NGS solutions for research and clinical applications in ... · PDF fileNGS solutions for...
Transcript of NGS solutions for research and clinical applications in ... · PDF fileNGS solutions for...
1
The world leader in serving science
NGS solutions for research and
clinical applications in oncology
2
Routine Biomarker Analysis
• Limited sample volumes
• Multiple biomarkers for one disease indication
• Reflex testing is too slow
• Growing list of biomarkers changing rapidly
• Fixed assay needed for approval processes
Current methods to test samples against various
biomarkers are slow and often require more tumour
sample than available
Today’s Challenges
3
Ion Torrent™ Next-Generation Sequencing
• Detection of multiple biomarkers in one test from one sample, in
one streamlined workflow¹
• Accurate and reproducible detection of variants
• Hotspots, SNPs, indels, CNVs and gene fusions in a single
workflow for DNA & RNA
• Fast turn-around time
• From 10 ng of DNA or RNA from FFPE tissue
• Already implemented in clinical research and early development of
future targeted therapies2
• First CE IVD solution for routine diagnostics available
• Oncomine Solid Tumour DNA kit*
• Oncomine Solid Tumour Fusion Transcript kit*
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
4
Ion Torrent NGS Solutions
for Cancer Research
From Transcriptome
to Oncomine Assays
For Research Use Only. Not for use in diagnostic procedures.
5
Ion Torrent NGS panels for cancer research
• Ion AmpliSeq™ BRCA1 and BRCA2 Panel
• Ion AmpliSeq™ Colon and Lung Cancer Research
Panel v2
• Ion AmpliSeq™ RNA Fusion Lung Cancer Research
Panel
• Ion AmpliSeq™ Comprehensive Cancer Panel
• Ion AmpliSeq™ Cancer Hotspot Panel v2
• Ion AmpliSeq™ Transcriptome
• Oncomine™ Focus Assay
• Oncomine™ Comprehensive Assay
For research use only. Not for use for diagnostic procedures
6
Human Gene Expression with Ion AmpliSeq Transcriptome and Ion 540 Chip
For Research Use only. Not for use in diagnostic procedures.
Samples • Four resected invasive ductal breast carcinoma research samples
• Starting input 10ng of FFPE RNA
Optimum panel design & performance • >20,800 genes on Ion 540 Chip (8 barcoded samples per chip)
• 13,740 mean genes per sample detected
• >0.99 pairwise replicate correlation
• 0.984 gene count replicate correlation
High quality results • Top 50 most variable genes with differential expression show
clear clustering by sample type as well as by sub-ype
7
THE ONCOMINE™
KNOWLEDGEBASE
Pre-NGS sample prep:
• Custom / pre-designed
panels
• Hundreds of gene variants
per sample in single run
• Low input amounts
Ion AmpliSeq™
Technology*
One of the world’s largest curated cancer genomic database:
• Public sources
• Peer reviewed literature
• Published clinical research
trials
Compendia
Bioinformatics
Our Ion Torrent NGS Cancer Research Tools
*For Research Use Only. Not for use in diagnostic procedures.
Ion Torrent™ NGS platform:
• Minimal sample input
• Fast turnaround times
• Enables reproducible results
• Enables accurate performance
• All in a single run
Ion Torrent™
Systems*
8
Hotspot Mutations 8,000 exomes + COSMIC database
Hotspot enrichment analysis
Deleterious Mutations 8,000 exomes, COSMIC database
Indel + nonsense enrichment analysis
High-Level CNVs 30,000 array-based genomes
Minimal common region analysis
Gene Fusions 6,000 transcriptomes + COSMIC
Proprietary fusion analysis
One of he world’s largest curated cancer genomic database, gathered from
public sources, peer reviewed literature, and published clinical research trials
The Oncomine Knowledgebase
The Oncomine™
Knowledgebase
For Research Use Only. Not for use in diagnostic procedures.
