CIPH Part II:
Another approach appears to take SQNM's idea of genomics via chip-based MS and applies it to proteomics. From some locals:
>>Desorption/ionization on silicon (DIOS): A diverse mass spectrometry platform for protein characterization
John J. Thomas*, Zhouxin Shen , John E. Crowell , M. G. Finn*, and Gary Siuzdak*,§
* Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; Mass Consortium Corporation, San Diego, CA 92121; and Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093-0314
Communicated by Julius Rebek, Jr., The Scripps Research Institute, La Jolla, CA, February 12, 2001 (received for review December 22, 2000)
Since the advent of matrix-assisted laser desorption/ionization and electrospray ionization, mass spectrometry has played an increasingly important role in protein functional characterization, identification, and structural analysis. Expanding this role, desorption/ionization on silicon (DIOS) is a new approach that allows for the analysis of proteins and related small molecules. Despite the absence of matrix, DIOS-MS yields little or no fragmentation and is relatively tolerant of moderate amounts of contaminants commonly found in biological samples. Here, functional assays were performed on an esterase, a glycosidase, a lipase, as well as exo- and endoproteases by using enzyme-specific substrates. Enzyme activity also was monitored in the presence of inhibitors, successfully demonstrating the ability of DIOS to be used as an inhibitor screen. Because DIOS is a matrix-free desorption technique, it also can be used as a platform for multiple analyses to be performed on the same protein. This unique advantage was demonstrated with acetylcholine esterase for qualitative and quantitative characterization and also by its subsequent identification directly from the DIOS platform.<<
This might be the future, but it's a long ways from commercialization. So I feel fairly confident that CIPH is the market leader, and has the cash to acquire competing/complementary technologies/companies. I cannot say if the technologies referrenced will overtake CIPH or not, doubt anyone can now.
How about current technologies refined? Rueddi Aebersold and others have been refining the use of MS and MS/MS for proteomics. As I've noted before, he has said that the near future in this area will involve more separation steps prior to MS. While that will help throughput and sensitivity, it'll increase cost (all those columns and digesters, etc., not to mention the ICAT reagents (an ICAT kit can cost over a grand)).
Quantitative proteomic analysis using a MALDI quadrupole time-of-flight mass spectrometer.
Griffin TJ, Gygi SP, Rist B, Aebersold R, Loboda A, Jilkine A, Ens W, Standing KG.
Department of Molecular Biotechnology, University of Washington, Seattle 98195-7730, USA. tgriffin@systembiology.org
We describe an approach to the quantitative analysis of complex protein mixtures using a MALDI quadrupole time-of-flight (MALDI QqTOF) mass spectrometer and isotope coded affinity tag reagents (Gygi, S. P.; et al. Nat. Biotechnol. 1999, 17, 994-9.). Proteins in mixtures are first labeled on cysteinyl residues using an isotope coded affinity tag reagent, the proteins are enzymatically digested, and the labeled peptides are purified using a multidimensional separation procedure, with the last step being the elution of the labeled peptides from a microcapillary reversed-phase liquid chromatography column directly onto a MALDI sample target. After addition of matrix, the sample spots are analyzed using a MALDI QqTOF mass spectrometer, by first obtaining a mass spectrum of the peptides in each sample spot in order to quantify the ratio of abundance of pairs of isotopically tagged peptides, followed by tandem mass spectrometric analysis to ascertain the sequence of selected peptides for protein identification. The effectiveness of this approach is demonstrated in the quantification and identification of peptides from a control mixture of proteins of known relative concentrations and also in the comparative analysis of protein expression in Saccharomyces cerevisiae grown on two different carbon sources.<<
Both are an improvement over the current slow, cheap standards of Western immunoblotting and SDS-PAGE, a gel electrophoresis technique described here
uct.ac.za
By contrast, check this complete article on an application of SELDI:
aem.asm.org
Many, if not most, of CIPH's competitors are private, do lots of other things, or are subsidiaries. This is the best pure play available, trading near cash and book in lock-up hell. It's readers are big-ticket items subject to the current capex slowdown, but the chips and such are consumables. So the fact that CIPH & BCOR already have an installed base in this setting confers an advantage to them for the intermediate term, IMO. I could be wrong about the legal gravity of the Hutchens suit, and would appreciate any needed correction from those more expert. But my read is that the royalties were capped at $500K/yr each for the two technoligies at issue, so this ought to be a small thing.
All in all, I think CIPH is compelling at these levels. The capex slowdown should ease in the next two or three Qs. At the rate Hutchens is going, he'll be done selling by then, as will most of the VC. Those that checked the unlock know that there is a large overhang. But it's being worked through pretty fast. CIPH seems pretty resilient here, consistently bouncing back quickly when it gets under $5. My strategy for CIPH would be to accumulate under $5, pending major news. And I don't expect any for a while, so I'd think this could trade on the technicals and the dynamics of being in BLUE H with its own personal demon.
Accordingly, BLUE HP will target 500 shares for $4.90.
Comments are invited, as always. Particularly if someone with legal background would like to handicap the CIPH/LumiCyte contest or comment on it's magnitude.
Taking off tomorrow, and will be gone for a full week. However, I might be able to check in Thursday and beyond. At the moment, CIPH, 500 @ $4.90 and KOSN 1000 @ $7.50 are my two targets. Perhaps Tom or someone can let me know if those trades would have executed while I'm out of touch. I'd appreciate it.
Cheers, Tuck |
