1

PATHOSA U T O M A T I C , R A P I D M I C R O W A V E H I S T O P R O C E S S O R

F O R S P E C I M E N S U P T O 5 M M I N T H I C K N E S S

M I L E S T O N E

C O M P A S S I O N A T E T E C H N O L O G Y F O R S A M E - D A Y D I A G N O S I S

1

In 1909......G. Arendt* described the first histoprocessor.By 1910 all the main techniques had beenworked out and many procedures then in useare still followed in virtually unchanged formtoday.**Conventional histoprocessors have simplyautomated manual procedures withoutmaking efforts to reduce histoprocessingtimes.

* G Arendt (1909) Apparat zur selssttaetigen Fixierung und Einbettung mikroskopischer Praeparate, Munchen. med. Wochschr. 56:2226-2227

** A History of Microtechnique - Brian Bracegirdle. Science Heritage Ltd., 1987 Publisher

Today...Welcome to PATHOS. The future is here.The revolutionary automatic microwave enhanced histoprocessor.

The PATHOS is the result of Milestone’s 13 years of experience in applying microwavesto histoprocessing and the hundreds of semi-automatic RHS microwave histoprocessorsinstalled worldwide. The PATHOS provides the ideal combination of processingperformance, reagents efficiency, and environmental sensitivity, without sacrificing themorphology and quality histopathologists expect. The PATHOS is not just a leap forward in histoprocessing, it is a step in the right directionfor the lean histology laboratory. The implications are amazing:

- Same-day processing for same-day diagnosis.

- Reduced patient stress.

- Improved patient care.

- Greener and safer work environment (no xylene).

Milestone’s pioneering work in vacuum histoprocessing resulted in 1997 in an EuropeanPatent EP 822 403 and US Patent 6042.874. Milestone’s process is described in thearticle “Ultra-Rapid Microwave/Variable Pressure-Induced Histoprocessing: Description ofa New Tissue Processor” Journal of Histotechnology, Vol. 21, No. 3, Sept. 1998by F. Visinoni et al.

1998: Milestone URMFirst microwave rapid histoprocessorEuropean Patent EP 0822403 dated 29.07.1998US Patent 6,042,874 dated Mar. 28, 2000

Milestone: a catalyst of change tomake a difference in thetreatment of the patient.

2006: Milestone PATHOSAutomatic microwave histoprocessorEuropean Patent 1605243 dated 14.12.205US Patent 7,075,045 dated July 11th, 2006

Milestone is committed to helping patients byproviding histologists and pathologists withinnovative, compassionate technology toenhance diagnostic pathology.

MILESTONEA Company

with a Caring Goal

2

PATHOS small biopsies

PATHOS regular biopsies

Conventional regular biopsies

Specimen thickness

1.5 mm

3 mm

5 mm

Pathos processing time for up to 210 cassettes

30 minutesAdd 10 minutes to include Fixation

80 minutes Add 25 minutes to include Fixation

210 minutes Add 40 minutes to include Fixation

PATHOS REDUCES SPECIMEN TURN-AROUND TIMESFOR A MORE TIMELY DIAGNOSIS AND IMPROVED PATIENT CARE.

PATHOS Creating a Class of Its Own.

Unmatchedprocessing times.

6 times faster than conventional histoprocessing.

3

Staining properties of PATHOS microwave processed specimens are excellent for H&E, HC, IHC, FISH.

Adenocarcinoma.Immunostaining of Cytokeratin CAM5.2following microwave epitope retrieval.Microwave processed in 2 hours. x 400.

Bowel biopsy,microwave processedin 90 minutes. Alcian blue microwave staining of mucin producing cells. x 400.

Colonic biopsy,microwave processed in 30 minutes. H&E x 400.

Invasive DuctalCarcinoma of breast,microwave processedin 90 minutes. H&E x 400.

Benign breast tissues, microw a v eprocessed in 2 hours. Note the excellentmorphological preservation H&Ex200.

Ductal carcinoma in situ. Needlebiopsy, microwave processed in 30minutes. Note the preservation andquality of the morphology.