9
Bladder
Breast
Colorectal
Endometrial
Esophageal
Gastric
GIST
Glioblastoma
Head and Neck
Kidney
Liver
Melanoma
Mesothelioma
NSCLC
Osteosarcoma
Ovarian
Pancreas
Prostate
Basal Cell
SCLC
Sarcoma
Testicular
Thyroid
Solid Tumor Driver Variant Map
Copy gain Copy loss Hotspot Deleterious Gene fusion Legend: 0.01 >0.30
ALK EGFR
KRAS
TP53 PIK3CA
ERBB2
NTRK1, RET, ROS1
BRAF
NRAS
KIT
CTNNB1
CCND1
MYC
10
Oncomine Assays: Solid Tumor Cancer Research NGS Assays Designed for Translational and Clinical Research
Benefits:
• Enables detection of relevant hotspots, SNVs, indels, CNVs and gene fusions in a
single workflow
• Intelligent NGS content design-based on the Oncomine Knowledgebase
• Minimal sample input required per run—making it well suited for analysis of
precious tumor samples
• Easy-to-perform workflow with fast turnaround time—get your NGS data
easily and quickly
• Service offerings to meet your clinical research needs
Detects variants in 52 solid tumor genes
that are associated with current
oncology drugs and backed by
published evidence
Detects variants in 143 unique genes
relevant to published trials
Oncomine™ Focus Assay: Oncomine™ Comprehensive Assay:
For Research Use Only. Not for use in diagnostic procedures.
11
Oncomine™ Focus Assay: Content Summary
Categorized by somatic alteration type
Hotspot genes
Focal CNV gains
Fusion drivers
Intelligent design includes hotspot SNV and indels, CNVs and gene fusions
52 genes
35
19
23
Categorized by potential relevance
Labels
Guidelines
Drug Targets
Clinical Trials
12
9
43
>400(US)
12
Run Sequence
Prepare Library
Sample Input
Analyze Data
Prepare Template
Oncomine Focus™ Assay Workflow
Oncomine
Focus™ Assay
FFPE material
including fine
needle aspirates,
needle biopsy
Oncomine™
Knowledgebase
Reporter
Ion Select™ 318
Chip
Ion OneTouch™
Select Template
200 Kit
Six samples, one run, to access hotspots, SNVs, indels,
CNVs and gene fusions for 52 solid tumor genes
*For Research Use Only. Not for use in diagnostic procedures.
13
Cohort analysis
• 127 FFPE tumor samples analyzed across 4 different
laboratories
• Demographics:
• Median age: 58 (range 18-86)
• Male 52%, Female 48%
• Ethnicity: 69% Asian, 29% Caucasian, 2% Unknown
• Sample characteristics:
• Tissue of origin: Lung 19%, Ovary 12%, Stomach 12%, Brain 11%,
Kidney 8%, Cervix 8%, Skin 8%, Esophagus 5%, Pancreas 4%, Uterus
4%, Colon 3%, Prostate 3%, Liver 3%
• Tumor grade:
• G1 3%, G2 30%, G3 15%, G4 52%
• Well-Differentiated 6%, Well to Moderate 9%, Moderately Differentiated 50%,
Moderate to Poor 20%, Poorly Differentiated 15%
14
Examples of Recurrent Somatic Mutations detected by Oncomine Focus
sample tissue hotspots CNVs fusions 1193124B Brain MET p.M1268T, IDH1 p.R132H CDK6, PDGFRA, KIT PTPRZ1-MET.P1M2
1199440B Brain EGFR p.A289T EGFR EGFR-EGFR.E1E8
1188945B Brain IDH1 p.R132H CDK4
1199191B Brain GOPC-ROS1.G8R35.COSF1139
1181647B Brain EGFR-EGFR.E1E8
1181219B Brain BRAF p.V600E
1181943B Brain IDH1 p.R132H
313774A1 Breast ERBB2 p.L755S, ERBB2 p.G776C, PIK3CA p.M1043V
308452A4 Breast PIK3CA p.E545K
1182647B Colon KRAS p.G12D, PIK3CA p.E545K
1185114B Colon KRAS p.G12D, PIK3CA p.E545K
1186528B Colon BRAF p.V600E
1187394B Lung MET p.T1010I, KRAS p.G12C
1200313B Lung CTNNB1 p.D32N, KRAS p.G12D
1194253B Lung PIK3CA p.E545K PIK3CA
1195523B Lung SDC4-ROS1.S2R32.COSF1265
1196001B Lung MET-MET.M13M15
1196650B Lung NRAS p.Q61L
1199311B Lung EGFR p.E746_A750del
1199087B Lung CCND1
1180121B Lung MYC
1196647B Lung PIK3CA
365 Skin NRAS p.Q61K, CTNNB1 p.G34R CCND1
367 Skin CDK4 p.R24C, BRAF p.V600E
370 Skin NRAS p.Q61K CCND1
364 Skin BRAF p.V600E
369 Skin BRAF p.V600E
366 Skin FGFR4
*For Research Use Only. Not for use in diagnostic procedures.
