Seth Stern Email & Phone Number

Menlo Park, Ca, Us

Nexgen Biotools is solving the library prep bottleneck in nextgen sequencing workflows with novel microfluidics solutions.

Fremont, California, Us

Responsible for developing the next iteration of Ultima's clonal amplification technology.

San Diego, Ca, Us

Worked mainly on adapting Roswell's single-molecule detection technology for DNA sequencing applications.

Since successful completion of proof-of-concept for the microfluidic library preparation project, I have been conducting R&D projects aimed at improving GenapSys core DNA sequencing technology. This work has involved development of improved sequencing methods and chemistry that are compatible with GenapSys CMOS chips.

I have been responsible for the development of innovative microfluidic chips and supporting instrumentation to implement NGS library preparation. This has involved creation of a novel digital pneumatic architecture and low cost manufacturing methods to produce devices and systems that are a suitable match for GenapSys’ compact, low-cost DNA sequencing instrument. The digital pneumatic architecture is a programmable engine compatible with multi-step processing, multiple component mixing, magnetic bead-based purification, high-temperature incubation, and PCR.

Athena is exploiting the latest developments in robotics to produce a new liquid-handling laboratory robot that provides radically increased flexibility and programming ease at an affordable price. Athena's technology provides access to virtually the full range of standard molecular biology tools and methods including: microliter-level liquid-handling, evaporation control, PCR, magnetic bead processing, centrifugation, vortex mixing, and a facile interface to microfluidic chips. Unlike competing systems, Athena's robot will be the first compact, low-cost liquid-handling robot to completely automate NGS library preparation protocols.

I worked on their novel and innovative DNA sequencing technology based on electronic detection of polymerase activity. I was mainly occupied with characterization and debugging of the sensor chip using a microfluidic breadboard system and electronic instruments for measuring small currents.

IntegenX has been developing microfluidic chip technology based on pneumatically actuated on-chip pumps and valves constructed with PDMS membranes. I worked on a number of successful and interesting projects there that involved both my molecular biology and engineering skills, beginning with development of a microfluidic chip for mRNA amplification in collaboration with Samsung. More recently, I designed microfluidic chips for parallelized (24X) Illumina NGS library preparation (gDNA and mRNA), PCR, and single cell capture. These efforts included development of a novel parallelized, digital pneumatic microfluidic architecture and improved chip fabrication materials and methods that eliminated problems associated with the permeability of PDMS. In addition, I was technical lead for a DITRA-funded novel pathogen detection project based on DNA amplification (MDA with phi29 polymerase) and Illumina NGS, as well as for the research phase of a project to develop an NGS library preparation liquid-handling robot, which is now an IntegenX product.

Us

I was mainly involved in two activities: first, invention of methods and devices for automated, miniaturized mRNA amplification, which involved successful application of for a Phase I SBIR grant to the National Institute of General Medical Sciences (NIGMS), and second, development of methods and chemistries for automated and miniaturized total RNA, polyA+ RNA, and genomic DNA sample preparation. These methods produced nucleic acids with yields and purities equaling or exceeding those of market leading kits. mRNA generated with polyA+ mRNA purification chemistry was successfully amplified and analyzed on Affymetrix microarrays.

Waltham, Ma, Us

I was involved with invention and development of miniaturized, sample-to-answer nucleic acid processing systems comprising polymeric, laminated microfluidic chips for nucleic acid purification with nanoporous aluminum oxide membranes, and thermocycling for RT-PCR. These chips interfaced with LabVIEW-driven valves, syringe pumps, and epi-fluorescence optics. In addition I was involved in the development of an automated silica-based pathogen DNA and RNA purification system using a polymeric, laminated microfluidic chip carrying a silica membrane, and LabVIEW-driven valves and syringe pumps.