Breast cells HER2 amplification detec-tion by FISH processed by microwaves.Red-labeled HER2 probe, originalmagnification x 800

Breast cells HER2 amplificationdetection by IHC, processed bymicrowaves. Hematoxylin counterstain, originalmagnification x 400.

Metastatic breast tumour inlymphonode, microwave processedin 2 hours. H&Ex400 .

Superior histoprocessing of fatty tissues (e.g. breast).

SAFETY- Xylene-free processing.- Fixation with either formalin or Milestone’s FineFIX,

the formalin substitute for enhanced molecular studies.4

SIMPLICITY- No need to change your grossing procedure.- No need for special grossing tools. - Fully automatic operation.- Software driven advanced reagents management system.- No cleaning cycles / Less tedious daily routines.

HIGH THROUGHPUTAutomatic histoprocessing of batches with up to 210 standard cassettes; up to 270 with new turboflow thin cassettes.

QUALITYMorphological results equal to or better than conventional histoprocessing for H&E, HC, IHC, FISH.

FLEXIBILITYSIMULTANEOUS processing of different types of specimens. SIMULTANEOUS processing of specimens with different thickness.UNMATCHED throughput flexibility.

DELAYED START availabre for overnight processing.CONTINUOS ACCESS through elimination of cleaning cycles.

12-14 reagents

Overnight processing

Same-day processing

Hazardousreagents: xylene - formalin

FineFix, ethanol, isopropanol, JFC, ProWave

Same-day diagnosis

Diagnosis after48-72 hours

3-4 reagents only(2 step process possible)

Compassionate Technologyfor Same-Day Diagnosis and Improved Patient Care.CONVENTIONAL PATHOS

TIME TO IMPROVE

20 70 140 210 270

5

For the Grossing RoomOperator.

• Carry out grossing according to standard procedures.

• No need to standardize on 1.5/2.5 mm thickness specimens.

• Use formalin or Milestone’s FineFIX formalin-free fixative for enhanced molecular biologystudies.

For the Pathologist.• PATHOS processed slides enable the

pathologist to deliver same-day diagnosis of permanent slides with H&E and IHC staining* for more timely patient care.

• Same-day diagnosis will enhance the pathologist’s role in cancer patient management

• Less stress through more even work load.

For the LabAdministrator.• Same-day diagnosis, even for

afternoon specimens, for thereferring physician and patient.

• Improved service performance.• Improved work environment for

laboratory personnel.• Reduced cost for reagents

storage and disposal.

Benefits for the pat ie

* “Fast Track Biopsies (FTB): Description of a rapid Histology and Immunohistochemistry Method for Evaluation of Preoperative Breast Core Biopsies”Teresa Ragazzini, BSci, Elisabetta Magrini, BSci, Maria C. Cucchi, MD, Maria P. Foschini, MD and V. Eusebi, MD. Department of Oncology, Sections of Pathology and Oncologic Surgery,University of Bologna at Bellaria Hospital, Bologna, Italy International journal of surgical pathology 13 (3): 247-252, 2005

PATHOS

For the Histologist• Improved workload distribution.

Process as required for a more even workload distribution. PATHOS can the eliminate the need for night shifts.

• FlexibilityProcess 20-70-140-210 or any number as required.

• Economy.Process with three/four reagents only:1. formalin or FineFIX fixative.2. ethanol/isopropanol or ProWAVE or JFC solution.3. conventional grade wax.

• Easy sectioning.Even of difficult tissues (e.g. uterus).

6

For the Oncologistand Clinician

• Within hours oncologists and clinicians can advise patients on the base of definitive diagnosis.

• Treatment can be initiated immediately.

at ient and the patient care management team

For the HospitalAdministrator

• Reduced patient anxiety and stress by providing results within hours.

• Dramatic improvements in efficiency and laboratoryproductivity.

• Fast turn around to attract off site businnes.

For the patient.

• Elimination of needless anguish.• More timely start of

needed treatment.

7

Load rack with upto 210 cassettes.

Select a protocol.

