GENReports: Market & Tech Analysis Mass Spectrometry ... · GENengnews.com...

GENReports: Market & Tech Analysis, Produced by Enal Razvi, Ph.D. © 2014 GENengnews.com

> Enal Razvi, Ph.D. Managing Director Select Biosciences, Inc. [email protected]

GENReports: Market & Tech Analysis

Mass Spectrometry: Front-end Sample Preparation and

Multiplexing


•  The focus of this GEN Market & Tech Analysis Report is our con@nuing coverage of the mass spectrometry space as its transla@ng from research to clinic

•  We have been following the mass spectrometry marketplace and based on our analyses have iden@fied technology trends and emerging themes –  In this report, we present here the various Front-‐end Sample

Prepara@on Companies with their Associated Offerings ! Focus here is on clinical transla@on of mass spectrometry towards diagnos@cs applica@ons

–  In this report we also document the Mul@plexed Mass Spectrometry in Development and present the various ongoing programs that have been disclosed

•  This report—the third in this series—seeks to frame therefore some of the ac@ve areas of inves@ga@on in this space which is undergoing a transla@on from research to clinic

Topic Introduc@on and Scope


Mass Spectrometry Market Segmenta@on and Evolu@on: Research to Clinic

1.   MS Market Segments are Presented as Relevant to the Clinical Diagnostics Space 2.   MS also Impacting Microbiology 3.   Not Much Impact in Cancer/Oncology Space ! Anecdotal Reports for Cancer Biomarker Studies 4.   Emerging Impact for Testing Proteins/Peptides ! Emerging Applications in Development 5.   Many LDTs and a Few IVDs based on Mass Spectrometry

Research Market [RUO]

Clinical Diagnos@cs Market Segments

Impacted by MS

Newborn Screening

Drugs of Abuse Tes@ng

[Downstream Assay]

Prenatal Tes@ng

Metabolite Tes@ng [AA, FA]

Steroids [Endocrine Disorders—a major driver], Vitamins

Microbiology


Companies Involved in Front-‐End Sample Prepara@on/Extrac@on, Standards, Reagents, I.

Manufacturer Instrument Name Technology Disease Area

Gerstel Gerstel Mul?purpose Sampler (MPS) Autosampler and Sample Prep Robot -‐ Use with standard GC/LC-‐MS systems

Automated SPE Supelco (Now Sigma) SPEware Solid Phase Extrac?on Columns Sample Prepara?on Materials

Deriva?zing Agents for GC/MS Specialized agents 30+ Deriva?zing agents for DOA tes?ng and confirma?on using GC-‐MS

Spark Holland Symbiosis Pico On-‐Line Extrac?on screening method (XLC-‐QqTOF) SPE system

Work with the Ins?tute of Toxicology in the BBGes in Germany for the detec?on of XenoBio?cs in Blood/Serum

Recipe ClinRep Diagnos?cs Complete HPLC Kits, reagents and accessories

Produce kits for Drugs of Abuse, Biogenic Amines, Metabolic Diseases, Oxida?ve Stress, Vitamin Status

ClinRep Therapeu?c Drug Monitoring Complete HPLC Kits

An?arrhythmics (Amiodarone in Plasma), An?asthma?cs (Theophylline, Theobromine and Caffeine), An?epilep?c Drugs (Lamotrogine, Suthiame, Leve?racetam), Immunosuppressants (Mycophenolic Acid), Pyschoac?ve Drugs (Atypical Neurolep?cs)

ClinTox Human Biomonitoring Complete HPLC Kits Kits for Benzene and Deriva?ves, Polycyclic Aroma?c Hydrocarbons

ClinTest, ClinCal, ClinChek Standards, Test solu?ons, Calibrators and Controls

ClinMass LC-‐MS/MS Kits LC-‐MS/MS Kits

Alcholism (Ethylglucuronide and Ethylsulfate), Immunosupressants (Cyclosporine A, Tacrolimus, Sirolimus and Everolimus), Psychoac?ve Drugs (Benzodiazepines), Vitamin-‐Status (Methylmalonic Acid, 250OH Vitamin D2/D3) Metabolic Diseases (Homocysteine) Nico?ne and Metabolites (Nico?ne and Metabolites)

