Solutions for Molecular Diagnostics

Transcription

1 Solutions for Molecular Diagnostics Certified Quality Products FOR MOLECULAR DIAGNOSTICS Off-the-shelf and Custom Solutions for Manufacturing Diagnostic Kits ISO 9001 and ISO production in class 7 and 8 cleanrooms Certified, state-of-the-art manufacturing for medical devices Custom product design and manufacturing of injection moulded parts Smooth transition from idea to product Modular plate and sealing solutions available off-the-shelf Quick and easy kit construction 4titude Ltd. The North Barn Surrey Hills Business Park Damphurst Lane Wotton Surrey RH5 6QT T: +44 (0) F: +44 (0) E: info@4ti.co.uk

2 Solutions for molecular diagnostics 4titude provides off-the-shelf and custom made consumables for molecular diagnostic kit manufacturing. We design and produce innovative solutions which address the needs of kit manufacturers and end users at the same time. Our automation friendly consumables can be handled robotically at the manufacturers site and later be divided into smaller sections to suit the end users needs. 96well and other plate formats for different applications including PCR Custom formats available on request Plates can be divided into smaller plate sections, e.g. 8-strips & single tubes 2D coding, barcoding and colour coding for tracking of samples Variety of sealing options for safe storage and shipping Meeting the demands of manufacturers & end users

3 4titude manufacturing & quality standards 4titude are ISO 9001:2008 & ISO 13485:2012 certified to manufacture and supply consumables for the life sciences sector. Our management systems comply with the requirements to produce medical devices which we sell to diagnostics companies of all sizes including multinational corporations. We also provide complete custom design solutions from prototyping to tool design and contract manufacturing. Manufacturing standard ISO 9001:2008 & ISO 13485:2012 certified Process validation & mapping Fully document controlled manufacturing processes Statistical analysis of production processes Continuous improvement programs Injection moulding in ISO class 7 & 8 cleanrooms Virgin, medical grade polymers Quality standard 4titude performs visual, physical and biological tests to ensure that our consumables are contamination free, as well as the integrity of the products at all times. Consumables are certified free from bacterial and human genomic DNA, nucleases and pyrogens Skirted micro- and PCR plates meet the SBS standard footprint PCR inhibition tests are performed on all polymers used Leak tests are performed on every well of every PCR plate White-well plates are checked for low background fluorescence

4 FrameStar Break-A-Way - Division brings flexibility! The 4titude Break-A-Way plate range offers all the advantages of our popular FrameStar 2-component products in a format which can easily be divided into segments, strips or even individual tubes. This product range enables reagent dispensing to be automated in plate format, then post-dispensing the plate can be divided, as required, by either the manufacturer or the end-user. Dividable horizontally, vertically or both 0.1 or 0.2 ml tube volume options A choice of colour frames available Clear or white wells Sterilisation options Available as pre-cut strips, FrameStrips Sealable with strip caps, adhesive or heat seals Plate segmentation can be automated 2D coding offered Fig. 1 FrameStar Break-A-Way plates Fig. 2 FrameStar Break-A-Way Duo, dividable both horizontally and vertically Fig. 3 FrameStrip 2D coded FrameStar Break-A-Way plates - an excellent choice for kit manufacturers looking for maximum flexibility. Standard 96well PCR Plates - More than just standard! The thin-walled tubes of our standard 96well PCR Plate maximise heat transfer and the raised tube rims facilitate sealing. Colour options White version for optical applications Available as segments of 8/16/24/32/48 wells Available freely dividable into sections or strips (Tear-A-Way plate) Sterilisation options Sealable with strip caps, adhesive or heat seals Fig. 4 Available in clear, purple, red, blue, green, yellow and white with black alphanumeric lettering Fig. 5 Segments of the unskirted standard profile plate Fig. 6 96well PCR Plate also available as Tear-A-Way versions, dividable in 8strip or 12strip direction Standard PCR plates - an extremely cost effective solution to improve the flexibility of workflows.

5 Vari-Plates - Holding it together! The 4titude Vari-system offers total flexibility in plate usage. It allows the user to insert or remove strips of 8 tubes from a plate frame. Choice of frame styles to suit most instruments Clear or white well strips Pre-loaded frames Sealable using strip caps, adhesives or heat seals 0.1ml tube volume Fig. 7 Vari-Strips with white tubes for highest sensitivity Vari-Plates - the ultimate in flexibility. Plate Cutter - Split it your way! The plate cutter can be used to divide a plate, whether sealed with caps, adhesives, heat seals or unsealed. Plates can be divided into any format as required: segments, strips or individual tubes. With heat or adhesive sealed plates the plate cutter can also be set to divide the seal only, without damaging the plate itself. Semi-automated Simple division of Break-A-Way and Tear-A-Way plates Available in 8 or 12 strip format Separates plates into segments, strips or single tubes Suitable for division of seals applied to PCR style plates Compatible with plates sealed with caps, adhesives or heat seals Fig. 8 4titude Plate Cutter Fig. 9 Step 1: Place the plate (e.g. Vari- Plate) on the shuttle, close the shuttle Fig. 10 Step 2: The Plate/Seal is cut into segments Fig. 11 Step 3: Remove the cut plate from the device 4titude Plate Cutter - product design answering practical demands.

