Sample Prep, Assay Development and Validation

Developing a highly sensitive, reproducible and robust molecular assay may be a challenge regardless of whether it is an IVD or an LDT assay. Novel sample preparation technologies significantly increase sensitivity and specificity of a test that is run on a heterogeneous sample or a sample that contains a low concentration of analyte. Rapid sample-to-result technologies help cut down turnaround time while decreasing the cost of a test. Cambridge Healthtech Institute’s Fifth Annual Sample Prep, Assay Development, and Validation conference is designed to bring together leading industry and academia experts in biospecimen science and molecular diagnostics to discuss major challenges and latest advances in sample preparation for advanced molecular diagnostics technologies as well as development and validation of NGS and other advanced diagnostics assays.

Monday, February 12

10:30 am Conference Program Registration Open


11:50 Chairperson’s Opening Remarks

Karl V. Voelkerding, M.D., Professor of Pathology, University of Utah School of Medicine

12:00 pm Enabling More Complete Characterization of Genomic Variation with Linked-Read Sequencing

Sarah Garcia, Ph.D., Applications Scientist, Cancer and Inherited Disease Program Lead, 10x Genomics, Inc.

Current short-read (SR) NGS technologies fail to fully characterize individual genomes. 10x Genomics Linked-Reads (LR) preserve the advantages of short reads while enabling a more complete characterization of the genome. LR sequencing allows for identification of a wider variety of variants, reconstruction of haplotypes, and access to repetitive sequences. Disease-causing variation in samples with variants undetectable by standard SRs can be detected with LRs.

12:20 Tricks and Improvements to Library Preparation Techniques to Address Current Challenges

Robert Daber, Ph.D., Founder and CEO, Gnosity Consults

Next Generation Sequencing has tremendous potential for disrupting routine clinical practice in many areas of medicine. As many health care practices look to build precision medicine programs, access to clinical NGS testing for every patient is currently limited by several challenges. Here we will discuss several technical and biological challenges to library preparation and explore options for overcoming those shortcomings.

12:40 Immune Profiling by NGS: a Validated Multi-Biomarker Assay

Jeffrey Conroy, Senior Vice President of Technology Development, R&D, OmniSeq, Inc.

Given the ever-increasing number of combinatorial immunotherapeutic regimens tested in clinical trials today, the selection of combination partners is often not rationally guided. There is a need to accurately measure the multitude of molecular biomarkers that exist in the tumor microenvironment to assist with clinical decision making in this era of checkpoint blockade and cancer immunotherapy. The talk describes the validation of a NY state approved NGS assay that detects several known markers of the host anticancer immune response. The assay is robust, sensitive, reproducible, and to our knowledge is the first NGS assay for immuno-oncology that has been analytically validated for both RNA- and DNA-seq from a single FFPE biopsy specimen.

1:00 Session Break

1:10 Luncheon Presentation I: Leveraging Archival Tissues to Assess Transcriptional Changes in Sarcoma Patient-Derived Xenografts

Chensheng Willa Zhou, Principal Research Technician, Medical Oncology, Dana Farber Cancer Institute

Leiomyosarcoma (LMS) is a type of uterine sarcoma which is poorly understood, where available treatment options are very limited. In this study, we compared the whole transcriptome from formalin-fixed paraffin-embedded specimens of primary tumors and subsequent passages of PDX models developed by DFCI investigators with a view to conducting future preclinical studies in vivo.

1:40 Luncheon Presentation II (Sponsorship Opportunity Available)  

2:10 Session Break


2:30 Chairperson’s Remarks

David Wong, Professor & Associate Dean of Research, Dentistry, University of California, Los Angeles

2:40 Analytical Validation of a Liquid Biopsy NGS Assay

Lin Wu, Ph.D., Vice President, Development, Roche Sequencing Solutions, Inc.

This presentation will focus on important issues of analytical validation of NGS assays. Both IVDs and LDTs strategies will be covered. In this talk we will share the Roche Sequencing Solutions best practices and approaches that allow us to bring highly sensitive and robust assays onto the market.