ClinMass Op?misa?on Mixes CE Marked products are available ClinMass Internal Standards



Phenomenex Kinetex Columns Core Shell Columns

Used for Vitamin Analysis ( 3-‐epi-‐25-‐OH-‐Vitamin D3 and 25-‐OH-‐Vitamin D3), Vitamin B6, Underiva?zed Methylmalonic Acid

Aldosterone, Catecholamines, Estrogens, Insulin, Steroids Panel, Total Testosterone

Strata™-‐X-‐Drug B Tubes Solid Phase Extrac?on Sorbent

Drugs of abuse tes?ng panels, Pain Panel, Amphetamines, Barbiturates, Benzodiazepines, Cocaine, Methadone, Opiates, Phencyclidine, Propoxyphene, Tetrahydrocannabinol (THC), Extended Pain Panel

Strata™-‐X SPE Cartridges and Kinetex® Core Shell HPLC and UHPLC Columns Digitoxin, Digoxin, Gabapen?n and pain panels

Imtakt USA Scherzo Columns Chromatography columns for most applica?ons

Indigo Biosystems Automated Data Analysis & Review for LC-‐MS

Informa?cs company specializing in Mass Spec Diagnos?c labs

Provides algorithmic checking service that highlights results that need to be checked by a human eye 'Review by Excep?on'

GL Sciences Inert range of Columns Biotage Solute SPE Detec?on of synthe?c Cannabinoids Evolute Columns Supported Liquid Extrac?on (SLE) Removal of Phospholipids to solve quan?ta?on issues,

Cerilliant Standards for Clinical Research Provide Internal Tes?ng Standards for Clinical LC-‐MS/MS Tes?ng

Biocrates MetaDisIDQ Kit

Measurement of up to 181 metabolites, selected for use in research studies of a wide range of metabolic diseases: Acylcarni?nes, Amino Acids, Biogenic Amines, Hexoses (sum of Hexoses), Phospho-‐ and Sphingolipids, Phospha?dylcholines, Lyso-‐Phospha?dylcholines, Sphingomyelins

Absolute IDQ Steroid Reagents Absolute IDQ Kits Life Technologies/Thermo Invitrosol LC/MS Protein Solubilizer Kit LC/MS BSA Tryp?c Digest

Companies Involved in Front-‐End Sample Prepara@on/Extrac@on, Standards, Reagents, II.



Thermo Fisher Scien?fic

Amine-‐reac?ve Thermo Scien?fic TMT* Isobaric Mass Tagging Kits and Reagents

Tandem Mass Spectrometry, Protein labelling and quan?ta?on

Protein iden?fica?on and quan?ta?on from mul?ple samples of cells, ?ssue or biological fluids, Protein expression profiling of normal vs. disease states or control vs. treated, Mul?plex up to six different samples concurrently in a single experiment, Quan?ta?ve analysis of proteins for which no an?bodies are available, Iden?fica?on and quan?ta?on of membrane and post-‐transla?onally modified proteins, Iden?fica?on and quan?fica?on of hundreds to thousands of proteins in a single experiment

AB Sciex Standards & Reagents Amplifex Diene Reagents Vitamin D3 and D2 enrichment

Amplifex Keto Reagents aTRAQ Kits for Amino Acid Analysis in Hydrolysates aTRAQ Kits for Amino Acid Analysis in Physiological Fluids

Bio-‐Rad ProteinChip SEND (surface-‐enhanced neat desorp?on) ID array

Companies Involved in Front-‐End Sample Prepara@on/Extrac@on, Standards, Reagents, III.


Mul@plexed Mass Spectrometry in Development, I. Department.

Ins@tu@on, Company Disease Area Interrogated MS Technology Deployed ASRs Addressed/Addi@onal Informa@on

Thermo Fisher Scien?fic Alzheimer’s Disease Mass Spectrometric Immunoassay (SRM assays)

Quan?fica?on of CP, ApoE monitoring and isoform-‐ specific pep?des and several Aβ pep?des.

