Technology Development
Archived Material
In recent years the Technology Development Group at the Stanford Genome Technology Center (the former Stanford DNA Sequencing and Technology Center) was responsible for developing custom instrumentation and novel technology to increase the throughput and lower the cost of DNA sequencing and analysis. The links below give an overview of the projects we have completed and the instrumentation and software we have created.
Instrumentation which is exported or commercialized from our lab carries the SUTECH® logo developed in conjunction with the Office of Technology Licensing.
This work was funded by the National Human Genome Research Institute.
Archived Projects
Linked
Thermocycler
Commonly available thermocyclers implement a 'hot-plate' design. That is a metal plate which is designed to accept a 96-well micro-strip. This plate is actively heated and cooled to cycle through the appropriate temperatures (MJ Research). While such designs have proven reliable, they do suffer from a few fundamental limitations.
Capillary Array Electrophoresis Sequencer
A fast, automated and massively parallel method of DNA sequencing will complete our modular, high-throughput (10000 samples/day) sequencing system. A large reduction in the cost per base is expected due to the very small sample volumes (sub-microliter) needed for Capillary Array Electrophoresis (CAE) sequencing.
Oligonucleotide Synthesizer AMOS 2
A facility has been developed at the Center which is capable of synthesizing oligonucleotides that are vital to the DNA sequencing process. The single strand sections are known as primers and are necessary to locate specific sites and regions on a DNA molecule and allows sequencing of precisely known regions of the molecule to take place.
Arrayer
The micro arrayer is a high-capacity system developed to monitor the expression of many genes in parallel. The instrument is used to hybridize cDNA drops onto coated slides, thus forming cDNA microarrays which are then scanned for fluorescence. By using steel quills, cDNA solution is dipped from 384-well plates and dotted onto up to 48 slides.
Scanner
We have constructed a two-color (green and red) laser-fluorescence-based scanner for scanning a medium-density array of cDNA probes hybridized onto coated glass slides. A typical slide contains upto 10000 probes, arrayed in a 1 sq. inch area. Two-color laser scanning allows quantitative studies of gene-expression in two samples simultaneously.
Automated Sequencing System
The massive amount of DNA sequencing necessary for the completion of the Human Genome Project and for the sequencing of other large genomes will require development of technology to increase sequencing throughput and to lower its cost. Our Technology Development team, in collaboration with U.C. Berkeley and Affymetrix Inc., is developing a modular automated sequencing system with the goal of sequencing 1 Mb/day of assembled sequence at a cost of $0.01 per base.
Point-sink Shearer: a Hydrodynamic DNA Shearing Device
Random DNA fragments are required to construct efficient libraries for genomic sequencing & gene cloning strategies. We have built and tested an automated device that generates random DNA fragments by hydrodynamic shearing. The method improves on other fragmentation techniques currently being used. It is inexpensive, easy to use, reproducible, and versatile.
Plaque Picker
The picking of isolated viral plaques or bacterial colonies has traditionally been one of the most tedious and time consuming tasks associated with shotgun sequencing. We have developed a picker capable of processing 1 input dish in ~3 minutes. Furthermore the picker is equipped with plate handling servers which allow the instrument to process up to 80 input dishes without any human intervention.
High Capacity Shaker
We have developed a high capacity, atmosphere controlled shaker for growth of e-coli and phage in 96-well microtiter plates. The shaker holds four 14-plate cassettes (56 microtiter plates max. capacity) and shakes (movie) them in a synchronized manner to eliminate all vibrational forces and moments, which normally would be transferred to the base by the large rotating masses.
Template Preparation Machine
We have developed an instrument for automated purification of ssDNA from phage supernatant based on a glass fiber purification protocol. The instrument is served by two server arms. The input arm serves microtiter plates containing M13 and e-coli pellets to the instrument by retrieving them from our standard 14-plate cassettes.
Flow Through Micro-Centrifuge
We have recently developed a novel technology to increase throughput and flexibility of protocols that require centrifugation. Regular centrifugation, though potentially automatable, remains too unwieldy and slow a process for high throughput instrumentation. Filter based protocols can replace most but not all centrifugation steps and can be expensive due to the cost of the disposables involved.
Plasmid Preparation Machine
The robot utilizes a patented 96-well flow-through microcentrifuge developed in our group. Cell pelleting and resuspension have traditionally been performed manually in a 96 well plate centrifuge and vortexer. The automation of these steps allows plates of bacterial cultures to be processed directly without technician intervention.
ACCESS, an Automated Cell, Compound, and Environment Screening System
The Automated Cell, Compound and Environment Screening System (ACCESS) is used for pre-screening and screening compounds against the yeast knockout library for Haplo-Insufficiency Profiling, Over-Expression in Yeast and for high-resolution phenotypic analysis of other single cell organisms.
Development on High-throughput Sequencing Technology: emPCR Titration and Barcode Design
454 sequencing technology is a high throughput DNA sequencing platform based on Pyrosequencing technology. The current platform has an average read-length of 250 bases and it generates over 100 million bases in one single run. At Stanford Genome Technology Center, we use this platform from whole genome sequencing to amplicon sequencing for a wide range of applications.
Magnetic Resonance Imaging and Spectroscopy for the Discovery of New Human Disease Models
Magnetic resonance imaging (MRI) and spectroscopy (MRS) is increasingly proven as a useful tool for the study of development in living organisms and thick or opaque tissues. The advent of MRI contrast agents which can act as reporters by responding to chemical concentration and gene expression, coupled with the robustness of Drosophila as a model organism, equipped with a diverse array of powerful genetic tools, now makes real time in-vivo imaging of complex processes a potential approach for the elucidation and study of human disease models.
Yeast screen robot for Haplo Insufficiency Profiling (HIP)
The objective of this project is to provide an automated system for haploinsufficiency profiling (HIP) screens. The screen system is a pool of gene deleted yeast grown against a drug at a concentration that inhibits the yeast pool growth rate to 80% of wild type (wt). For high throughput and automation the screens are grown in 48 or 96 well plates.
High-throughput Pyrosequencing for large-scale genetic analysis
Pyrosequencing, a non-electrophoretic method for DNA sequencing is emerging as a popular platform for DNA analysis (Ronaghi et al. 1996, 1998, 2001). This technology has the potential advantage of accuracy, ease-of-use, and high flexibility for different applications. The technique dispenses with the need for labeled primers, labeled nucleotides and gel-electrophoresis, and it supports high levels of automation.
Nanobiotechnology Projects
Our Thermosequencing is a novel sequencing technique with the potential to yield significant improvements in cost and read length; thermosequencing also has several distinct advantages over existing synthesis techniques: neither expensive fluorescent labels, reporting enzymes, nor optical detectors are required and native DNA polymerase may be used.
Archived Projects
Unlinked
- Biosensers Technology Group
- Nanoneedle
- GCMB Microfluidic Biosensor Platform
Last updated May 2025