MAGNUS INNOVATIVE HYBRID PROCESSING TECHNOLOGY The MAGNUS is the result of Milestone’s 15 years of know-how in applying microwaves to tissue processing. The MAGNUS provides the ideal combination of automatic processing performance, reagent efficiency and environmental sensitivity, with the morphology and quality that histologists and pathologists expect. SIMULTANEOUS MICROWAVE PLUS RESISTANCE HEATING The retort’s resistance heated base plate speeds up the ramping time to the pre-set processing temperature, followed by ultrarapid dehydration/clearing steps carried out by microwave technology for faster turnaround. Early morning: process on-demand with microwave technology: urgent specimens and small biopsies in as little as 60-120 minutes. This operation will cover about 30-40% of the average lab workload. Specimens can be ready for embedding, cutting, staining, allowing same-day diagnostic reporting. Late afternoon load any remaining specimens in your fixative of choice and set Delay Start. In the early pre-dawn hours Pathos will automatically start processing. All specimens will be ready to be embedded, cut, stained at the start of the workday. RESISTANCE HEATING ONLY The MAGNUS operates as a conventional overnight tissue processor. Its parameters can be set to fit your specific workflow requirements or to fulfill all CAP/ASCO guidelines for assessing Her-2 and all Consensus Recommendations for ER testing in breast tissues. The MAGNUS can be set up to operate as a standard, conventional, resistance-heating processor. Processes breast tissue for assessing Her-2 in full compliance with CAP/ASCO guidelines and FDA Her-2 approved testing, in accordance with heating mode, temperatures, and reagent types. Follows standard validation procedures for new lab instrumentation. UNMATCHED PROCESSING TIMES SIX TIMES FASTER THAN CONVENTIONAL PROCESSING SPECIMEN THICKNESS RAPID PROTOCOLS Transplant (less than 1mm) 60 minutes (including fixation) 1 mm 65 minutes Add 10 minutes to include fixation 3 mm 155 minutes Add 30 minutes to include fixation 5-6 mm 290 minutes Add 60 minutes to include fixation • Fully automated processing in overnight and rapid mode • Customized reagents type and sequence • Up to 300 standard cassettes or up to 24 supermega cassettes • Any type of tissue, up to 5mm thickness in split rack (140/210) or random basket rack (300) • Any type of tissue, up to 8mm thickness in supermega cassettes rack (24) UNRIVALLED QUALITY MAGNUS processes biopsies with specific optimized protocols to consistently assure the highest quality standards. EASY TO USE MAGNUS software: the essence of simplicity. STEP 1 Load the rack with up to 210 cassettes STEP 2 Select favourites STEP 3 Select a protocol from the favourites list STEP 4 Enter the number of cassettes and press Start. That’s all. FLEXIBLE PROCESSING LOAD CAPABILITIES MULTIPLE RACK CONFIGURATIONS ARE AVAILABLE TO MEET SPECIFIC REQUIREMENTS 210 Cassette type Standard 210 Split rack. Fits most embedding centers 300 Cassette type Up to 300 random For microwave overnight processing 24 Cassette type 24 Supermega Suitable for whole mount (e.g. prostate) 40 Cassette type 40 Slim Supermega Suitable for whole mount (e.g. prostate) 45 Synergy Synergy is a revolutionary method to automatically embed tissues as part of the processing protocols. This method is applied to Milestones rapid tissue processors MAGNUS and Logos. Thanks to a dedicated rack and consumables, the same processor unit can achieve automatic embedding. All kinds of tissues and dimensions can be processed and embedded with this method. Specimens are placed in the mold during grossing. Much like embedding. A special pad is placed on top of the tissue to maintain positioning. The cassette is clipped in place as a cover of the mould. The mould plus cassette is then inserted into the Synergy rack. The specially designed rack is angled during the fixation and regent steps so fluids flow in and out without retention. When the rack moves to wax the leverage system of the rack allows the molds go to a flat position. This collects and holds the necessary paraffin to embed the tissue. The cassettes are then simply removed from the rack and placed on a cold plate. After ten minutes the cassettes are easily removed from the disposable moulds and are ready for cutting. Synergy Benefits Fully automated processing and embedding in one unit Optimal flat positioning of small biopsies such as needle cores Tissue is handled once at grossing. Accidental tissue loss during processing and embedding is eliminated. The Milestone Xylene Free Processing Protocols Optimized xylene free protocols are the heart of the MAGNUS efficiency. Using only four reagents each protocol has been developed to provide superior quality. Small