Mount Sinai Hospital Male Infer?lity Diagnosis

Seminal Plasma mass spectrometry and mul?plex selected reac?on monitoring (SRM) assays

Detec?on of Proteomic Biomarkers (TEX101 & ECM1) to diagnose male infer?lity and remove the need for Tes?cular Biopsy

Columbia University Pathogen Discovery and Molecular Diagnos?c MassTag-‐PCR

MassTag PCR is a mul?plex PCR assay that uses a library of>60 dis?nct low molecular mass tags to code for microbial gene targets by conjuga?ng each primer species with a dis?nct mass tag via a photocleavageble linkage. Aoer PCR amplifica?on, separa?on of amplifica?on products from unincorporated primers and release of mass tags from the amplifica?on products by UV irradia?on, tag iden?ty is analyzed by mass spectrometry

bioMerieux

Rapid screening of an?bio?c resistance mechanisms and virulence factors LC-‐ESI-‐QqQ in SRM

Mul?plexed detec?on of 124 pep?des from 17 staphylococcal proteins

Johns Hopkins University School of Medicine

Monitoring of Pain Management drugs HPLC-‐MS/MS

Using HRAM as a qualita?ve method for screening 46 pain management and illicit substances in Urine

Ibis Biosciences Iden?fica?on of Fungal Pathogens PCR/ESI-‐MS

Detec?on and iden?fica?on of fungal pathogens from BAL specimens


Department. Ins@tu@on, Company

Disease Area Interrogated MS Technology Deployed ASRs Addressed/Addi@onal Informa@on

Sequenom Center for Molecular Medicine Cys?c Fibrosis Screening Panel PCR and Assay SBE -‐ MALDI-‐TOF MS

Cys?c fibrosis transmembrane regulator (CFTR) muta?on screening via the development of a 108-‐member (muta?ons plus variants) panel

University of Vermont Bacterial Lung Infec?ons (In Development)

SESI-‐MS (Secondary Electrospray Ioniza?on Mass Spectrometry

Breath Analysis for the following bacterial pathogens -‐ H. influenzae, K. pneumoniae, L. pneumophila, M. catarrhalis, P. aeruginosa, S. aureus, and S. Pneumoniae

Washington University Urinary Pathogen Detec?on MALDI TOF -‐ MS Culture independant analysis of urine specimens for pathogen detec?on

AB Sciex & ISB in Searle P4 Medicine Data Independant Mass Spectrometry Tech

Massively mul?plexing -‐ Swath Analysis -‐ Quan?fica?on of almost all detectable proteins and pep?des in a complex sample in a single analysis

Sequenom Pneumonia and o??s media MALDI-‐TOF MS MLST (mul?locus sequence typing)

PCR amplicons were subjected to in vitro transcrip?on and base-‐specific cleavage, followed by analysis of the resultant fragments by using matrix-‐assisted laser desorp?on ioniza?on ?me-‐of-‐flight mass spectrometry (MALDI-‐TOF MS). Comparison of the cleavage fragment peak parerns to a reference sequence set permired automated iden?fica?on of alleles. 29 isolates of S. pneumoniae

Swedish Na?onal Biobank Qualita?ve mul?plex detec?on of all HHVs (Human Herpes Virus) MALDI-‐TOF MS

Currently using archival samples but could move into clnical diagnos?cs

Transla?onal Genomics Research Ins?tute, Phoenix Mul?plex SNP genotyping

Locus-‐specific PCR amplifica?on of genomic DNA, followed by shrimp alkaline phosphatase treatment to inac?vate unincorporated nucleo?des, single-‐base primer extension using mass-‐modified terminators, and MALDI-‐TOF MS for allele-‐specific detec?on

This protocol u?lizes proprietary enzymes, sooware and SpectroCHIP® Arrays that are pre-‐spored with a MALDI matrix

Mul@plexed Mass Spectrometry in Development, II.