ChemAutomaton proposed development of technologies for automated, massively parallel, target-directed small molecule (ligand) discovery and optimization, based on iterated DNA-programmed organic synthesis, target-specific selection, and PCR amplification. Such methods represent an alternative to traditional medicinal chemistry and high-throughput screening drug discovery technologies. They are essentially elaborations on SELEX (or in-vitro genetic selection) methodology developed for aptamer discovery, in which highly diverse synthetic DNA libraries are used not only to encode but also program synthesis of small molecules, which remain associated with their encoding DNA oligomer (thereby linking genotype and phenotype). Specifically, ChemAutomaton proposed to miniaturize and automate a procedure developed at Stanford University, using microfluidic technology to produce a bench-top small molecule (ligand) discovery/optimization instrument. Business plans and SBIR grant applications were prepared, and the technology was presented to potential investors.

Glendale, California, Us

Caliper was developing a microfluidic chip for real-time PCR based on a novel thermocycling strategy that involved joule heating of PCR buffer in microfluidic channels. I was first able to successfully conduct proof-of-concept experiments, and I then designed a microfluidic "sipper chip" that could detect SNPs in gDNA. I subsequently developed methods for conducting alternating electric current directly into microfluidic channels based on exploitation of the electrical double layer present at metal-electrolyte interfaces.

For IBIS Therapeutics: Identification of potential antimicrobial drug targets in ribosomal RNA and design of “RNA analogs" useful in high-throughput screening. I identified sub-domains in bacterial 16S and 23S ribosomal RNA with potential utility as targets for small molecule protein synthesis inhibitors and designed small RNA analogs for use in in-vitro screens.For Molecular Machines: Invention of methods for in-vitro evolution of nucleic acids and small molecules. I generated IP for these systems.For Allelix (Toronto, Canada): Invention of array-based, high-throughput RNA structure probing for discovery of small molecule RNA-binders. I adapted methods developed at UC Santa Cruz for RNA structure probing (during my PhD research) for drug discovery applications.

My postdoctoral research at Cold Spring Harbor Laboratory was concerned with the human homeodomain- (actually POU domain-) containing transcription factor Oct-1. As an assistant professor, I successfully competed for and competed a NIH R01 research grant for research on Oct-1—VP16 interactions. These studies involved the development of a yeast two-hybrid method to screen for human analogs of viral transcriptional activator proteins. In addition, I successfully competed for and competed a second NIH R01 research grant for research on RNA structure and function, and my group published original research in the leading scientific journals Nature and Cell on this subject. We identified small molecule binders of the decoding region of 16S rRNA and the HIV Rev-Response Element (RRE) using chemical structure probing methods.

Cold Spring Harbor, New York, Us

Successfully competed for and competed an NIH postdoctoral training grant. I was able to show that the viral transcription factor VP16 recognizes amino acids in the homeodomain (DNA-binding domain) of the human homeodomain protein Oct-1, an unexpected and significant observation at the time that resulted in several publications including the leading scientific journal Nature.

Santa Cruz, Ca, Us

My PhD research in Professor Harry Noller's lab at UCSC concerned protein--RNA interactions in the 30S subunit of the E. coli ribosome. I participated in the development of new chemical/enzymatic structure probing and footprinting methods that relied on reverse transcription of modified RNA. Using these methods we were able to localize binding sites for numerous 30S subunit proteins, as well as protein-induced conformational changes, in 16S rRNA. We then used the known three-dimensional coordinates for the centers of mass of the proteins to speculatively fold 16S rRNA in three-dimensions, based on these binding sites.

Santa Clara, California, Us

I was very fortunate to assist in the development of Intel's CMOS process technology (P444). I was involved with: validation of design rules for new device fabrication technology, characterization of the performance of CMOS static RAM test vehicle, full-die simulation (using Intel’s proprietary SPICE derivative) of a 64K CMOS dynamic RAM, characterization of 64K CMOS dynamic RAM performance, and circuit and layout modifications for revisions of 64K CMOS dynamic RAM.

Phd, Molecular Biology Of Rna

Bsee, Electrical Engineering