biopsies can be processed in just over an hour. The single Ethanol dehydration step eliminates over processing for your most delicate specimens. Larger or fatty tissues up to 5mm may be processed in as little as 8 hours with quality that may surpass results seen in twelve hours when processed conventionally. The Xylene free protocols utilize a flush phase and two rinses that are used to help maintain the reagent integrity. When combined with a reduction in the overall time of the active steps due to application of gentle heat Milestone is able to achieve rapid tissue processing that delivers high quality with the added advantage of xylene free processing. These protocols have been developed and standardized across the Milestone platforms for over thirteen years. The following outlines the steps used for rapid xylene free processing. Fixation: 10% Neutral Buffered formalin is heated to 50C during the optional heated fixation phase. The length of the fixation phase is dictated by th sample size. Standardized and complete fixation can be achieved through use of presoak and the heated fixation phase. Flush: Seventy percent alcohol is utilized for 1 minute at ambient temperature to rinse off formalin and eliminate buffer salts from precipitating in subsequent alcohol steps. Flush is run as part of every protocol and eliminates the need for a weekly hot water flush. Rinse: Two Ethanol rinses of two minutes each are used to eliminate water carryover from the flush step. This allows for the use of a single dehydration step. Dehydration: Ethanol is used for the single dehydration step. Heating to 65C provides rapid but gentle dehydration. Clearing: Isopropyl Alcohol is used as the clearing reagent in the xylene free rapid tissue processing protocols. Heated to 68C the Isopropyl extracts lipids and is mixable with the subsequent paraffin step. Wax infiltration: A single paraffin is used for wax infiltration. Vacuum allows for improved infiltration with moderate temperatures During wax infiltration the Isopropyl evaporates out of the paraffin. The Xylene free protocols mean that there is no solvent present to break down the wax. Since Isopropyl will readily evaporate out of the wax a weekly cleaning cycle is effective in maintaining wax integrity for up to a month. The efficiency of the MAGNUS allows for improved workload management. The rack is automatically moved from the processing retort to the paraffin retort. When the protocol is complete the next rack can be immediately loaded without waiting for a cleaning cycle to be performed. With processing times of just over an hour for 1mm biopsies multiple processing cycles can be performed daily to balance workload throughout the day. This allows for improved turnaround times and efficiency in the lean histology lab. The value of MAGNUS for quality improvement Rapid tissue processing and Lean Histology are reported in the following publications. Optimization of Fixation and Processing of Biopsy gun Prostate Needle Biopsy Specimens. RJ Zarbo, NS Gupta, R Varney, N. Mian, S.RiN. Draga, O Alassi, A ormsby, R D’angelo Department of Pathology, Henry Ford Health System, Detroit, Michigan. Abstract Background: Consistency of nuclear and cytologic detail in prostate needle Biopsy specimens is a critical aspect of histopathologic diagnosis. The preanalytical parameters of formalin fixation from time of surgical procedure are largely uncontrolled and inadequate fixation may contribute to less than optimal histology when using same-day rapid tissue processing. To accommodate this unstandardized variable by defaulting to overnight fixation of Biopsy gun prostate needle biopsies negates the advantage of rapid cycle processing. Design: We performed Biopsy Gun (Bard Peripheral Vascular, Inc. Tempe, AZ) needle biopsies of fresh clinical prostatectomy specimens to test 18 pathway variations of tissue fixation and processing. Needle (18G) cores obtained from the posterior aspect of glands (8 per side) were 1 mm or less diameter and averaged 15-18 mm length. To control for variation in fixation time and mimic air-drying, cores were placed on saline soaked gauze initially before testing combinations of no fixation other than on processors, timed tissue fixation at room temperature, desktop microwave formalin fixation for 3.5 minutes (Model EBS42850, Energy Beam Sciences, East Granby, CT), controlled heated fixation for 30 minutes at 37°, 45° and 50°C (FixMate, Milestone Medical Technologies, Inc, Kalamazoo, MI/Sorisole, Italy) and processing on two microwave enhanced instruments, Tissue-Tek Xpress (Sakura Finetek USA, Inc, Torrance, CA) and MAGNUS (Milestone Medical Technologies). Quality assessments were made of ease of embedding and microtome sectioning and histopathologic variables of