Disease Area Interrogated

MS Technology Deployed

ASRs Addressed/Addi@onal Informa@on

Sequenom (Feb 2013 in development)

High-‐throughput single nucleo?de polymorphism-‐based typing of shared Pseudomonas aeruginosa strains in cys?c fibrosis pa?ents

iPLEX matrix-‐assisted laser desorp?on ionisa?on with ?me-‐of-‐flight mass spectrometry (MALDI-‐TOF MS)

The isolates were tested using a P. aeruginosa Sequenom iPLEX MALDI-‐TOF (PA iPLEX) method comprising two mul?plex reac?ons, a 13-‐plex and an 8-‐plex, to characterise 20 SNPs from P. aeruginosa house-‐keeping genes acsA, aroE, guaA, mutL, nuoD, ppsA, and trpE.

University of Texas Medical Branch (Published Protocol)

Monitoring the Innate Immune System

Quan?ta?ve 10-‐plex stable isotope dilu?on (SID)-‐selected reac?on monitoring (SRM)-‐MS assay

Department of Analy?cal Chemistry, University of Stockholm

High-‐Throughput Assay of 9 Lysosomal Enzymes for Newborn Screening.

Assay 9 lysosomal enzymes using 1 or 2 reac?on buffers using HPLC-‐MS/MS

University of Washington

Mul?plex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-‐Pick A/B and Pompe diseases Tandem mass spectrometry

Recently won the Gustavus John Esselen Award for Chemistry

Thermo Fisher Scien?fic

Heart disease, Stroke, Alzheimers, diabetes and metabolic syndrome

SRM MS mul?plexed assay for an apolipoprotein (Apo) panel

Apolipoprotein H precursor, apolipoprotein B precursor, apolipoprotein A-‐I preproprotein, apolipoprotein C-‐III precursor, apolipoprotein C-‐I precursor, apolipoprotein D precursor, apolipoprotein A-‐II preproprotein, apolipoprotein A-‐IV precursor and apolipoprotein C-‐II precursor

Mul@plexed Mass Spectrometry in Development, III.



Disease Area Interrogated

MS Technology Deployed

ASRs Addressed/Addi@onal Informa@on

Hôpital Cochin, Paris, France in conjunc?on with Perkin Elmer Diagnosis of adrenal disorders

Tandem MS/MS: Aoer liquid chromatography of serum extracts, steroids were quan?fied on Waters QuarroPremier mass-‐spectrometer by either targe?ng several informa?ve steroids for the diagnosis of congenital adrenal hyperplasia (CAH), or by establishing a complete steroid profile using the mul?steroid-‐CHS-‐kit from PerkinElmer.

Panel can screen for glucocor?coids, mineralocor?coids, and androgens

Division of Clinical Pharmacology, Department of Medicine, Lausanne, Switzerland

Therapeu?c Drug Monitoring -‐ An? Fungal Therapies

Mul?plex Ultra-‐Performance Liquid Chromatography-‐Tandem Mass Spectrometry Method

Simultaneous Quan?fica?on in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole-‐N-‐Oxide, Anidulafungin, and Caspofungin

Muta?ons amenable to drug targe?ng present in urothelial, colorectal, endometrioid, and thyroid carcinomas and in melanoma

Mul?plexed assay panel with mass spectrometry–based analysis to detect 390 muta?ons across 30 cancer genes

Genes most frequently mutated across mul?ple cancer types were BRAF, PIK3CA, KRAS, and NRAS

Mul@plexed Mass Spectrometry in Development, IV.


In Summary

•  This GEN Report provides a snapshot of the qualita@ve trends in the mass spectrometry space—focusing on the technology trends in the front-‐end sample prepara@on arena

•  We also provide here a snapshot of the mul@plexed mass spectrometry space as its relates to the deployment of mass spectrometry towards clinical diagnos@cs [with a perspec@ve towards the disease areas addressed]

•  This report—the 3rd in this series focused on mass spectrometry—seeks to document the transla@on of this plaYorm towards clinical applica@on in the broader diagnos@cs space

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