3:10 EFIRM Liquid Biopsy (eLB)

David Wong, Professor & Associate Dean of Research, Dentistry, University of California, Los Angeles

Electric Field Induced Release and Measurement (EFIRM)- Liquid Biopsy (eLB) provides the most accurate targeted detection for non-small cell lung cancer (NSCLC). eLB requires only 40 µl of sample volume, no sample processing, reaction time is 15 min and can be performed at the point-of-care or high throughput reference lab using plasma or saliva. eLB detects actionable EGFR mutations in NSCLC patients with >95% concordance with biopsy-based genotyping.

3:40 Cell-Free DNA Genotyping in CLIA Environment: Pre-Analytical and Analytical Considerations

Raja Luthra, Ph.D., Professor, Hematopathology, The University of Texas MD Anderson Cancer Center

Circulating cell-free DNA (cfDNA) genotyping to detect tumor associated molecular aberrations has shown great promise as a minimally invasive alternative to tissue based genotyping. However, implementation of cfDNA genotyping for patient care has been slow due to lack of robust pre-analytical and analytical validation studies. This talk addresses potential challenges in implementation of cfDNA mutation testing using NGS and digital PCR platforms in clinical laboratory set up.

4:10 Chocolate Covered Strawberries and Human Biosamples

Jon Wetzel, COO, TriMetis Life Sciences
You spend $1000’s in reagents and time testing a sample just to find out that it’s not going to work for your project. How to define your sample needs to your supplier so you can receive the perfect specimens for your research project saving you time, money and aggravation.

4:25 Multiplex Mutation Analysis for Cancer Management by πCode Technology

Stuart Palmer, Ph.D., COO, Administration, PlexBio Co., Ltd.

PlexBio has developed a platform for high complexity mutation analysis. The IntelliPlex™ Lung Cancer Panel assesses the status of 58 somatic mutations and gene re-arrangements in liquid biopsy samples. The test offers a rapid, comprehensive and cost-effective way to interrogate patient samples with achievement of sensitivities of 0.01%-0.1%.

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)


Precision for Medicine

 6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


10:05 Chairperson’s Remarks

Hyungsoon Im, Ph.D., Assistant Professor, Center for Systems Biology, Massachusetts General Hospital

10:15 Technologies for Biosensing and Precision Health

Ronald W. Davis, Ph.D., Director of the Stanford Genome Technology Center, Professor of Biochemistry and of Genetics, Department of Biochemistry, Department of Genetics, Stanford School of Medicine

Breakthroughs in biomedical research are driven by technological developments. Our mission at the Stanford Genome Technology Center is to develop technologies that increase the speed, precision, and cost-effectiveness of genomic analyses and healthcare. Many of our technologies are based on direct electrical detection of molecular and cellular phenomena. We also integrate these technologies in precision health approaches to studying complex diseases including cancer, cardiovascular disease, and chronic fatigue syndrome.

10:45 Automated On-Chip Isolation of Circulating Biomarkers from Non-Invasive Liquid Biopsies

Joshua Smith, Ph.D., Research Staff Member, Translational Systems Biology and Nanobiotechnology, IBM T.J. Watson Research Center

On-chip separation technologies capable of isolating nanoscale biocolloids may be a game changer for personalized medicine and POC diagnostics. We have demonstrated that nanoscale deterministic lateral displacement (nanoDLD) can separate particles, such as exosomes, down to 20nm in size and nucleic acids as small as 100bp. In this talk, I will discuss how we’ve refined this continuous flow technology to isolate exosomes from patient urine samples for prostate cancer analysis.

11:15 Nano-Plasmonic Sensing Technology for Tumor-Derived Exosome Detection

Hyungsoon Im, Ph.D., Assistant Professor, Center for Systems Biology, Massachusetts General Hospital

This presentation will review a recent progress of nPLEX (nano-plasmonic exosome) technology. The sensor is based on transmission surface plasmon resonance (SPR) through periodic nanohole arrays. Target-specific exosome binding to the array via affinity ligands causes SPR signal changes, which enables sensitive and fast detection of exosomes. We applied the nPLEX system to detect exosomes collected from ovarian and pancreatic cancer patients.

