Lab-on-a-chip offers quick, sensitive and selective chemical analysis

A powerful new portable chemical analysis device that fits in the palm of a hand is being developed by the Department of Energy’s Sandia National Laboratories in Livermore, Calif., and was presented at the annual meeting in March of the American Chemical Society in San Francisco.
   People have been talking about this for a long time, said chemist and presenter Christopher Bailey, who works at Sandia’s Livermore, Calif. lab. "It integrates all the pieces."
   Sandia researchers demonstrated the device’s capabilities by analyzing a complex mixture of explosives. A chemical signature — or fingerprint — is created by separating constituents with chromatography, a process of moving the mixture through separate channels containing a variety of materials. The materials retain constituents to different extents, so they appear sequentially in separate batches at the end of the channel. From an initial mixture injected manually into a resevoir, the system automatically distributes a fraction of a droplet (a tenth of a nanoliter) to channels thinner than human hair. Within a minute, a small display screen flashes the name and quantity of the components. The technique detects compounds at the part-per-billion level. This process, which involves shrinking and knitting together disparate systems, replaces standard chemical analysis methods normally performed with bulky equipment on a laboratory countertop.

Lab in a pea pod — three principal components of Sandia’s integrated micro chem lab are small enough to fit easily inside a snow pea pod.

   Quick, sensitive and selective chemical analysis on a chip is expected to become affordable and widespread in the near future. Researchers envision automated field-portable systems producing results in real time that could sniff out land mines, signal food quality, check environmental safety for emergency responders who suspect chemical or biological hazards, detect pollutants near their source, perform medical diagnostics at the bedside, screen new pharmaceutical drug candidates or optimize industrial processing.
   The hand-held chemical device includes a compact power source and solid-state relays that regulate and switch energy drawn from camera batteries. Built-in lasers and photodiodes read results in each of three channels.
   Results are analyzed by an internal microprocessor, which also automates the separation. To program the microprocessor, users toggle through a menu of commands using four buttons on a touch pad.
   Designing the interface between the microfabricated components and the macroscopic world was just one of the challenges that the team faced, Bailey said. A second unit designed to safely spot trace indicators of biological toxins is in development.
   Sandia is a multiprogram Dept. of Energy laboratory, operated by a subsidiary of Lockheed Martin Corp. Sandia has major research and development responsibilities in national security, energy and environmental technologies.

HIPAA conference speakers outline the challenges ahead
The two-day 2000 Health Insurance Portability and Accountability Act Conference opened on March 13th in Washington, DC with remarks from Bill Braithwaite, senior advisor, Health Information Policy, for the U.S. Department of Health and Human Services.
   Braithwaite began the conference with an overview of the HIPAA regulation and an outline of the implementation challenges. He made several key announcements, including the delay of the security regulations until the third quarter of this year and the release of transaction and code sets from HHS by the end of June 2000.
   Representatives from the Health Care Financing Administration (HCFA) provided an overview on code sets, information security and identifiers. During the afternoon, conference attendees were involved in sessions on HIPAA issues, including information security, implementation and compliance.
   The conference’s closing session, "National Outlook on Privacy-Confidentiality Panel," featured Paul Tang, M.D., of the Palo Alto Medical Clinic and Epic Research Institute, Palo Alto, Calif. Tang focused on the issue of privacy and laid out four goals for privacy protection: individually identifiable information used only for purposes under which it was acquired; patient-care decisions based on complete, accurate information; access to individually identifiable health information based on a need to know basis; and everyone accountable for handling confidential information properly.
   Tang also discussed the main issues of the HHS Privacy Notice of Proposed Rule Making (NPRM), and provided recommendations on each issue, including electronic versus paper media, minimum necessary provision, business partner contracts, ‘opting out,’ and federal preemption. Tang said a potential problem area could be e-health sites that are not covered by HIPAA.
   Other sessions on the closing day of the conference included speakers on how to interpret and understand the regulations, how to formulate an appropriate response to the regulations, and how the legal issues surrounding HIPAA compliance work.
   The 2000 HIPAA conference was sponsored by the Joint Healthcare Information Technology Alliance (JHITA), which is comprised of the American Health Information Management Association (AHIMA), American Medical Informatics Association (AMIA), Center for Healthcare Information Management (CHIM), College of Healthcare Information Management Executives (CHIME), and Healthcare Information and Management Systems Society (HIMSS). Other sponsors were the Computer-based Patient Record Institute (CPRI), American Hospital Association (AHA), and Health Forum of the AHA.

