MY CAREER

I have spent a 20-plus year career studying, developing, and producing analytical systems. To augment my resume, what is offered here is a brief description of some of my accomplishments at my last three companies. For a more complete description of my career, please see the Full Bio link above.

STAFF SCIENTIST FOR BECKMAN COULTER

The skills I acquired while working for Beckman Coulter include system integration, system optimization, system verification/validation, production line support, calibrator and control value assignment (VA), assay standardization, data analysis, communication, and leadership.

Over the course of my career I was involved with system integration, verification and validation activities for the Astra, Lablyte, CX3, CX5, CX7, Immage, LX20 and DXC platforms. Here performance was reconciled with design requirements. Experimental data was also used for regulatory submissions.

As a member of material review boards, I participated in problem solving for reagent and instrument production lines. Here we designed and performed experiments to justify deviations and support production process changes. Changes included specification and testing refinements as well as hardware and materials updates.

To the greatest extent ranges published in control inserts reflect the total variation of assay systems and the errors in the estimates of target values. I used this construct for many control VA projects. In addition, I developed a computationally simple method to assign control target values by considering the values from other methods (U.S. Patent 7312083). For an assay to produce accurate results, calibrator VA must properly integrate with many aspects of system design. Assay signal processing, calibration, process replication, and links to external accuracy bases are some of the important considerations. Dr. Jeff Vaks and I wrote a Clinical Chemistry article describing one particular VA project, Evaluation of assigned-value uncertainty for complex calibrator value assignment processes: a prealbumin example. As part of the larger IVDD compliance project, I characterized the calibrator uncertainty for all Beckman Coulter products.

I completed some specialized data analysis projects. One, described in U.S. Patent Application 20060241904, offered a method for robust variation estimation. For another, highlighted in the Clinical Chemistry paper Effect of analytical error on the assessment of cardiac risk by the high-sensitivity C-reactive protein and lipid screening model, I used Monte Carlo simulations to evaluate a clinical model.

In the area of assay signal processing, one of my notable achievements was optimizing the spectroscopic parameters for the Valproic Acid assay. This led to significant improvements in assay performance.

Later during my tenure at Beckman Coulter I was the Project Manager (relatively small project) for the team that first applied a Cystatin C assay (Dako reagent) to the Immage system. Also, I was the development team leader for the business critical high sensitivity CRP re-standardization project.

LEADER AND TECHNICAL CONTRIBUTOR FOR QUALIGEN

For Qualigen, I led and technically contributed to current business and next generation development.

I led the standardization and re-standardization efforts for most of the Qualigen assays. As part of this effort, I discovered formulating FT4 solutions is difficult. To solve this problem, I developed a tool for spiking solution characterization using non-linear dilution vs. concentration profiles. Because of its efficacy, this approach was generally adopted for formulation of all calibrators, controls, and standards produced at Qualigen.

Instrument production stopped when the process for determining critical magnet face dimensions did not function. Because I solved this problem, I was offered an unscheduled 10% pay raise.

To replace manual data entry, I developed and implemented a Fastpack instrument data collection system. The work hours saved as a result of this implementation certainly range in the thousands. I then developed and implemented results trending (Xbar and R charts) in product final test. For many quality assessments, looking at trends across reagent lots and instruments, rather than individual assessments, has advantages.

For the best-selling PSA assay, I developed an alternative method, using optimization techniques, for handling the assay signal versus time data. This led to approximately a 25% reduction in total imprecision.

To improve instrument reliability, we designed an instrument burn-in process to exercise pneumatics, the motor transmission assembly, and photomultiplier tube (PMT). I automated the analysis of the resultant process data.

To improve the robustness of reagent pouch filling, I removed an unnecessary fill check and introduced the use of in-line debubblers (common in HPLC).

Due to obsolescence, I identified a replacement PMT. To integrate and implement, I developed a signal transformation model to functionally equate old and new PMTs.

When the stability of FT4 reagent became an issue, I developed and led implementation for a signal decay correction model that led to an increase in shelf life from 4 months to 8 months.