Sensecare Medicals11:45 A One-Step, Highly Efficient Sample Prep Method from FFPE and Rare Precious Specimens for NGS and Real-Time PCR

Wen Huang, Ph.D., Scientist, SenseCare Medicals, Inc
Tom Xu, Ph.D., President, SenseCare Medicals, Inc

Limited quantity and poor quality of DNA and RNA obtained from FFPE or other rarely available specimens are major hurdles to the success of NGS and qPCR for Cancer research and clinical diagnosis. We have developed a very simple but highly efficient technology to solve this problem.

12:15 pm Session Break

12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


2:00 Chairperson’s Remarks

Christoph Borchers, Ph.D., Professor, Director, University of Victoria Genome British Columbia Proteomics Centre

2:10 Quantitation of Cancer Related Proteins in Tumors by iMALDI

Christoph Borchers, Director, University of Victoria Genome British Columbia Proteomics Centre

Immuno-matrix assisted laser desorption/ionization (iMALDI) assays allow highly sensitive and specific quantitation of target proteins on the peptide level by combining affinity-enrichment of endogenous and heavy labeled target peptides, followed by mass spectrometry analysis. We have successfully applied this technique to the analysis of the cancer-related proteins AKT1, AKT2, PI3K and PTEN from cancer cell lines, as well as AKT1 and AKT2 from fresh frozen and FFPE tumor tissues.

2:40 Towards Standardized, Routine Non-Targeted Metabolomics for Precision Medicine

Megan Showalter, Ph.D., Postdoctoral Scholar, West Coast Metabolomics Center, University of California, Davis

At the NIH West Coast Metabolomics Center, we use 17 mass spectrometers in the central facility for providing data, informatics services and collaborative research for over 400 projects and more than 25,000 samples per year. We will present cheminformatics workflows and example projects from cardiovascular health, type 1 and type 2 diabetes and cancer metabolism to showcase the usability that metabolomics has achieved in the past 20 years.

3:10 Mobilizing Medicine: Protein Pathological Surveillance

Jennifer Van Eyk, Ph.D., Director, Advanced Clinical Biosystems Institute in the Department of Biomedical Sciences, Director, Basic Science Research in the Women’s Heart Center, Erika J. Glazer Chair in Women’s Heart Health, Cedars-Sinai

Precision medicine requires biomarkers that are specific and responsive to an individual’s disease status. We hypothesize that proteins provide the specificity required to differentiate the dynamic and complex pathological differences between individuals over their lifetime. We have combined remote sampling devices that collect blood from anyone, anywhere and anytime with a 72 protein-multiplex assay representing 8 pathological signatures. Collectively, this provides clinical chemistry-grade surveillance over one’s lifetime.

3:40Redefining Protein Biomarkers – Structure vs. Expression

Arnon Chait, Ph.D., President and CEO, Cleveland Diagnostics

Protein biomarkers have been the workhorse of clinical diagnostics for virtually all medical indications – except for cancer. The dismal performance of such biomarkers in cancer could be related to their non-specific definition based on concentration in circulating fluids. Here we present a technology to redefine protein biomarkers based on cancer-specific changes to their structure. The technology is simple, low-cost, fits within the conventional clinical lab workflow, and has recently demonstrated superior clinical performance in prostate cancer directly against the same biomarker defined by serum concentration. Overview of the technology, results from a multicenter clinical study and future plans in breast and other cancers will be provided, and general comparison of cost/performance against imaging and circulating tumor cells and free DNA will be discussed.