6 Heat Sealing - The ultimate bond! With 4titude Heat Sealing systems samples can be sealed for evaporation free heating (including PCR), secure storage and shipping. Instrumentation and compatible sealing materials are available from stock but bespoke heat sealers, seal formats and materials can also be designed and manufactured on request. Our unique InterSeal system combines heat sealing with adhesive sealing for the ultimate in secure reagent transport and flexibility of end user handling. Please refer to the next page to see a typical application of the InterSeal. Catalogue and custom Heat sealers Robotic integration compatible Peel and pierce options Optical and gas permeable options Rolls, sheets, strips or custom seal formats Thermal transfer printing available Fig. 12 a4s Automated roll heat sealer Automation of seal division and removal available Fig. 15 InterSeal double sided adhesive film Fig. 13 4s3 Semi-automated heat sealer Fig. 14 Custom heat sealer Fig. 16 Custom printed seal Heat Sealing - the gold standard method for plate and tube sealing.

7 A typical workflow At the kit manufacturer I. Vari-Plate loaded with Vari-Strips can be filled with reagents on a robotic system II. Heat sealing with 4s3 Semi-automated heat sealer III. Vari-Plate sealed with pierceable seal IV. Apply adhesive InterSeal to the plate V. Cut seals with the 4titude Plate Cutter VI. Remove strips from the Vari-Plate. Pre-filled strips ready for diagnostics. At the point of diagnostic use VII. Remove InterSeal protective layer VIII. Pierce the foil and add the sample to the strip pre-filled with reagents IX. Reseal strips with foil X. Ready for PCR analysis! The Vari-Plates allow for 8well strips to be processed like a 96well plate on robotic systems while the end product is in flexible 8well format. Sealing the plates with a heat seal results in lowest evaporation and best possible long-term storage. With the use of a pierceable seal, samples can easily be added at the point of diagnostic use. The protective InterSeal makes sure there will be no damage to the seal during transportation. After removal of the InterSeal protective layer, samples are added and the strips are resealed for subsequent PCR analysis. In this workflow the 4titude Plate Cutter only needs to cut the seals, it could also cut seals and plates if FrameStar 96well Break-A-Way plates were used instead of the 8well Vari-Strips in Vari-Plates.

8 Case Study 1 Customer: A company producing a human diagnostic kit for the detection of infectious disease. Kit manufacturing requirements: Kit components need to be dispensed into PCR plates to produce an IVD/FDA approved kit subject to the highest quality standards. Requirements of the final product: The kit is for use on an automated diagnostic instrument, automation of plate handling, liquid dispensing and sealing is required. Key issues to be solved Automated handling: Automated plate handling and liquid dispensing requires the use of a rigid automation compatible qpcr plate Heat Sealing: The use of highly infectious agents requires a secure plate sealing method which can be integrated into an automation system 4titude products used Code Description 4ti-0951/SBC FrameStar Roche LightCycler 480 compatible 96well PCR plate 4ti-0665 a4s automated roll heat sealer 4ti-0575 Clear Weld Seal Mark II qpcr Analysis: A transparent, permanent seal is needed suitable for qpcr analysis Processes of the workflow AUTOMATION FRIENDLY 1. The reagents are dispensed in the FrameStar Roche LightCycler 480 compatible 96well PCR plate using a liquid handling robot. The 2-component construction of FrameStar plates is ideal for automated handling. This plate does not warp, following amplification or heat sealing, enabling accurate automated plate handling and liquid dispensing. SAMPLE TRACKING 2. The plate is barcoded on one side to enable sample tracking throughout the workflow. Barcodes can be applied on any side of a plate and any 10 digit specification can be used, enabling true efficiency of sample tracking. SEALING SOLUTIONS 3. The a4s automated roll heat sealer is integrated within, and controlled by, the customer's automated system and is used to apply Clear Weld Seal Mark II to each plate. Up to 5000 seals can be applied consistently without intervention using this set up and the seal applied provides a 100% leak proof seal for secure handling of infectious material. OPTIMISED FOR QPCR 4. The plate is placed on a Roche LightCycler for qpcr analysis. The white wells of the plate ensure no well to well signal contamination occurs, the clear seal is optically clear for maximum signal detection. 1./ FrameStar 480/96 Plate Filling with reagents Sealing with Clear Weld Seal Mark II qpcr analysis Fully Automated Liquid Handling Robot Integrated a4s Heat Sealer Roche LightCycler