haematoxylin and eosin staining intensity, homogeneity, nuclear preservation, nucleolar prominence, autolysis or thermal artifact. Microscopic sections were evaluated by one GU pathologist. Microscopic quality was scored on a 10-part scale. Results: With the exception of the FixMate heated and timed fixation tests at 37°C and 45°C, all combinations gave inconsistent and spotty unacceptable, suboptimal to good microscopic preparations no matter the variable manipulated. The higher 50°C test of heated formalin fixation resulted in an artifact of nuclear chromatin that was dark and smudgy. The histologic quality at 37°C was judged slightly superior to 45°C. No significant difference in quality of tissue microtomy or histologic preparation was noted for either microwave tissue processor. Conclusions: Enhanced consistency in the quality of histologic preparations using rapid microwave processors is obtained when prostate needle biopsy fixation is standardized with controlled time and temperature of fixation. Lean Design of Experiment Background • Increased volume of needle biopsy cases and clinician (customer) requests for quicker pathologic diagnoses prompted investigation into reducing the overnight tissue fixation process • Inadequate fixation contributes largely to less than optimal morphology • Needed to develop a method to optimize fixation without compromising morphological appearance on the glass slides • Needle cores obtained from clinical prostates and processed according to three trials • Trial1- five needle core samples, Trial 2 with four core samples and Trial 3 with eight core samples (Fig. 1) • All cores microscopically evaluated as a six point scoring scale. A 37C formalin fixation temperature provides a slightly superior quality of histologic section than at 45C or 50C • Enhanced consistency in the quality of histologic preparations using rapid microwave processors is obtained when prostate needle biopsy fixation is standardized with controlled time and temperature of fixation • Fixation of prostate needle biopsies can be expedited from overnight to same day processing Validation of Histology Tissue Processing and Stain Quality of Rapid –Cycle Microwave Processor in Lean Continuous Flow Operations Pathology report timeliness can be enhanced by technology that reduces time waste in histology. The largest delay is overnight fixation and prolonged processor times. These throughput bottlenecks can be targeted by integrating tissue processors capable of rapid-cycle times especially when aligned with continuous flow Lean work design. Design: Evaluation of a rapid-cycle microwave processor was performed at Henry Ford Hospital Histology Core Laboratory with aims to 1) integration of processor into continuous flow work process;2)compare specimen quality in split samples processed by conventional overnight processors and the rapid-cycle instrument. We assessed technical quality of block processing, slide cutting and H+E staining by histotechnologists and quality of H+E, special and immunohistochemical stains by pathologists with a standard input form. 238 specimens were dissected fresh and split by 2 PAs. 3 part scheme with free text comments was used for histology assessment (High, Average, Low Quality) and pathologists' microscopic evaluation (Acceptable, Inferior, Unacceptable for Diagnosis). Analysis was stratified by tissue type and processed thickness. Conclusion: This study validates the technical, H+E and immunohistochemical stain quality obtained with a new rapid cycle microwave processor over a range of tissue types and processed thicknesses. The abbreviated cycle time including fixation (1.25-3 hours) facilitates the Lean approach to continuous flow processing with continuous slide production. Used in this fashion, the instrument facilitates potentially shorter report turnaround times compared to conventional overnight processing Results: In 238 tissues (fat, liver, placenta, ovary, colon, stomach, endometrium, cervix, ovary, uterus, prostate, testis, skin, thyroid, gallbladder, soft tissue, heart, POC, lymph node, salivary gland, thrombus, oesophagus, lung, larynx), no significant quality differences were noted between rapid cycle and conventional processors in any parameter assessed in 49 needle biopsies (1mm), 28 small biopsies (2mm) and 161 large specimens (3mm). Technical cutting quality was at variance in a minority, better in 9 cases from the rapid-cycle processor with embedded tissue being less dry or brittle whereas only 3 of the conventionally processed tissues were noted of better cutting quality. Pathologists detected no difference between the 2 types of processed specimens in any H+E stain, 10 special stains and 30 Immunostains. None were of inferior technical quality for diagnosis.