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

The Challenge of Implementing Proteomics in Clinical Set Up

Christoph Borchers, Ph.D., Professor, Director, University of Victoria Genome British Columbia Proteomics Centre

  • How to improve the training for clinical proteomics?
  • Is there demand for proteomics kits? If yes, for which application?
  • Is there a demand for ring studies in clinical proteomics? If yes, who could organize a study?

Lessons Learned: What I Wish I Had Known Before I Started Validation

Jason N. Rosenbaum, MD, Assistant Professor, Pathology and Laboratory Medicine, University of Pennsylvania

Jennifer J.D. Morrissette, Ph.D., FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

Martin Siaw, Ph.D., MB(ASCP), Technical Consultant, Siaw Consulting

  • Selection of validation samples
  • Comparison to orthogonal assays
  • New CAP/AMP Guidelines
  • RNAseq in the clinical laboratory

6:00 Close of Day

Wednesday, February 14

7:00 am Breakfast Presentation (Sponsorship Opportunity Available)  

7:30 Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


10:50 Chairperson’s Remarks

Jennifer J.D. Morrissette, Ph.D., FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

11:00 Merging NGS Assays for Maximizing the Interrogation of Genomic Variants

Helen Fernandes, Ph.D., Associate Professor, Personalized Genomics Laboratory, Department of Pathology & Cell Biology, Columbia University Medical Center

Clinical laboratories use NGS assays for oncology that range from small to large targeted panels, to whole exome and transcriptome. Each assay has its advantages and limitations for the interrogation of relevant genomic variants. Concurrent sequencing of DNA based targeted NGS assays and RNA based assay for identification of fusions, are currently used in some laboratories. For the most part these integrated assays use the same chemistry with similar reagents. In this presentation, we will examine the merging of two assays with different chemistries for the concurrent identification of SNV’s, Indels and fusions from a single specimen. The validation, implementation and advantages of such applications will be discussed.

11:30 Getting the Most Out of the Least: Validation and Mutation Detection in Small and Degraded Specimens

Jennifer J.D. Morrissette, Ph.D., FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

Most next generation sequencing (NGS)-based clinical oncological testing has focused on sequencing all or most of the exons of clinically-relevant genes, which requires high DNA input and/or high quality DNA. Our academic laboratory receives tumor and specimen types for testing, some of which have insufficient amplifiable DNA for our larger 158 gene assay, either due to low quantity or poor quality. This talk will discuss the validation and clinical implementation of a two NGS panels for solid tumor specimens, with a large panel that covers over 150 genes and 750KB, and a small panel that captures hotspot amplicons and tumor suppressor exons, while requiring <1ng of input DNA. We have found that by providing a large panel for all tumor types, while offering an extremely targeted panel for specimens insufficient to run on larger panels, has expanded the application for NGS testing to include reflex testing of FFPE specimens with low DNA quantity or quality that fail QC for larger panels, small cytology specimens and other limited specimens.

12:00 pm Impact of Preanalytical Variables on Tissues by Studying Global Protein and Gene Expression: Implications for Use in Clinical Research

Lokesh Agrawal, Ph.D., Program Director, Biorepositories and Biospecimen Research Branch (BBRB), Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute

Clinically relevant proteomic biomarkers obtained from tissues promise to revolutionize cancer diagnosis and therapy. Several preanalytical factors have been shown to influence qualification and validation of these biomarkers. The talk will focus on biospecimen science issues and their standardization for assessing clinical biomarkers including validating upcoming immunotherapy markers. The talk will discuss the need to understand and standardize collection, processing, and storage procedures and develop quality control tools in order to minimize variations observed in biospecimens when assessing these biomarkers. This may also inform the future development of biomarkers and assist in the development and validation of diagnostic tests.