PCR testing may detect low levels of Hep-B virus in plasma products missed by serology
PCR screening may help identify the presence of hepatitis B virus in plasma that has already cleared serology screens for hepatitis B surface antigen, according to data presented to the U.S. Food and Drug Administration Blood Products Advisory Committee by Aventis Behring of Strasbourg, France.

Members of the quality assurance team at Aventis Behring’s Kankakec, Ill., facility inspect units of the company’s life-saving therapies.

   Investigational PCR screening is designed to detect very low levels of viruses by testing for viral DNA and RNA. PCR may detect viruses at an earlier stage than traditional screening methods, such as serology. Serology screening detects either virus proteins or antibodies to virus proteins compared to the detection of virus genetic material.
   The data presented included 3,250,000 plasma samples, which underwent nucleic acid testing using Aventis, Behring’s proprietary PCR technology, following negative results for hepatitis B surface antigen. Investigators found that 62 samples from 42 donors contained the virus. The plasma units for these donations were subsequently removed from the plasma pool for the manufacturing of final plasma-derived products.

Acquisitions and growth spur Bayer sales 10 percent in 1999
Bayer Corp.’s sales increased 10 percent in 1999 to $8.9 billion with about half the growth due to recent acquisitions, including the December 1998 acquisition of Chiron Diagnostics.
   Further growth and increased profits are expected in 2000 and beyond as the company continues to integrate recently acquired businesses and expand its aggressive investment in capital expenditures and research and development, according to a statement from Bayer Corp. President and CEO Helge H. Wehmeier at the company’s annual news briefing.
   “Bayer Corp. became stronger, more tightly focused, better positioned for growth and more closely attuned to our customer’s current and future needs during 1999, thanks to acquisitions, investments and infrastructure improvements that make us more efficient and easier to do business with,” Wehmeier said. As evidence of the growth, Wehmeier cited an increase in sales per employee from $253,000 in 1992 to $402,000 in 1999. During the same period, the company saw sales increase almost $4 billion. Growth in 2000 is expected to remain strong. Sales in the first two months of the year have increased at a double-digit pace.
   Bayer’s healthcare sector experienced an overall growth rate of 21 percent in 1999 with sales from its diagnostics business expanding 43 percent, boosted by the Chiron acquisition.