15
Oncomine™ Focus Assay: Reproducible Hotspot detection
Cancer type, sample, gene, variant
*For Research Use Only. Not for use in diagnostic procedures.
16
Cancer type, gene, variant
Oncomine™ Focus Assay: Reproducibility and consistency relative to Sanger
*For Research Use Only. Not for use in diagnostic procedures.
17
CNV detection by Oncomine™ Focus Assay*: Comparison to FISH
• 20 FFPE tumor samples
representing 8 different cancer
types
• Tumor fraction range 40-100%
• Validated FISH assays for 10
different gene targets
• Samples run at 4 different labs
from different sections of the
same block
• 97% sensitivity (67/69) to detect
CN ≥ 8; 94% (81/86) sensitivity to
detect CN ≥ 6 using the 5% CI ≥ 4
Good concordance between CN estimates produced by FISH or NGS
*For Research Use Only. Not for use in diagnostic procedures.
18
Gene Fusion detection by Oncomine™ Focus Assay*
• Targeted fusion breakpoint
assays
• Alignment of reads to
reference sequences
Sensitive and specific detection of fusion breakpoints *For Research Use Only. Not for use in diagnostic procedures.
EML4-ALK.
E6aA20.
AB374361
CCDC6-RET.
C1R12.
COSF1271
19
Oncomine™ Focus Assay: Gene Fusions
Driver Partner Gene Variants
(N)
ALK A2M, ACTG2, ATIC, C2orf44, CARS, CLIP4, CLTC, DCTN1, EML4, GTF2IRD1, HIP1, KIF5B, KLC1, MEMO1, NCOA1, PRKAR1A, PTPN3, RANBP2, SEC31A, SMEK2, STRN, TFG, TPM1, TPM3, TPM4, TPR, TRAF1, VCL
62
RET ACBD5, AFAP1, AKAP13, CCDC6, CUX1, ERC1, FKBP15, GOLGA5, HOOK3, KIAA1468, KIF5B, KTN1, NCOA4, PCM1, PRKAR1A, RUFY2, SPECC1L, TBL1XR1, TRIM24, TRIM27, TRIM33
41
ROS1 CCDC6, CD74, CEP85L, CLIP1, CLTC, ERC1, EZR, GOPC, HLA-A, KDELR2, KIAA1598, LRIG3, MSN, MYO5A, PPFIBP1, PWWP2A, SDC4, SLC34A2, TFG, TPM3, ZCCHC8
35
NTRK1 BCAN, CD74, CEL, DYNC2H1, IRF2BP2, LMNA, MPRIP, NFASC, RNF213, SQSTM1, SSBP2, TFG, TPM3, TPR 19
NTRK2 AFAP1, AGBL4, NACC2, QKI, SQSTM1, TRIM24, VCL 7
NTRK3 BTBD1, COX5A, ETV6 6
FGFR1 BAG4, ERLIN2, TACC1 4
FGFR2 AFF3, BICC1, CASP7, CCAR2, CIT, MGEA5, OFD1, SLC45A3, TACC3 10
FGFR3 AES, BAIAP2L1, ELAVL3, TACC3 26
BRAF AGTRAP, AKAP9, CDC27, FAM131B, FCHSD1, KIAA1549, PAPSS1, SLC45A3, SND1, TAX1BP1, TRIM24 15
MET BAIAP2L1, C8orf34, CAPZA2, OXR1, PTPRZ1, TFG, TPR, MET exon 14 deletion 10
other drivers: EGFR, ERG, ETV1, ETV4, ETV5, FGFR1, RAF1, PPARG, ABL1, AKT3, AXL, ERBB2, PDGFRA 36
total targeted assays 271
expression imbalance assays for ALK, RET, ROS1, NTRK1 8
expression controls 5
*For Research Use Only. Not for use in diagnostic procedures.
