Scientist / Senior Scientist, Analytical Validation – cfDNA-Based Cancer Screening

Job Description: Scientist / Senior Scientist, Analytical Validation – cfDNA-Based Cancer Screening

Department: Assay Development / Research & Development

Location: [Sunnyvale]

Employment Type: Full-time

Reports To: Director of Assay Development or Head of R&D

Position Summary

We are seeking a highly motivated and technically proficient Scientist or Senior Scientist to lead and execute analytical validation studies for a next-generation sequencing (NGS)-based, cell-free DNA (cfDNA) cancer screening assay, with an initial focus on colorectal cancer (CRC).

The successful candidate will be responsible for designing, executing, analyzing, and documenting analytical performance studies to establish assay accuracy, sensitivity, specificity, precision, reproducibility, robustness, and operational reliability. The role will span the complete analytical workflow, including plasma processing, cfDNA extraction, library preparation, targeted sequencing, bioinformatics data review, and final assay result interpretation.

The candidate will work cross-functionally with assay development, bioinformatics, automation engineering, quality assurance, clinical development, and regulatory affairs teams to establish a robust, scalable, and reproducible assay suitable for clinical validation and future regulatory submission.

Key Responsibilities

1. Analytical Validation Study Design and Execution

• Develop and execute comprehensive analytical validation plans for cfDNA-based cancer screening assays.
• Establish scientifically justified acceptance criteria, sample sizes, experimental designs, and statistical analysis plans.
• Perform analytical studies covering:
• Limit of blank (LoB), limit of detection (LoD), and, where appropriate, limit of quantitation (LoQ).
• Analytical sensitivity and specificity for relevant molecular targets and assay outputs.
• Within-run repeatability and between-run reproducibility.
• Operator-, instrument-, reagent lot-, day-, and site-to-site variability, as applicable.
• Method comparison and analytical agreement against appropriate reference methods.
• Interference, cross-contamination, carryover, and potential sources of false-positive or false-negative results.
• Specimen stability, reagent stability, and critical workflow parameter tolerances.
• Assay robustness and guardband studies for cfDNA input quantity, DNA quality, and other critical process variables.
• Identify assay failure modes, investigate root causes, and implement corrective actions to improve analytical performance.

2. cfDNA and Molecular Assay Development

• Perform and optimize plasma processing, cfDNA extraction, quantification, quality assessment, and sample handling.
• Execute targeted NGS library preparation, including end repair, adapter ligation, indexing, amplification, target enrichment, and library QC, as applicable to the assay chemistry.
• Evaluate the impact of cfDNA input quantity, fragment-size distribution, library conversion efficiency, sequencing depth, and molecular background noise on assay performance.
• Work with mutation detection, DNA methylation, fragmentomic, and other relevant molecular signal types, depending on the assay design.
• Characterize low-abundance molecular signals and assess background error, contamination, and sources of technical variability.
• Establish appropriate controls, reference materials, negative controls, positive controls, and contrived or reference specimens for analytical studies.

3. NGS Workflow and Data Analysis

• Operate and troubleshoot NGS platforms, preferably Illumina, and associated library preparation workflows.
• Analyze sequencing quality metrics, including read depth, coverage uniformity, mapping rate, library complexity, duplication rate, on-target rate, and relevant molecular quality metrics.
• Collaborate with bioinformatics scientists to evaluate analytical pipeline performance, variant or signal detection thresholds, quality-control rules, and reportable-result criteria.
• Perform statistical analyses using R, Python, JMP, SAS, or equivalent tools.
• Generate performance summaries, evaluate confidence intervals and variability components, and assess the statistical significance and practical relevance of observed differences.
• Develop automated data-processing and reporting tools where appropriate.

4. Laboratory Automation and Workflow Optimization

• Collaborate with automation engineers to transfer and optimize cfDNA extraction, NGS library preparation, cleanup, normalization, and pooling workflows onto liquid-handling platforms.
• Evaluate automation-related variability, reproducibility, contamination risk, sample tracking, and failure recovery.
• Support qualification and performance verification of automated liquid handlers and associated laboratory instruments.
• Optimize workflows for medium- to high-throughput processing, including approximately 48–96 samples per batch.
• Develop or review standard operating procedures, instrument methods, liquid-handling scripts, and laboratory troubleshooting guides.

5. Quality Systems and Regulatory Documentation

• Prepare analytical validation protocols, reports, raw-data summaries, deviation investigations, and change-control documentation.
• Maintain traceable records of samples, reagents, instruments, software versions, experimental conditions, and data-analysis methods.
• Support implementation of laboratory procedures and documentation practices consistent with applicable quality-system requirements.
• Collaborate with quality and regulatory teams to align validation plans with applicable FDA requirements, CLSI guidance, and relevant standards for clinical laboratory testing and molecular diagnostics.
• Support design-control activities, risk assessments, verification and validation documentation, and regulatory submission preparation, as applicable to the product's intended use and regulatory pathway.

6. Cross-Functional Collaboration

• Work closely with assay development, bioinformatics, automation, clinical, quality, and regulatory teams.
• Present analytical performance data, study conclusions, and recommendations to project stakeholders.
• Lead technical investigations and communicate complex experimental findings clearly.
• Contribute to assay design decisions, validation strategy, project timelines, and technical risk mitigation.

Required Qualifications

• Ph.D. in Molecular Biology, Genetics, Biochemistry, Bioengineering, Genomics, or a related discipline with relevant hands-on laboratory experience;
• Demonstrated hands-on experience with cfDNA, cell-free nucleic acids, liquid biopsy, or low-input molecular assays.
• Strong practical experience in NGS library preparation and sequencing workflows; Illumina experience is highly desirable.
• Experience designing and executing analytical performance studies for molecular assays or NGS-based diagnostic tests.
• Working knowledge of analytical sensitivity, specificity, LoB, LoD, precision, reproducibility, interference, carryover, and robustness study design.
• Experience analyzing experimental data and applying appropriate statistical methods.
• Strong troubleshooting, experimental design, documentation, and scientific communication skills.
• Ability to work independently while coordinating effectively with multidisciplinary teams.

Preferred Qualifications

• Experience developing or validating cfDNA-based cancer detection or early cancer screening assays.
• Experience with targeted sequencing, low-frequency variant detection, DNA methylation analysis.
• Familiarity with analytical validation programs supporting FDA-regulated molecular diagnostic products.
• Knowledge of CLSI EP-series guidance, relevant molecular diagnostic standards, and FDA quality-system requirements.
• Experience with laboratory automation, including liquid-handling robots and automated NGS library preparation.
• Proficiency in R or Python for statistical analysis, visualization, and automated reporting.
• Experience with design controls, risk management, CAPA, method transfer, and assay lifecycle management.
• Experience supporting high-throughput workflows and clinical laboratory operations.