Diagnostic Deals

La Jolla Diagnostics Inc. (La Jolla, Calif.), and Meridian Diagnostics (Cincinnati, Ohio) announced an agreement for an undisclosed cash payment and future royalties for a rapid blood test for active tuberculosis from the DiagnosTech subsidiary of La Jolla Diagnostics.    The three-minute test uses a combination of three specialized Mycobacterium tuberculosis antigens that react with serum from persons having active TB. The test distinguishs TB infection from active disease making it useful in selecting the appropriate therapy.    Bio-Rad Laboratories (Hercules, Calif.) has signed a five-year single-source contract with the Tenet/BuyPower HealthSystem to provide quality control products for its member clinical diagnostics laboratories. Tenet, which is based in Santa Barbara, Calif., owns or operates 113 acute care hospitals in 17 states. Bio-Rad will supply the Tenet and BuyPower member hospitals with general and special chemistry controls for clinical diagnostic testing and its Unity family of QC software resources.    Medical technology company Biomerica, Inc. (Newport Beach, Calif.) has signed a two-year exclusive agreement with Sentinel CH.s.r.l., an Italian medical diagnostic product distributor based in Milan. Sentinel will market and distribute Biomerica’s Allerquant Med90 food allergy kit throughout Italy. The agreement calls for Sentinel to make guaranteed minimum purchases of the Med90 kit product, a test that can detect if a patient is allergic to any one of 90 different foods from a few drops of blood. It determines allergies to foods by measuring the relative amount of antibodies in the blood.    Biomerica’s Allerquant test will be marketed in Italy to allergists, homeopathic practitioners, and reference laboratories that conduct allergy testing.    Xtrana Inc. (Denver) has received a Small Business Innovation Research (SBIR) Phase I grant from the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) to develop a nucleic acid-based detection system for Chlamydia trachomatis.    The amplification strategy used in the test is isothermal, eliminating the need for equipment such as thermocyclers. Test results will be available before the patient leaves the facility, which will allow for immediate treatment of infected individuals.    In addition to high sensitivity, the Xtrana test detects RNA from chlamydia and can therefore be more specific to live organisms than DNA-based tests or antibody/antigen tests.    Dublin-based Trinity Biotech plc has acquired MarDx Diagnostics Inc. (Carlsbad, Calif.) for a consideration of $4 million. The acquisition will be accrue immediately to Trinity’s earnings.    The principal product of Western blot manufacturer MarDx is a test for Lyme disease. Trinity’s worldwide distribution network and existing presence in the Lyme disease screening market position it well to expand sales of the MarDx products.    CompuCyte Corp. (Cambridge, Mass.) and Tokyo-based Olympus Optical Co., Ltd. have entered into a three-year distribution agreement, effective Jan. 1, 2000. Under the agreement, Olympus will sell CompuCyte’s LSC Laser Scanning Cytometer product line in the Asia/Pacific market, including Japan, Korea, Hong Kong, Thailand, Taiwan, the Philippines, China, India, Malaysia, Singapore, Indonesia, Australia, and New Zealand.   Olympus also will provide training and customer service in these countries.    Introduced in 1996, CompuCyte’s patented cell analyzer LSC is used in a range of research applications including drug discovery, cell biology and cancer research. It uses a computer-guided laser beam to analyze biological samples.    Digene Corp. (Gaithersburg, Md.) announced that Unilab Corp., (Tarzana, Calif.) a large provider of clinical lab testing in California, will offer the Digene Hybrid Capture II HPV Test. Unilab has regional core reference laboratories in Los Angeles, San Jose and Sacramento and performs more than 1,000 clinical tests daily including molecular diagnostic tests for HIV, chlamydia, gonorrhea and HPV. Unilab serves office-based physicians in private, group and clinic settings, as well as hospitals, corporations and HMOs.    Qiagen N.V. (Venlo, the Netherlands) has announced plans to set up a wholly-owned subsidiary in Italy, which will allow the company to address the Italian market directly through its own sales force. It is intended to increase the company’s presence and strategic position in the marketplace. The market potential in Italy for molecular biology-related products is approximately two percent of the worldwide market potential, according to a Qiagen spokesperson.    Hemagen Diagnostics (Waltham, Mass.) has received clearance from the Food and Drug Administration to begin marketing four of its clinical chemistry reagents for use on the Roche Diagnostics Cobas Mira chemistry analyzer. As part of the previously announced agreement with Roche, Hemagen’s Raichem Division agreed to seek FDA clearance for four reagents to work on the Roche analyzer. The four reagents are Total Protein, Albumin, Calcium, and GGT.    Bio Plexus, Inc. (Vernon, Conn.), which designs, develops and manufactures safety medical needles and products under the Punctur-Guard, Drop-It, and Punctur-Guard Revolution brand names, has announced a distribution agreement with McKessonHBOC Medical Group of Richmond, Va. The agreement allows McKessonHBOC to purchase and distribute Punctur-Guard products to more than 85,000 healthcare providers nationwide.    The parent company of Sigma Diagnostics, Sigma-Aldrich Corp., has received the “E-Commerce Innovator of the Year” award by Network World. The award recognizes the company’s endeavors in integrating its back-end order processing system with its web e-commerce system, “Pipeline.”    Commercial and clinical trial packaging supplier Sharp (Conshohocken, Pa.) and INC Research (San Diego), a specialized contract research organization managing central nervous system and pain clinical trials, have announced plans to cross-market their services. As a result, INC Research pharmaceutical and biotechnology customers will be able to access Sharp clinical material services, which include packaging, assembly, distribution, returns, and destruction. Sharp will refer its packaging clients who require CNS and pain clinical trials services to INC Research.    