Product Line or Service

Light-powered microchips smaller than a pinhead have been developed for use in identifying DNA in clinical samples, in finding and characterizing defective genes, to aid in the production and tracking of pharmaceutical drugs (combinatorial chemistry) and related products and as a simple and effective means of tracking industrial products or commodities. The microchips are read using a flow fluorometer capable of reading both fluorescence and radio frequency (RF) transmissions from the microchip.

Technology/Proprietary Rights

Methods to detect mutated nucleic acids of medical diagnostic significance are anticipated to be among the most rapidly growing techniques used in medical diagnostics by the early twenty-first century. While our understanding of the underlying genetic and biochemical mechanisms is growing rapidly, due to the human genome program, our ability to rapidly and inexpensively determine relevant DNA sequence information from any given individual is lagging behind. This has produced an enormous need for high-throughput, sensitive and specific DNA methods in order to prevent a critical bottleneck in drug discovery, federal approval and development of complex DNA diagnostics. 

PharmaSeq’s revolutionary technology employs a tiny integrated circuit termed a microtransponder, commonly called a microchip. This miniature RF transmitter, 250 microns on each side, stores information in its memory that identifies the genetic sequence of an attached DNA oligonucleotide probe. Specific nucleic acid sequences in a biological specimen are found by reacting fluorescein labeled specimen nucleic acid with separate microchips, each carrying different (unique) oligonucleotide probes. A fluorometric scanner then measures the fluorescent signal generated by hybridized specimen nucleic acid that has attached to the probe on the microchip. When multiple probes (multiple microchips) are employed, the reader can identify which microchip is involved in the reaction by laser activation of the microchip’s electronic memory. Thus, a single specimen nucleic acid from thousands of sequences can be positively identified. Recently, the Company reported the successful design and manufacture of a fully-functional microchip.

PharmaSeq is developing a novel DNA detection system that will accurately detect and differentiate up to 10,000 or more different species of DNA sequences in a single microchip assay. This “multiplex” feature makes the microchip technology ideal for screening assays for several genes at once. The detection of several genes, gene fragments or a genetic mutation is a typical requirement in medicine and research. DNA analysis technology is recognized as a vital component of the nation’s future economic health and competitiveness. Methods currently under study include nucleic acid array techniques. PharmaSeq’s microchip detection system offers superior sensitivity, speed and selectivity and possesses the flexibility to be upgraded with additional oligonucleotide probes. It also allows the use of relatively few probes (<100) at low cost in an assay that does not require a high multiplex level or expensive and unique equipment. The assays are configured similarly to current diagnostic assays and are manufactured through standard biochemical procedures. Manufacturing cost a diagnostic test using 1,000 probes is estimated to be about that of immunoassays currently on the market. 

PharmaSeq’s novel microchip-based assay offers three-dimensional (3D) arrays of DNA probes, a significant improvement over standard two dimensional (2D) assays. Configuration of transponders in the test tube can be considered a 3D array of DNA probes on a solid phase. Nucleic acid probes are indexed, not by standard 2D coordinates of the element on a flat surface, like current glass slide arrays, but by a unique serial number encoded in the microchip memory. This 3D array is analyzed as a linear string of solid-phase particles rapidly passing through the flow chamber of a reader. 

Future applications of the technology include multiplex sandwich immunoassays (antibody could be deposited on the device and specific antigen in the sample detected). Also, donor blood could be quickly and accurately tested for HIV, HTLV, hepatitis B and C simultaneously in a single vessel, using the same specimen. 

PharmaSeq has been granted six U.S. patents covering multiple aspects of the technology. These include: 1) “Electronically-indexed solid-phase assay for biomolecules, ”US Patent #5,641,634; 2) “Method of determining the sequence of nucleic acids employing solid phase particles carrying transponders,” #5,736,332); 3) “Screening of soluble chemical compounds for their pharmacological properties utilizing transponders,” #5,981,166; 4) “Multiplex assay for nucleic acids employing transponders,” #6,001,571; 5) “Method of determining the sequence of nucleic acids employing solid phase particles carrying transponders,” #6,046,003), and; 6) “Multiplex assay for nucleic acids employing transponders,” #6,051,377. Several US patent applications are pending and international patent applications have been published. 

Market Opportunities

PharmaSeq has developed light-powered microchips in direct response to the need for faster, easier and more accurate development of pharmaceuticals and DNA diagnostic tests. The rapid expansion of combinatorial chemistry methods in drug discovery and target validation has produced an enormous need for technologically advanced, ultra-high-throughput assays. PharmaSeq’s light-powered microchip technology is expected to become a primary tool for assay development involving molecular recognition. The potential benefit of applicable technologies to the US economy is enormous. Recent estimates indicate that the market size for DNA probe diagnostic assays alone will be approximately $1 billion annually by the year 2002 in the US and twice that amount worldwide.

The microchip technology has broad utility over an even larger number of medical and nonmedical markets. These include medical immunodiagnostics, and identification and tracking of valuable products or precious materials and commodities. The technology is utilizable in high technology as well as in low technology applications, such as inventory control and theft prevention.

Competition

PharmaSeq is in a unique position in that it is the only company that has developed microchip technology for use in three dimensional array research. Only three other companies are in this area and they utilize fluorescent microparticles (latex beads) which have serious limitations. These companies are Illumina, Luminex and Lynx. However, the market in 2D arrays is crowded; over 100 companies competing directly or indirectly for customers. Two well-known companies in the 2D array market are Affymetrix and Hyseq. Many of these firms use specially silated glass upon which to affix oligonucleotides for research and diagnostics. The process and instruments are very costly. We believe that many customers will move away from standard 2D arrays to the faster, less expensive 3D microchip array system developed by PharmaSeq.