Enter number of cassettes.

Press start That’s all.

What the user does....

PATHOS Designed w

1

2

3

4

8

What Pathos will do.....

Microwave

Microwave

VACUUM

VACUUM

Resistance heating

1 Lower the rack into the microwave cavity.

FIXATION-DEHYDRATION-CLEARING

2 Add formalin (FineFIX optional). F i xation is carried out at temperature and timeselected. Formalin is flushed out.

3 Run a rinsing step with ethanol.

4 Add ethanol to carry out microwave rapid dehydration of tissue. Ethanol is flushed out.

5 Add isopropanol. Clearing is carried out. When usingMilestone JFC solution or ProWAVE, steps 4-5 arereduced to one. When using FineFIX plus JFC-orProWAVE, step 2 is carried out with FineFIX and steps 3-4-5 are reduced to one.

EVAPORATION

6 Evaporate tissue’s excess solvents under vacuum.

TRANSFER

7 Transfer the “dry” rack to a resistance heated cavitywith paraffin at temperatures of 65–75°C.

IMPREGNATION

8 Carry out impregnation under presetvacuum/temperature conditions.

9 When the procedure is completed, an audible/visualalarm will notify the operator. For tissue preservation,the rack remains in the molten paraffin until amanual command is given.

UNLOAD/LOAD

10 The rack is unloaded for further processing. A new rack is loaded. A new rack can be loadedimmediately as no cleaning cycle is required forcontinuos access.

Extraction of lipids

Substitutionof water molecules withJFC/ProWAVE/Ethanol/Isopropanol

JFC/ProWAVE

Wax

d with the user in mind

1 5

6

8

MILESTONE CORE TECHNOLOGY

E u r o p ea n P a t e n t E P 0 8 2 2 4 0 3 - U S P a t e n t 6 , 0 4 2 , 874E u r o p ea n P a t e n t 16 0 5 2 4 3 - U S P a t e n t 7 , 0 7 5 , 0 4 5

JFC/ProWAVE/Ethanol/Isopropanoltraces

9

Open SystemNo captive reagentcommitments.Use of histologygrade wax.

Power failure back upbattery for specimen

protection.

Rack transfer device.

Work area totally enclosedduring operation.

Built-in charcoal/dust filterfor stand-alone operation.

High throughput, up to 270 cassettes.

Resistance heated paraffincavity. Eliminates need for

pumping wax (with potential blockage

problems) and eliminatescleaning cycles.

Large microwave processing cavity for fixation, dehydration,

clearing and evaporation steps.Continuous microwave

power output with invertertechnology.

Slide-out reagent drawerwith software controlled

transfer of processingreagents.

Engineered to Advance yourTissue Processing Capabilities for Same-Day Diagnosis.

User friendly,intuitivesoftware in an advancedtouch screenterminal.

US Patent 7,075,045

10

If the microwave reactor is the heart,then HistoEasy software is the brain.Intuitive, user-centric software.

• Simple customization of preset programs. • Fully automatic control of process parameters (temperature, time, agitation, vacuum, power).• Programmable “delayed start” time for pre-heating of wax.• Programmable “delayed start” time for after-hours operation.

Main startup screenDisplays the user’s favorite, most utilized programs ready forimmediate selection and start (up to 8 programs).

Reagent management system.Software controlled transfer of processing reagents – no manual

handling required.

Compliance with Quality Assurance procedures. • All steps of each program are documented to fulfill GLP, TQM, ISO

requirements.

• Full compliance to: CAP Guidelines - Advancing Excellence Commissionon Laboratory Accreditation Anatomic Pathology Checklist Revised:10/06/2005 and

• CLSI (formerly NCCLS) guidelines “Microwave Device Use in theHistology Laboratory; Approved Guideline” - GP28 – Vol. 25 No. 7, 2005.

PATHOS SOFTWARE.The essence of simplicity

Unique specimen protection features.• Password access to prevent unauthorized use/tampering on start-up of the system.• Over/under temperature threshold alert (up to ±5°C).• Over/under pressure threshold alert (up to ±50 mbar).• Protection of pre-installed programs.• Power Failure safety programs.