20
A targeted, multi-biomarker assay that enables detection of
variants in 52 genes relevant to solid tumors
Oncomine™ Focus Assay*
Intelligent NGS content design:
• Designed for translational & clinical research, includes 52
key cancer genes associated with current oncology drugs
and published evidence
• Includes relevant hotspots, SNVs, indels, CNVs and gene
fusions in a single workflow for DNA and RNA
• Content driven by the Oncomine™ Knowledgebase;
curated cancer genomics database
Sensitive tumor analysis:
• Enables detection using low input amounts including FFPE
fine needle aspirates and core needle biopsies
• Deliver results on more of your FFPE samples
*For Research Use Only. Not for use in diagnostic procedures.
21
Proposed Plans for IVD Product Development
Oncomine™ Focus
Assay* RUO
Early Development
Oncomine™ Universal
Dx Test IUO
Registration Trials
Oncomine™ Universal
Dx Test CE IVD
Companion Diagnostics
*For Research Use Only. Not for use in diagnostic procedures.
*The content provided herein may relate to products that have not been officially released and is subject to change without notice.
In cooperation with pharma Industry –
Validating the assay on clinical trial samples for
therapy selection (on PGMDx, as a full workflow )
2015 2016
22
Oncomine Comprehensive Assay* Content Summary
*For Research Use Only. Not for use in diagnostic procedures.
Categorized by somatic alteration type
Hotspot genes
Focal CNV gains
Full CDS for DEL
mutations & CNV loss
Fusion drivers
143 genes: Several used in multiple applications
(hotspot, CNV, driver fusion)
143 genes
73
49
26
22
Categorized by potential relevance
12
9
72
>450(US)
Labels
Guidelines
Drug Targets
Clinical Trials
23
NCI Match Trial
1Mickey Williams, PhD, Frederick National Laboratory for Cancer Research
Overview
Goals
Goals Approach
• Nationwide study open to
~2,400 NCTN sites
• 3-years, 3,000 samples
• Multiple clinical laboratories
sequencing tumor samples
• Multiple basket study design
• Overcome drug
development challenges
with clinical trial
enrollment & patient
matching
• Avoid undue costs & time–
to– enrollment process
• A clinical research study
using Ion Torrent™
instrumentation and
Oncomine® reagents
• NCI validation performed
in alignment with FDA
requirements for
investigational use1
24
Publication: Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors.
*For Research Use Only. Not for use in diagnostic procedures.
• Performance characterized with
molecular standards and > 300 FFPE
samples
• NGS results matched those of
validated single gene tests
• Additional relevant variants detected
• Results validate the multiplexed
PCR-based RNA-seq approach for
detecting targeted gene fusions
25
Oncomine™ Comprehensive
Assay*
Relative Performance
Gene Test Molecular Pathology Results Sensitivity Specificity
BRAF
V600 BRAF: 63 samples
• 29 positive (26 V600E, 2 T599dup, 1 V600K)
• 34 negative
• Melanoma, Colorectal adenocarcinoma, Lung
adenocarcinoma, Endometrial adenocarcinoma
100% (29/29)
100% (34/34)
EGFR
L858R &
Exon 19 del
EGFR: 22 samples • 3 positive (2 Exon 19 del, 1 L858R)
• 19 negative
• Lung adenocarcinoma, Sarcomatoid carcinoma
100% (3/3)
100% (19/19)
KRAS
G12, G13,
Q61
KRAS: 21 samples • 11 positive (1 G12A, 2 G12 D, 5 G12V, 2 G13D, 1 Q61K)
• 10 negative
• Colorectal adenocarcinoma, Small bowel adenocarcinoma
100% (11/11)
100% (10/10)
n=103
*For Research Use Only. Not for use in diagnostic procedures.
Comparison to Verified Single Gene Test Results
Hovelson et al., 2015. Development and validation of a scalable next-generation sequencing
system for assessing relevant somatic variants in solid tumors. Neoplasia 17:385-399.