During reprieves in current business activity, and because the use of whole blood is critical for a CLIA waived device , I led the development of a plasma from whole blood separation device. The resultant module could deliver a quantitative volume of plasma (U.S. Patents 9664668, 9903799).

In order to fulfill another CLIA waiver requirement, I led the development of a machine vision based method to verify proper sample introduction The process proved to be a sensitive method for sample metering (U.S. Patent 20180342062).

I wrote requirements documents for the instrument and the consumable. The high-level documentation described the hardware and software user interfaces, engineering controls required for CLIA waiver, and key subsystem interactions. The detailed hardware portion included many considerations taken from the first-generation product along with the new plasma separation device and sample metering vision system aspects. The software specifications included detailed descriptions of all analytical processes.

To prepare the instrument for formal verification and validation, a great deal of system optimization was required. Numerous subtle and game ending problems involving the mechanics, electronics, software, and human factors considerations were solved. We also solved a number of problems involving integration of the plasma separation device with the reagent pouch.

To automate generation of reagent lot specific signal versus concentration curve parameters, I wrote a VBA software application. The tool was based on my detailed software requirements for results calculations.

Some poor cell phone pictures of the instrument in action can be viewed here. Shown are the main screen, a test in process screen, patient result screen, calibration/QC result screen, and instrument self-test screen.

When I left Qualigen the instrument was in the process of Clinical Validations. We designed and developed a GREAT CLIA waivable instrument. This analytically sound system is easy to use and has a flexible assay application architecture.

DIRECTOR, DESIGN CONTROLS and DATA ANALYTICS

Amprion is a cutting-edge biotechnology company with a CLIA certified and CAP accredited high complexity laboratory that focuses on neurodegenerative disease diagnosis and I am proud to have served on this team. This is a great company filled with talented people on a noble mission. Although I cannot mention many of my accomplishments at Amprion as most are part of active projects, I can say I had a tremendous experience. While at Amprion, the areas of my professional presence that expanded the most include:

• Experimental design and analysis in qualitative space. Up until this point my experience primarily involved quantitative measurement systems.
• Seed amplification assay technology
• Understanding of operations in a clinical laboratory. Up until this point (with Beckman Coulter and later Qualigen) I had been involved in the development and support of systems to be sold into laboratory operations space.
• I’ve gained some understanding of the clinical and pathological aspects of neurodegenerative disease.
• Application of FDA Design Controls to Lab Developed Test (LDT) development/implementation.
• As the lab's cybersecurity representative, I learned about quality management system relationships to HIPAA and GDPR compliance.

As part of our efforts, we have developed and implemented a clinical laboratory test (SYNTap®) that measures the presence of misfolded alpha-synuclein which is the definitive biomarker for diagnosing synucleinopathies (Parkinson’s Disease, Dementia with Lewy Bodies (DLB), Multiple System Atrophy, and mixed pathology Alzheimer’s). This most certainly has moved the state of the art forward.

As evidence, scientific reporting in this area has grown significantly in recent years. For example, one paper from the Amprion clinical laboratory (Dr. Kendal Jensen and I are the primary contributors) highlights some assay features. Here, through the analysis diagnostic error rates as a function of cohort, accuracy of this assay is suggested. It was published in the Journal of Neurology and is titled “Seed Amplification Assay Results Illustrate Discrepancy in Parkinson’s Disease Clinical Diagnostic Accuracy and Error Rates”. Also, I contributed to another paper from our laboratory (Neurology) titled, “Association of CSF alpha-synuclein-SAA seed amplification results with clinical features of possible and probable dementia with Lewy bodies”. This paper, which involved the study of a DLB cohort, suggests the clinical diagnostic process would be improved through the use of the Amprion assay.

Lastly, I played a minor role (data collation and transfer) in developing this Alzheimer's & Dementia manuscript, Misfolded α-synuclein co-occurrence with Alzheimer’s disease proteinopathy.