Biomedical - Biotech

Mass-Producing Inexpensive Flow Cells For DNA Sequencing

Issue:

Glass is an ideal structural and chemical material for DNA sequencing because it is optically transparent, thermally stable, chemically inert, and friendly to biological samples. However, it has not been possible to mass produce glass slides with the tiny channels needed for analyzing DNA samples efficiently and inexpensively.

Conditions have to be just right for DNA analysis. The flow cell is the critical interface between the optical readout instrument, the sample, and the complex chemistry used to read the genetic information in the sample.

Flow cells have tiny lanes etched into their surface that contain the patient’s DNA and all the chemistry that is required for the sequencing process to occur. Inside the DNA sequencer, the lanes are precisely aligned under a moving laser beam that reads the optical signal of each particular nucleotide base. This design is a critical component of DNA sequencing.

Previously, it was common to create patterns in the glass by covering it with a mask and then exposing the glass to light. The exposed sections would etch when placed in a chemical bath, leaving only the sections that had been covered. This produces an open trench that is then covered with glass and bonded to create an embedded channel. The disadvantages of this technique were that it required too many costly steps and did not allow for any nuance–either the glass was exposed through the mask and etched away or it wasn’t.

Aerospace Solution:

Developed in the mid-1990s, Aerospace’s patented technique for manipulating a special photosensitive ceramic-glass compound, which involves a process for micro-machining glass for space applications, has been licensed Illumina, a company that makes DNA sequencers. Illumina uses Aerospace technology to produce the glass slides, called flow cells, which hold DNA samples for DNA sequencing. These glass slides are an important part of a new DNA sequencing process that is made possible by a new DNA sequencer that employs recent advances in chemistry.

The Aerospace method for micro-machining glass works by using a laser that is focused at the precise area in the glass where the miniaturized structures are to be placed. The goal is to expose the material without physically damaging it so that the exposed areas will dissolve away when the glass is placed in a chemical bath.

The process invented at Aerospace by Dr. Henry Helvajian, Bill Hansen, Lee Steffeney, Dr. Peter Fuqua, and Dr. Frank Livingston allows for the creation of much more sophisticated shapes within the glass because, by using a directed laser beam, one can control the depth of etching on the surface or even embed structures within the glass.

The team originally developed the process for micro-machining glass in order to make miniature propulsion systems for small satellites. Since then, the technique has been adapted to create tiny antennae for broadband wireless systems.

Finding a licensee for technology developed at Aerospace is a process that Quintero and others involved approach with great consideration. Their goal is to ensure that the investor is the correct fit for the technology and that the greatest benefit will be derived from issuing the license.

Mass producing glass flow cells is just one application for the technology that Helvajian helped to invent. It has been used to create ink jet printer heads and diode spacers and is currently being tested for use in creating gas and chemical sensors and semiconductor components. These are just a few of the places that Aerospace technology might find its way into daily life in the future.

Results:

This process has enabled the cost of DNA sequencing to be greatly reduced–from millions of dollars to around $4,000–making sequencing an individual patient’s DNA affordable.

The ability to sequence an individual’s DNA opens up a whole new realm of potential treatments for patients with terminal diseases, such as cancer, and for patients with diseases that doctors are unable to diagnose. By sequencing a patient’s DNA, doctors can identify precisely what is going on in the person’s body. In the case of patients with cancer, this allows doctors to more accurately determine which drugs and treatments will be the most effective in fighting the disease. For people with cases that are difficult to diagnose, DNA sequencing can reveal mutations in the body that are causing diseases.

“What we have had is about 15 cases where people have had their whole human genome sequenced,” explains Steve Barnard, vice president at Illumina, the company that makes the new DNA sequencers. “From that information they’ve been able to understand the disease better and therefore go back to the experimental drugs or select the right drugs for those diseases. The people that have done this, most of them have had radical improvements in their disease based on getting the correct drug for their disease. Now, the only way you get the correct drug is to really understand your particular disease state.”