26
Oncomine™
Knowledgebase
Reporter
Ion Reporter™
Workflow*
Lab Generated
Report*
Research
Laboratory
Oncomine Knowledgebase Reporter
*For Research Use Only. Not for use in diagnostic procedures.
Genetic variants
Associated published evidence
27
Relevant variants detected by the Oncomine™ Comprehensive Panel*
Tumor Sample Types Analyzed Using the Oncomine™ Comprehensive Panel*
*For Research Use Only. Not for use in diagnostic procedures. Hovelson et al., 2015. Development and validation of a scalable next-generation sequencing
system for assessing relevant somatic variants in solid tumors. Neoplasia 17:385-399.
28
Demonstration of the Oncomine Comprehensive Assay analyzed on the Ion S5 System
Samples used: Sample 1: 80 / 20 mix, AcroMetrix™ Oncology Hotspot Control (DNA) / Mixture of three
lung cancer cell lines (RNA)
Sample 2: 80 / 20 mix, CRL-1619 cell line (DNA) / Mixture of 3 lung tumor cell lines (RNA)
Sample 3: 80 / 20 mix, HCC1143D cell line (DNA) / normal colon cell line (RNA)
Reagents used: • Oncomine Comprehensive Assay Primers and Library Kit
• Ion S5 Series Template and Sequencing Reagents
Panel metrics • 143 gene targets (2,738 amplicons, 3 pools) to DNA & RNA (fusion transcripts)
• Run on an Ion 530 Chip (3 samples per chip)
Mutation Detection Results • Highly concordant results across Ion Torrent platforms
• Gene Fusions: 100% of fusions were detected
• SNVs: 99.6% of SNVs were detected
• No false positive SNV calls were generated
Note: Demonstration for feasibility and baseline performance only. Not a study for clinical validation.
For Research Use only. Not for use in diagnostic procedures.
29
Summary: Oncomine NGS Assays for Research
Utilize low sample input—enabling you
to access results for more of your samples
Intelligent NGS content design backed
by the Oncomine™ Knowledgebase and
confirmed with pharma partners
Single workflow to analyze 52 or 143
solid tumor genes for biomarker analysis
Designed to meet your needs for biomarker analysis
3-4 FFPE slides, compatible with fine
needle aspirates and core biopsies
For research use only. Not for use for diagnostic procedures
30
Oncomine Solid Tumor
Kits* for Clinical Diagnostics
Oncomine™ Solid Tumour DNA Kit*
Oncomine™ Solid Tumour Fusion*
Transcript Kit
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
31
Oncomine Solid Tumour Kits Offering
• RNA/DNA analysis in one workflow from sample to result typically
in one day
• Requires as little as 10 ng of DNA or RNA, which can be obtained
from as few as 1–2 FFPE slides
• Targeted approach allows accurate detection of relevant somatic
alterations in solid tumors with evidence linking alterations to targeted
therapies
• Designed in cooperation with group of leading cancer clinicians:
OncoNetwork
• CE-IVD* ready-to-use, flexible solution
• Manufactured under GMP and ISO 13485
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
32
Goal: Develop a complete solution for colon and lung cancer biomarker DNA and RNA
analysis that is efficient, not subjective, and works with limited FFPE samples
OncoNetwork Consortium Designed with input from a global team of leading cancer clinicians
Radboud University
Medical Center
Trinity College
ARUP Institute
Kinki
University
Viollier Université Paris
Descartes
Warwick
Medical
School
IPATIMUP
Portugal
Queen’s University
ARC-NET
University of
Verona
Centro Ricerche
Oncologiche
Customer Design Requirements
DNA Analysis RNA Analysis
Low input DNA requirement Reduced cost/complexity and good concordance with FISH
FFPE sample compatibility Quantitative, reliable results using low input of FFPE RNA
Selective gene content View multiple fusions simultaneously
Easy to implement Easy to interpret results without the need for a bioinformatician
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
33
96 test kit
Consists of 6 packs, 16 tests each
and it is possible to run 1–16
samples at once
Contains primers, library
reagents and equalizer
Manufactured according to GMP and ISO 13485 standards
High level of Quality Control helps provide confidence in
reproducibility, accuracy, and consistent quality of results
CE-IVD* Ready-to-Use Solution