MILESTONE S.r.l.Via Fatebenefratelli 1/524010 Sorisole (BG) ItalyTel. +39-035-4128264Tel. +39-035-572735Fax +39-035-575498e-mail: medical@milestonesrl.comcustomersupport@milestonemedsrl.comwww.milestonemedsrl.com

MILESTONE MEDICAL25 Controls DriveShelton, CT 06484 - USATel: (203) 925-4240Toll-free: (866) 995-5300 Fax: (203) 925-4241e-mail: info@milestonemed.comwww.milestonemed.com

M I L E S T O N E

PATHOS/FO/REV 00/06

UNI EN ISO 9001: 2000 CERTIFIED

Technical Specifications

Specifications are subject to change without notice.

PATHOS When it Comes to Safety, We Think of Everything.

• Work area totally enclosed during operation.• Built-in vapor exhaust system for the entire work area.• Built-in charcoal/dust filter for stand-alone operation plus exhaust tube to external fume hood.• Transfer of cassette rack to and from processor enclosed module.• Safety interlock system shuts off rack transfer device whenever the safety window is raised, to prevent accidental injury• Audible alarms.

PATHOS - Fully Automatic Rapid Microwave HistoprocessingSystem for same-day processing/diagnosis P/N 62050.Complete system includes:A) PATHOS Microwave Unit - P/N 62000 Cabinet: All stainless steel heavy duty cabinet with coating resistant

to acid and organic solvents engineered for laboratory operation with built-in:

Microwave cavity. Paraffin cavity. Vacuum system. Compressor. Rack transfer system. Drawer for reagents with tanks. Built-in vapors exhaust with charcoal filter for cavities and

reagents compartments.Microwave cavity: All stainless steel. Power 0-850W ±10%, continuous power supply with inverter

technology, 1% power increments with microprocessor control. Level sensors for 1-2-3 levels of cassettes. MW leak sensor. Magnetic stirrer with speed control (200-600 RPM). Microprocessor control of vacuum up to 500mBar.Paraffin cavity: Power 800W , with resistance heating elements controlled by

PID technology. Optical sensors for min-max level and wax status. Magnetic stirrer with speed control (200-600 RPM). Microprocessor control of vacuum up to 100mBar.Reagents system: All stainless steel. Slide out drawer for easy access to load/unload reagents. Pneumatic valves for selection reagents with rapid transfer and

auto clean.

Touch control terminal: Windows C- E.Net operation system. 10.4" color touch screen 800x600 pixel, 256 colors. Milestone HistoEASY software, intuitive, user friendly. No external PC required for graphic display and save of T/T curve. Additional PC software for QC print out. Over 60 prestored and optimized programs for histoprocessing. USB, SERIAL RS232, PS2, PARALLEL output ports. Back-up information battery with auto-saving of specimens.

procedure in case of power black-out.

B) Starter Kit P/N 62400 including:- P/N 62300 Rack Transfer Kit (Qty 1)- P/N 62320 Rack Cleaning Container (Qty 1)- P/N 62200 Rack for 210 cassettes (Qty 2)- P/N 62212 Dust Filter (Qty 1)- P/N 62213 Carbon Filter (Qty 1)- P/N 62342 Allen Wrench 4 mm (Qty 1)- P/N 62337 Adjustable pin-type face spanner (Qty 1)

Power supply: 220V-50Hz.Dimensions: L 800 mm, D 1000 mm, H 2000 mm (31’’ x 40’’ x 79’’).Weight: 320 Kg - 705.45 lbs.

P/N 60250 Pathos Package for 230 Volt – 50HZ includes Pathosunit P/N 62000 + Starter Kit P/N 62400.

P/N 60270 Pathos Package for 230 Volt – 60HZ includes Pathosunit P/N 62020 + Starter Kit P/N 62400.

P/N 60260 Pathos Package for 115 Volt – 60HZ includes Pathosunit P/N 62010 + Starter Kit P/N 62400.