9 Case Study 2 Customer: A healthcare company in Germany Kit manufacturing requirements: Our customer manufactures a number of kits for human diagnostics. Requirements of the final product: Typically, the kits are utilised at point-of-care by commercial laboratories for a varying number of patients per day. These laboratories need to use kits on a large variety of standard thermal cyclers. Key issues to be solved Suitable PCR plate: A standard non-skirted PCR plate format is required for flexible use in consumer laboratories on a variety of thermal cyclers. The end user laboratories handle varying numbers of patient samples and do not wish to utilise a full 96well plate. Shelf life: A long shelf life is necessary to enable shipment of the kits around the world and to suit the end-user. 4titude products used Code 4ti-0750/8 4ti-0750/16 4ti-0750/24 4ti-0750/32 4ti-0750/48 4ti-0752 Description 8well pre-cut PCR plate segments 16well pre-cut PCR plate segments 24well pre-cut PCR plate segments 32well pre-cut PCR plate segments 48well pre-cut PCR plate segments Strips of 8 domed caps Product identification: Each kit type must be easily identifiable during manufacturing Processes of the workflow 1. 4ti-0750/# plate segments are filled with reagents using a semi-automated liquid handler. A number of segments can be placed next to each other in each 96well plate holder for maximum efficiency. 2. 4ti-0752 strip caps are used to seal the segments for secure shipping to the customer. Strip caps ensure a secure leak proof seal for shipping and storage. 3. The customer adds a DNA sample and then reseals the strip with the previously removed strip caps for PCR analysis. 4. The customer removes the strip caps following PCR and removes the PCR product for downstream analysis.

10 Ordering information - Make your choice! Code Description Instrumentation our catalogue instrumentation, custom units are available 4ti ti ti ti ti s3 Semi-automated sheet heat sealer; Accessories: standard and custom plate/tube holders are available a4s Automated roll heat sealer; Accessories: standard and custom plate/tube holders are available Plate Cutter; Accessories: standard and custom cutter heads are available Rackscanner for reading 2D coded racked tubes Handheld barcode reader, can read any barcode, linear or 2D Plates Tear-A-Way Plates 4ti-0750/TA 4ti-0750/W/TA 4ti-0750/TA/12 Tear-A-Way 96/8, 96well non-skirted PCR plate, tears into segments or strips of 8 tubes, 0.2 ml wells, clear polypropylene, black lettering Tear-A-Way 96/8, 96well non-skirted PCR plate, tears into segments or strips of 8 tubes, 0.2 ml wells, white polypropylene, black lettering Tear-A-Way 96/12, 96well non-skirted PCR plate, tears into segments or strips of 12 tubes, 0.2 ml wells, clear polypropylene, black lettering FrameStar Break-A-Way Plates 4ti ti ti ti ti-1300/X FrameStar Break-A-Way 96well semi-skirted qpcr plate, 0.2 ml clear wells, clear frame, 2-component ultra rigid, high performance plate. Snaps into segments or strips of 8 tubes, Colour frames available FrameStar Break-A-Way 96well semi-skirted qpcr plate, low profile 0.1 ml white wells, black frame, 2-component ultra rigid, high performance plate FrameStar Break-A-Way low profile 96well semi-skirted PCR plate, low profile 0.1 ml clear wells, clear frame, 2-component ultra rigid, high performance plate. Snaps into segments or strips of 8 tubes. Colour frames available FrameStar Break-A-Way low profile 96well semi-skirted qpcr plate, low profile 0.1 ml white wells, black frame, 2-component ultra rigid, high performance plate. Snaps into segments or strips of 8 tubes FrameStar Break-A-Way Duo 96well semi-skirted PCR plate, 0.2 ml clear wells, black frame, 2-component ultra rigid, high performance plate. Snaps into segments, strips or individual tubes Plate segments 4ti-0750/8/C 4ti-0750/16/C 4ti-0750/24/C 4ti-0750/32/C 4ti-0750/48/C 8well PCR plate, 0.2 ml wells, clear polypropylene, other colours available 16well PCR plate, 0.2 ml wells, clear polypropylene, other colours available 24well PCR plate, 0.2 ml wells, clear polypropylene, other colours available 32well PCR plate, 0.2 ml wells, clear polypropylene, other colours available 48well PCR plate, 0.2 ml wells, clear polypropylene, other colours available Vari-Plate system 4ti-0753/757 4ti-0753/C/757 4ti-0757-F 4ti ti-0753/C 4ti ti-0754/C Vari-Plate skirted white PCR plate frame, loaded with 12 removable Vari-Strips of 8 tubes, white polypropylene, 0.1 ml wells Vari-Plate skirted white PCR plate frame, loaded with 12 removable Vari-Strips of 8 tubes, clear polypropylene, 0.1 ml wells Vari-Plate skirted white PCR plate frame Vari-Strips of 8 low profile PCR tubes, white polypropylene, 0.1 ml wells, with strips of 8 clear flat optical caps Vari-Strips of 8 low profile PCR tubes, clear polypropylene, 0.1 ml wells Vari-Strips of 8 low profile PCR tubes, white polypropylene, 0.1 ml wells Vari-Strips of 8 low profile PCR tubes, clear polypropylene, 0.1 ml wells, with strips of 8 clear flat optical caps