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
In compliance with current
European In Vitro Diagnostic
Directive (IVDD)
Helps simplify in-house
validation for accreditation
purposes
34
Customer evaluation of the
Oncomine CE IVD Solid Tumour kits*
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
35
Multi-Centric Evaluation of the CE IVD kits in Spain
Aim of this study was to demonstrate the applicability of the Oncomine™ CE-IVD kits in
the clinical diagnostic routine of the pathology labs with the objective to reduce the time
for patient’s diagnosis, the hands-on work and increasing the results sensitivity
36
Multi-Centric Evaluation of the CE IVD kits in Spain
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
Study Design
Results
• 46 samples (lung and colon CA and melanoma)
• Provided by 8 laboratories running routine solid tumour biomarker testing
• 6 previously characterized (by FISH or PCR), anonymized FFPE samples from
each laboratory
• 2 for fusion transcript and 4 for gene mutation analysis
• 3 section of each samples were prepared and always one anlysed in 3 laboratories
• Hospital Ramon y Cajal – Madrid (not experienced in NGS)
• Hospital 12 de Octubre – Madrid (not experienced in NGS)
• Laboratorio de Dianas Terapeuticas – Madrid (experienced in NGS)
• Very strong inter-laboratory concordance of results obtained, with the reproducibility
between 96% and 100%
• All the expected variants (32) were identified and 23 potentially pathogenic extra
variants were found. With the DNA kit
• All fusion transcripts were detected with a very high sensitivity when sequencing
results reach the defined threshold of quality to be analysed. Just 1 false negative was
found.
• Using the kits in diagnostic routine increases laboratory productivity while achieving
quicker time to results and higher sensitivity
37
Multi-Centric Evaluation of the CE IVD kits in Spain
Inter-Laboratory Concordance
DNA mutation analysis RNA fusion transcript analysis
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
38
Accreditation of of NGS workflow for routine diagnosis Cochin Hospital, Paris, France
Aim of the study was evaluation of the performance of the Oncomine Solid
Tumour DNA kit* in order to prepare aaccreditation of NGS workflow for
routine diagnosis in melanoma according to ISO15189.
Study Design
• 163 analysis in 10 runs (8 or 16 samples on 316 or 318 chip)
• 2 runs with the same libraries (stored 4°C for 2 months or -20°C for one month)
• Materials:
• 15 IQC : commercial DNAs with known BRAF and NRAS genotypes (Horizon
Diagnostics (AmpliTech): FFPE DNAs
• 20 DNAs from inter-laboratory comparison testing (Dr. Hélène Blons, HEGP
Hospital, Paris)
• 1 negative extraction control (blank paraffin control block)
• 20 EEQ from external quality assessment (EQA)
• Parameters Evaluated:
• Repeatability and Reproducibility
• Inter-operator variability
• Analytical sensitivity and specificity
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
• Limit of detection
• Contamination
• Robustness
39
Accreditation of of NGS workflow for routine diagnosis Cochin Hospital, Paris, France
• The expected
performances of the Oncomine™ Solid Tumour DNA Kit have been experimentally confirmed in a routine diagnostic laboratory for hotspot mutation detection in melanoma.
• The same experiments will be used to extend the validation to hotspot mutation detection in lung and colon cancers.
Parameters
Repeatability √
Reproducibility √
Inter-operator variability √
Analytical sensitivity and specificity √
Limit of detection √
Contamination √
Robustness √
Conclusion
*CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).
40
Summary
Actionable, content-driven targeted NGS will transform
the future of cancer care
Thermo Fisher Scientific leads the way with the
market-leading targeted NGS solution for research and clinical
applications based on the Ion Torrent™ platforms
Ion S5™ System*
Ion Proton ™ System*
Ion PGM™ Dx System** with
combined function software Ion PGM™ System*
*
*For research use only. Not for use for diagnostic procedures
**CE marked and registered in accordance with in vitro Diagnostic Medical Devices Directive (98/79/EC).