My dream in Berkeley 2

Here are the updated and additional essays for applying the job positions in Berkeley Lab or UC Berkeley. Hopefully I will be lucky!

 

 

 

Diversity, equity, and inclusion

 

I want to work at Berkeley Lab / UC Berkeley because advancing diversity, equity, and inclusion is exact the goal of my life! When my parents came to the U.S. in the early 1970s, they were inspired so much by the student-led movements such as the protest at People’s Park at UC Berkeley! After they finished their graduate studies, they decided to go back to Taiwan and also become social activists, organizing demonstrations and civil disobedience to protest against the authoritarian regime at that time. After Taiwan transited into a democratic country, my parents have continued to push for more social welfare programs to help the and under-served populations, because they firmly believe that all people should be treated equally regardless of their looks, beliefs, or socioeconomic statuses. (More of my family's story at here: The Origin of My Life (2020 update))

 

Inspired by my parents’ great work, I decided to join Lin-Sen Community Development Association in Taipei City when I was a college student. I worked with the other students to conduct surveys to seek the residents' opinions on the local facilities and organize events for the community development plans. We were so passionate about getting everyone in the community to participate in the decision-making process for the community planning, because we believed the bottom-up approach is the only way to empower the minority or under-served groups.

 

After I finished my graduate studies, I have also kept pursuing for working in the public sectors, and luckily, I have finally been able to work in a public institution since 2019! I feel so enthusiastic about my current work by knowing that my work can benefit all the newborns in my state! By automating the tedious DNA extraction procedures and multiplex qPCR runs, we have been able to screen 3000 newborns for spinal muscular atrophy (SMA) in just a day! The superb efficiency of our screening assay makes it possible to help all the newborns in my state to detect SMA early enough to avoid the huge amount of burden in their life. By eliminating the disadvantage of the babies born in the poor families who cannot afford the private newborn screening, my colleagues and I have truly advanced diversity, equity, and inclusion in our state! That is also why I want to apply for this position to further contribute my expertise in high throughput robotic system to automate the detection of more genetic diseases!

 

 

 

 

 

 

Method development experiences

 

I am familiar with analytical method development from both my graduate studies in biomedical engineering and my working experience in developing both point-of-care diagnostic products and high throughput genetic diseases screening assays.

 

In my dissertation research in a medicinal chemistry laboratory at UC Davis, I used nuclear magnetic resonance (NMR) (Bruker Avance 600 MHz spectrometer), electron paramagnetic resonance (EPR), and UV-Vis spectroscopy, to study protein structure and functions, in particular protein-lipid interaction and its role in metabolism regulation and bioenergetics. I calibrated the NMR machine for the target samples, set up the probe temperature, pulse sequences, and the other parameters, and created the automated data acquisition schedules with Bruker Topspin software. I have demonstrated that hemoglobin and myoglobin can bind long chain fatty acid at the presence of oxygen and built mathematical models for intracellular fatty acid transport based on the diffusion and binding activities. These findings have been published in 5 academic journal papers.

 

In my previous work as the R&D Scientist at Company O, I was developing multiplex lateral flow immunoassays for urine and saliva testing for the drugs of substance abuse and enzymatic colorimetric assays for detecting alcohol and metabolism diseases. The multiplex immunoassay device can be used to detect six types of the drugs of substance abuse: amphetamine, opiate, cocaine, MDMA, benzodiapenes, and tetrahydrocannabinol (THC). In order to increase the sensitivity of the lateral flow diagnostic assays, I optimized the conjugation process between antibodies and antigens or gold nanoparticles and the formats and materials of the testing devices for sensitivity improvement. I also conducted organic synthesis of the hapten molecule for developing the new THC antibodies that can recognize more types of the THC metabolites in saliva and urine. Working in a small company, I frequently participated in the manufacturing process of the lateral flow devices, such as preparing the reagent solutions, assembling the different components into the final products, labeling, and packaging.

 

In my previous work as a lead scientist in Company D, I have contributed most of my work in the research and development of 1D and 2D lateral flow hybridization assays for detecting trace quantity of oligonucleotides for the application of DNA containing ink in counterfeit prevention. I have successfully created several new device prototypes and methods and synthesized novel protein conjugated nanoparticles with chemical or physical surface modification methods and emulsion polymerization to increase the sensitivity of the assays. My other important task was to create new ink formulations to ensure the DNA could be detected in a variety of environment or ink conditions. In addition, with my knowledge of primer selection from working with oligonucleotides, I was able to mentor the intern there for his bachelor’s thesis project in developing a molecular diagnostic method to identify the source of meat in the sausages.