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing


1:50 Chairperson’s Remarks

Kai Wang, Ph.D., Principal Scientist, Institute for Systems Biology

2:00 Tissue Histopathology Investigations in Support of Clinical Trials for Novel Therapeutics: Considerations and Perspectives

Keith Wharton, M.D., Ph.D., Senior Medical Director, Leica Biosystems

Tissue histopathology investigations are central to discovery and preclinical development of novel therapeutics and for routine medical care, but their variable use in clinical trials represents a missed opportunity to improve our understanding of disease and the effects of various therapies on disease. I present major considerations and propose a question-based framework for implementation of tissue histopathology biomarker investigations in clinical trials, including several examples

2:30 Development and Clinical Validation of Large-Scale NGS Oncology Panels for Detection of SNVs, Indels, Fusion Genes and CNVs

Jeremy Segal, M.D., Ph.D., Director, Genomic and Molecular Pathology, Pathology, University of Chicago

More than ever, oncology genomics laboratories are under pressure to deliver more results at less cost and in less time using smaller and smaller specimens. Careful laboratory planning and a high level of technical proficiency are necessary to successfully navigate this environment, with a strong emphasis on creating individual assays that can deliver comprehensive genetic information about specimens, including SNVs, indels, fusion genes, CNVs and more. This session will provide strategies, examples and lessons learned during the process of creating and validating a large-scale hybrid capture cancer profiling assay at University of Chicago.

3:00 Turning Lead to Gold: Validating the Detection of Fusion Transcripts against an Imperfect Standard

Jason N. Rosenbaum, M.D., Assistant Professor, Pathology and Laboratory Medicine, University of Pennsylvania

Many therapeutic targets for cancer are fusion transcripts not easily multiplexed in traditional assays, such as fluorescent in situ hybridization (FISH). RNA-based next-generation sequencing (NGS) offers multiplexed detection and more detailed genomic information, offering significant advantages over FISH. Moreover, despite operating as a de facto “gold-standard,” FISH has a significant false-positive rate. We present our experience validating a clinical RNA-NGS assay against imperfect “gold-standards.”

3:30 Session Break


3:40 Chairperson’s Remarks

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania

3:45 Changes in Circulating Leukocyte Quantities Inform Dosing Decisions and Pharmacodynamic Effects in Combination Trials of Immune Oncology Therapeutics

Nathan Standifer, Ph.D., Senior Scientist, Clinical Pharmacology and DMPK, MedImmune

Immune oncology (IO) therapeutics are designed to activate exhausted T cells, thereby enhancing tumor-specific immune responses. While IO compounds have demonstrated substantial efficacy, most treated patients fail to respond. As such, trials of IO therapeutics combined with small molecule inhibitors have been undertaken. This presentation will describe the use of flow cytometry-based assays to monitor circulating leukocyte populations to characterize pharmacodynamic effects and inform dosing decisions in such combination trials.

4:15 Beyond Uni-Variate Analyses Using Cytometry Data - Translation into Clinical Space

Iulian Pruteanu-Malinici, Ph.D., Biostatistics, Investigator II/Lab Head at Novartis

Institutes for BioMedical Research (NIBR)

Here, we present a flow cytometry based framework that, when combined with state of the art bioinformatics, enables for the discovery of biomarkers that predict clinical response of CTL019 therapeutic products.The aim is to identify a biomarker signature that correlates with clinical response; to measure the predictive power of each signature, a T-test is used to evaluate the difference between measured phenotypes’ cell frequencies (the number of cells in that phenotype divided by the total number of cells in the parent population) among Complete Responders (CR) and Non-Responders (NR). The most statistically significant phenotypes are then selected for manual confirmation using FlowJo. 

4:45 Biomarkers for CAR T Cell Therapy and Combinations

Joseph A. Fraietta, Ph.D., Associate Director, Product Development, Center for Advanced Cellular Therapeutics, University of Pennsylvania

Chimeric antigen receptor (CAR) T cells that target tumor antigens can induce remissions in patients with hematologic malignancies, but only in a subset of subjects with CLL. The mechanisms that potentiate CAR T cell potency are largely unknown. Here we describe a remarkable case that helps clarify determinants of persistence and points to a modifiable epigenetic pathway which may increase anti-tumor activity and therapeutic efficacy of gene-modified T cells.

5:15 Close of Conference Program

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