hand side of the Deck. It comprises a number of locations which accept special sample tube carriers. Each carrier has a capacity for 16 barcoded samples and each of these carriers is loaded into the SIR module in sequence by sliding it into its allocated docking position. The position of each sample in the rack is determined by reading "Sentry" barcodes on either side of each sample and which form part of the rack.
The SIR module incorporates an ultra-high speed sample barcode reader and a linear drive to automatically position the reader at the optimal distance for highest reliability of reading barcodes whatever printing density has been used. As each rack is loaded onto the SIR module, the barcode reader adjusts its position accordingly to maximise the speed and reliability of the barcode reading process. This is especially valuable for the 288 position rack (18 racks each with 16 tubes) where relying on the depth of field of the reader would result in lower performance and a lower succesful read rate. Other features include:
Audible feedback tones confirm correct scanning enabling operator to perform the loading process without having to refer to the PC.
Three different capacities: 96, 160 and 288 sample positions
Standard Carriers accommodate tubes with diameters between 10mm to 16mm e.g. Sarstedt 2.0ml up to 16mm Vacutainers/ Vacuette tubes. Others are available by special request.
Both the underarm and SIR barcode readers are fully configurable for all code symbologies commonly used in the laboratory such as Code 128, Interleaved 2 of 5, Code 39 etc . Furthermore they are fully programmable and allow a vast number of options for manipulating codes before transmission to the Beeline e.g. removing or adding prefixes, checksums etc if required.
Beeline SX Deck Capacity for some common Layouts
The capacity for different target racks depends largely on the choice of barcode reading option and the number of samples that have to be processed within 1 batch. The mirror racks take up relatively more space than the SIR racks but this option is significantly lower cost so it is worth considering if it fits the workflow requirements of the laboratory.
The Beeline 300 SX has approximately 50% lower capacity than the corresponding 500 SX owing to the smaller Deck size.
The following table illustrates the typical capacity of a number of different configurations. For example, Layout #1 is based on 3 of the 32 position "mirror assisted" sample racks. In addition to these, the Deck can accommodate 3 Microplate (SBS) type racks and still leaves room for a small reagent bottle rack. If working with disposable tips, one of the microplate locations will be needed for the tip rack leaving two positions available for target microplates. However, note that by opting for the SIR rack instead, as in Layout 2, the target capacity doubles up to 6 microplates.
The Beeline SX is operated through one of our Applications Suites. These provide an easy to use programming environment and enable the Beeline SX liquid handlers to perform just about any liquid handling task.
There are two main applications suites namely, CCX and BGX, and each has a slightly different emphasis and scope. For example, CCX was originally developed for IFA and ELISA applications and caters for pipetting tasks where sample specific processing is required e.g. where a worklist controls the number of dilutions of an individual sample. Whereas BGX, originally developed for Blood Grouping tests, is optimised for applications where a given sample is pipetted into multiple wells but where all the samples processed by a given test are all processed in the same way.
CCX is now in its third major release (hence CCX3) and has been enhanced over the past 10 years to provide ever increasing levels of flexibility and security.
For more information click here >>>> CCX3
A number of hardware options are available to suit the needs of specific applications including different probe types, racks, pump types etc.