 

In my current work as a research scientist, I have laid the groundwork for incorporating the high throughput robotic system (Hamilton Microlab StarPlus) into the newborn genetic screening assays for spinal muscular atrophy (SMA) with multiplex qPCR, with the capacity of screening 3000 newborns per day. The DNA from the newborn dried blood spot (DBS) is extracted by the robot, and the DNA extracts are aliquoted with qPCR reagents and ready to be quantified by the qPCR machines (QuantStudio™ 7 Flex Real-Time PCR System) for their SMN1 genes. I am responsible for the development, maintenance, validation, and troubleshooting of the robotic operations according to the Clinical Laboratory Improvement Amendments (CLIA) guideline. I work with both hardware and software of the Hamilton robots to ensure smooth coordination between the different components on the robotic system, such as the centrifuge, incubator, shaker, and plate sealer /peeler. I have also optimized the liquid class, a set of liquid handling parameters, to ensure the correct volumes are aspirated and dispensed by the robot. In addition to my main duties, I also help my coworkers to analyze the qPCR results and perform the finalized data review through our laboratory information management system (Perkin-Elmer Specimen Gate).

 

 

 

 

 

 

Quality control experience

 

In my previous job as an R&D Food Technologist at Company M, I have been familiar with the compliance evaluation from assessing the regulatory documentation (product specification, ingredient and allergen declaration, Kosher certification, current 3rd party audit, lot formation explanation, letter of guarantee, country of origin, and MSDS) for British Retail Consortium (BRC) audit. I checked if all the required documents for the ingredients used in my company were updated. If they were missing or expired, I would collect them from the suppliers. In addition, I also participated in the sensory and shelf life testing of the bakery food products collected at different manufacture dates, and the testing criteria were surface appearance, topping application, bake color, taste, texture, and packaging.

 

While developing point-of-care lateral flow devices at Company O, I have learned to follow the ISO 13485 guideline in laboratory management. Since my company has been a contracted manufacturer for the bigger companies such as Alere, I helped preparing the required documentation for the inspection from the client companies. In my assay development work, I also followed the Substance Abuse and Mental Health Services Administration (SAMHSA) guideline for the cut-off concentration for the drugs of substance abuse. In general, the drugs in the saliva or urine should be detected at 1.5x the cut-off concentration (as the limit of detection) and not be detected at 0.5x the cut-off concentration.

 

In Company D, I also performed stress and shelf-life testing for the manufactured products. In addition, I had been in contact with FDA for the compliance of the application of our DNA ink products on food and skin contact surfaces. I also tested for the effectiveness of substituting the surfactants and biocides in our DNA ink with the FDA approved ones.

 

In my current job, I have been responsible for creating the quality control protocol of the high throughput robotic system (Hamilton Microlab Starplus) used for the newborn genetic screening assay for spinal muscular atrophy (SMA), based on the guideline of Clinical Laboratory Improvement Amendments (CLIA), since we are processing human specimens. The robotic system performs both DNA extraction from the newborn dried blood spots (DBS) and preparation of the DNA samples for the subsequent qPCR reactions. I also participated in the quality program of the reagents and reference materials (the control samples with known DNA concentration) used in the assay.

 

The two most important aspects of the quality program are validation and verification. In the validation process, we want to check if the robots do what we expect them to do. The two important concepts in the validation process are precision and accuracy. For the precision, we want to check if the output values from the robots are consistent. This is indicated by the coefficient of variation (CV), the ratio of the standard deviation to the mean of the measured data. For the accuracy, we want to know if the measured values are close to our expected values. This is indicated by the relative inaccuracy (R), the difference of the mean of the measured values and the expected value divided by the expected value. The volume and temperature values of the robotic system are validated if both the precision and accuracy fall within the ranges of our criteria. For the validation of the reagents, reference materials, and qPCR machines, the threshold cycle (CT) values from the qPCR reactions that represent the quantity of the genes in the samples are measured. Since there are no certain expected CT values for them, only the precision studies are performed. In the verification process, we want to check if the different robots or qPCR machines, or the reagents and reference materials from the different preparation dates, give us the same results. For the temperature and volume of the robotic systems, it will be sufficient if both precision and accuracy data from the different robots fall within the validation criteria. For all of the other verifications, the measured CT values from the old samples, the new samples, and the combination of the two groups should all have their precision measurements fall within the 95% confident interval.

 

My coworkers and I have carefully documented all of our laboratory activities, including our validation and verification work, for the CLIA inspection from Centers for Medicare & Medicaid Services every 2 years. We just passed our latest inspection in May 2021!