11 Sealing solutions Heat seals a selection from our vast range of heat seals, available as sheets or rolls 4ti ti ti-0531/GR 4ti ti ti ti-0575/FS Peel-Seal Heat Sealing Foil, suitable for PCR, peelable, sheets. Also available in roll format Pierce-Seal Heat Sealing Foil, suitable for PCR, pierceable, sheets. Also available in roll format Pierce-Seal grid Heat Sealing Foil, suitable for PCR, pierceable, sheets. With printed grid reference for improved sample location Clear-Seal Heat Sealing Film, optically clear, suitable for imaging and qpcr, peelable, sheets. Also available in roll format DMSO Resistant Peel Seal, Heat Sealing Foil, solvent resistant, peelable, sheets. Also available in roll format INDI 96 Heat Sealing Foil, seals 96 individual tubes racked and 96 well plates, sheets FrameSeal containing Clear Weld Seal Mark II Heat Sealing Film, suitable for imaging and qpcr Adhesive seals a selection from our vast range of heat seals, available as sheets or rolls 4ti ti ti ti-0516/# 4ti ti ti-0566 InterSeal, double sided adhesive plate seal, for use with pierceable heat seal, sheets PCR Adhesive Plate seal, clear film, suitable for PCR, peelable, sheets Resistant Foil Adhesive Plate Seal, DMSO and solvent resistant, peelable, sheets Clear Gas Permeable Imaging Seal, Adhesive Plate Film, 24, 96 or 384 optically clear moisture resistant windows, peelable, sheets, sterile PCR Foil Adhesive Plate Seal, suitable for PCR, peelable, pierceable, sheets Optically Clear Adhesive Plate Seal, suitable for imaging and qpcr, pressure activated adhesive, peelable, sheets Pierceable Clear Film Adhesive Plate Seal, 96 cross-cut windows, suitable for 96 well plates, peelable, pierceable, sheets Processing options 4ti-####/SBC 4ti-####/DBC 2D coding Custom barcoding Sterilisation Custom packaging Our 4titude single bar code can be applied to any plate with a skirt or semi-skirt. The barcode is in linear (code 128) format 4T with no repeats guaranteed. The label also shows the code in human readable form. The label will be applied on the south side of the plate. Our 4titude double bar code can be applied to any plate with a skirt or semi-skirt. The barcode is in linear (code 128) format 4T with no repeats guaranteed. The label also shows the code in human readable form. An identical label will be applied on the south and east side of the plate. We are able to custom 2D code a number of our products, such as the base of our cluster tubes or the caps of our PCR tubes. Please enquire. Our custom barcoding service can add a barcode of your choice in the position of your choice. A number of our products are available sterile from stock. We can also offer custom sterilisation by gamma irradiation or ethylene oxide treatment, please enquire. We can provide a number of custom packaging services. These include specified bagging quantities and white box packing. Please enquire.

12 License Statement & Trademarks Disclaimer: FrameStar FrameStrip, Tear-A-Way, Vari-Plate, Vari-Strips and 4s3 are registered trademarks of 4titude Limited; LightCycler is a registered trademark of Hoffmann-La Roche. Designated trademarks and brands not mentioned above are the property or their respectice owners. FrameStar PCR plates are covered by one or more of the following U.S.patents or their foreign counterparts, owned by Eppendorf AG: US Patent Nos. 7,347,977 and 6,340,589 Distributed by: Image credits: hywards - Fotolia.com 4ti-FL-0006 Brochure Consumables for MD en2/0/1/ OP 4titude Ltd. The North Barn Surrey Hills Business Park Damphurst Lane Wotton Surrey RH5 6QT T: +44 (0) F: +44 (0) E: info@4ti.co.uk