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November 15, 2003

CEPHEID
Sunnyvale, Calif.
 
Pedigree: Based on research from Lawrence Livermore National Laboratory that led to development of a miniaturized PCR thermal cycler.

Status: Has hundreds of customers for Smart Cycler, its rapid DNA amplification product; working toward the release of GeneXpert, a tabletop analyzer that works with sample-prep cartridges and performs tests in 30 minutes. Created portable test kits for the DoD for anthrax, plague, botulism, and tularemia. Has a test for Group B strep through a joint venture with Infectio Diagnostic. Also developing tests for tuberculosis, cancer, and various childhood infectious diseases.

Grants and contracts: $175 million from the U.S. Postal Service (indirectly, through a partnership with prime contractor Northrop Grumman) to develop a biohazard detection system, now being tested. Also holds grants from NIH.

"Our system is very small and close to solid state with a minimum of moving parts. It can fit ultimately anywhere — into a doctor's office, the operating room, labor and delivery." John Bishop, CEO 
Other support: Raised more than $30 million in venture capital from 1997 to 2000; IPO in June 2000 raised $30 million. Key investors include Advanced Technology Ventures and Medtronic.

Technology: Disposable cartridges designed to extract DNA from a variety of sample types. Cartridges work with a module that can amplify the DNA automatically, and detect and quantify up to four targets simultaneously.




HANDYLAB Ann Arbor, Mich.

 Detail of the fully processed silicon wafer used in HandyLab's integrated device. Each "square" corresponds to one device. 

Pedigree: Founded by two University of Michigan Ph.D.s from David Burke's molecular genetics lab, based on microfluidics research.

Status: Hope to have prototype handheld device in clinical testing by late 2004.

Grants: $2 million from NIST Advanced Technology Program to develop portable DNA analysis device using electrochemical detection.

Other support: Raised $8 million from two rounds of venture capital funding, from the University of Michigan's Wolverine Venture Fund, Hewlett-Packard, EDF Ventures, Ardesta, XR Ventures, and SBV Venture Partners. Looking for a third round of $5 million.

Technology: HandyLab seeks to scale down all procedures of a standard genetic testing lab to the size of a small, disposable cartridge. The microfluidic system relies on internally generated pressure to propel nanoliter liquid plugs through a microchannel network. Initial areas of emphasis include Group B strep detection in pregnant women during labor and infectious diseases. Also developing a prototype for SNP detection. Hewlett-Packard plans to develop a PDA-size device to drive and control HandyLab's cartridges.




NANOGEN San Diego

 The laptop-size DUST ONE semiconductor-based microarray platform can identify bioterror agents such as anthrax within minutes. 

Pedigree: Based on research of company founder Michael Heller, now a professor of bioengineering at University of California at San Diego.

Status: Markets NanoChip microarray and workstation to labs for detecting SNPs and short tandem repeats (STRs). Has tests for factors associated with cardiovascular disease, cystic fibrosis, Alzheimer's disease, and beta thalassemia, among others. Working on portable device funded by government agencies for biowarfare detection of such agents as anthrax, plague, and smallpox. Recently signed an agreement with Prodesse to develop microarray-based products to detect influenza, pneumonia, adenovirus, herpes, West Nile Virus, and SARS.

Grants: More than $11 million from DoD's DARPA and Dual Use Science and Technology programs.

Other support: Raised $64 million in 1998 in an IPO and a private placement with investors Becton, Dickinson & Co., Hoechst AG, and others. Recently did a private placement to raise $16 million.

Technology: NanoChip uses the natural positive or negative charge of biological molecules to concentrate them at given sites through applying a current. Nanogen's technology involves electronically addressing biotinylated DNA samples, hybridizing complementary DNA probes and removing all but the targeted DNA. On-chip amplification is under development, using a non-PCR technique licensed from partner and investor Becton, Dickinson & Co.




NANOSPHERE Northbrook, Ill.


Pedigree: Northwestern University's Institute for Nanotechnology; original research by Chad Mirkin and Robert Letsinger.

Status: Company launched in 2000. No products on market as yet; two benchtop devices are in testing. Aiming for handheld prototype by year-end.

Grants: $1.5 million from NIH to develop detectors for SNPs associated with hypercoagulation disorders and colorectal cancer; a multimillion-dollar sum from the Technical Support Working Group, a government anti-terrorism agency, to develop portable detection systems for bioterror agents in water samples.

Other support: A third round of $15 million in venture funding closed earlier this year, making the grand total $23.5 million, from Takara Bio of Japan, Lurie Investments, NextGen Partners, and individual investors.

Technology: DNA sequences are attached to gold nanoparticle probes. The probes are used to bind and signal the presence of a specific DNA sequence, and they change color if the target is present. For the handheld device, Nanosphere is binding the probes to micro-arrays of electrodes, so they produce a current when the target is detected. Initial research shows accurate results can come from extremely small samples, which the company says eliminates the need for PCR or other amplification techniques.

 Nanosphere's DNA probe is constructed so that its nucleotide sequence is complementary to a specific region of the DNA target. If the target sequence is present in the test sample, the DNA probe will bind to the target, causing the particles to change from red to blue. 




QUANTUM DOT Hayward, Calif.


Pedigree: Based on research on semiconductor materials at Bell Laboratories in the 1970s, and later by two of its former scientists, Paul Alivisatos (UC-Berkeley) and Moungi Bawendi (MIT).

 Qbead microspheres encoded with different colors of Qdot nanocrystals impart identifying 'codes,' allowing highly multiplexed, parallel assays to be performed. 
Status: Sells quantum dots directly and through resellers. Recently entered into a co-development agreement with Matsushita/Panasonic to develop DNA analysis devices, including, eventually, a portable device. First product of collaboration — a tabletop analyzer said to be 200 times faster than existing instruments — announced in September. Main focus is cancer tumor staging.

Grants: $5.6 million from NIST Advanced Technology Program to develop blood fingerprinting technology, and two small-business grants from NIH.

Other support: $37.5 million in financing from several venture groups, including Versant Ventures, Abingworth Management, Technogen Associates, Schroder Ventures, Frazier & Co, MPM Asset Management, and CMEA Ventures.

Technology: Quantum dots are nanocrystals of semiconductor material that glow in a range of colors, depending on size. Coated with DNA sequences complementary to those they're detecting, they glow in distinctive colors upon binding with the target sequence. Several tests can be conducted simultaneously on the same sample, using different sizes of crystals.



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