As part of the joint marketing program, the companies will collaborate on clinical sales and marketing efforts.    LabCorp (Burlington, N.C.) has entered into an agreement with San Diego-based PoisonLab, Inc. to acquire all of its stock. PoisonLab is an occupational substance abuse and clinical toxicology testing business. Terms of the agreement were not disclosed.    PoisonLab, a Substance Abuse and Mental Health Services Administration-certified reference toxicology lab, provides forensic drug testing and clinical therapeutic drug monitoring. The lab can accommodate more than 7,500 specimens a day and offers more than 400 specialty tests. The acquisition expands LabCorp’s specialty testing services in the West, and will complement its Center for Occupational Testing in North Carolina and additional testing sites in Florida, New Jersey, Tennessee and Texas.    The Board of Directors of DiaSys Corp. (Waterbury, Conn.), which designs, develops, manufactures and distributes urinalysis, microbiology and cytology equipment, has declared a 2 for 1 stock split of its common shares. The stock split is effective for all shareholders of record as of March 8, 2000.    Abbott Laboratories (Abbott Park, Ill.) has reached an agreement with the Federal Trade Commission resolving issues related to an agreement it made with Geneva Pharmaceuticals, regarding Hytrin (terazosin hydrochloride) patent litigation. Abbott’s agreement with the FTC contains no admission of wrongdoing and does not include any payments to the government. Hytrin is an alpha blocker indicated for hypertension and benign prostatic hyperplasia.    Under the FTC agreement, Abbott, when it is the New Drug Application (NDA) holder, agreed to refrain from making agreements with Abbreviated New Drug Application (ANDA) first filers that restrict their rights with respect to market exclusivity. Under the same circumstances, Abbott also agreed to refrain from reaching agreements which prohibit the sale of drugs which are included within the ANDA and are not the subject of patent infringement actions. In addition, Abbott agreed it would not enter into an agreement that restricts and infringes from entering the market during litigation, unless the parties petition the court, provide notice to the FTC, and are granted a stipulated preliminary injunction. Abbott also agreed to provide notice to the FTC of any agreement in which the ANDA first filer agrees to refrain from selling any drug product.    On April 1, 1998, Abbott and Geneva reached an agreement under which Geneva would not market its FDA-cleared generic terazosin hydrochloride products until resolution of the pending litigation between the parties. In April 1999 the FTC notified Abbott that it was investigating the agreement with Geneva. On August 12, 1999 Abbott and Geneva terminated their April 1, 1998 agreement, and on August 13, 1999, Geneva entered the market with its product.    Balance manufacturer Ohaus Corp. (Florham Park, N.J.) recently received the 1999 Outstanding Supplier Quality Award from Fisher Scientific. The award, which was presented at Fisher’s national sales meeting, recognizes the company’s ability to meet and exceed Fisher’s performance expectations across numerous business areas.    Advanced Photonix, Inc. (Camarillo, Calif.), developer and manufacturer of large avalanche photodiodes announced a $440,000 agreement to provide LED/detector modules to bioMerieux, Inc. (St. Louis) for use in its next generation microbiology testing system, the Vitek 2 System.    eMD.com, a business-to-business Internet healthcare subsidiary of BioShield Technologies Inc. (Atlanta) has signed a letter of intent to acquire all the assets of LabAmerica Inc., a specialty Internet company positioned to facilitate confidential medical lab testing at more than 1,400 locations nationwide. Terms of the agreement include a combination of cash, future eMD.com common shares and warrants.    LabAmerica’s service will be integrated as an enhancement to eMD.com’s point-of-care medication management and charting system. It will be a web-based, nationwide lab testing service where consumers can order individual tests. Through two sites, LabAmerica will be able to help patients anonymously order a variety of blood and urine tests. Companies also can use the service to arrange employee drug screenings, which can streamline the process and lower lab costs by overcoming the need for a physician’s direct order. Confidential lab results, available within 48 hours, can be accessed through a secure, password-protected application on LabAmerica’s Web site and/or the My Medical History application. If requested by the patient, the results can be sent directly to the individual’s physician.    Merck KGaA has announced a strategic refocusing of its Laboratory Business, effective July 1, 2000. The global Laboratory Distribution Business, consisting of the Merck Eurolab Group, Zaventem, Belgium, and VWR Scientific Products Corp., West Chester, Pa., will combine to become one independent company with headquarters in the United States.

Award finalists recognized for design innovation
Finalists in the Medical Design Excellence Awards (MDEA) 2000 competition include two in vitro diagnostic products. The program recognizes product innovation, design and engineering excellence, end-user benefit, and cost-effectiveness in manufacturing and healthcare delivery.
   The awards program is organized by Canon Communications LLC and sponsored by Medical Device & Diagnostic Industry magazine. The finalists, in 10 medical product categories, were determined following a review and evaluation of submitted entries by a nine-member jury with expertise in biomedical engineering, human factors, industrial design, medicine, nursing, diagnostics and medical packaging.
Within the In Vitro Diagnostics category, the MDEA finalists included AtLast, a blood glucose monitoring system from Amira Medical, Scotts Valley, Calif., that eliminates diabetic’s use of fingersticks. The device creates a small break in the skin of the arm or thigh, which can be less sensitive than the fingertips because they have fewer nerve endings. A press-and-release of the device draws blood to the surface where the system collects and reads it. According to Karen Drexler, president and co-founder of Amira, the AtLast system draws a small blood sample to the test strip through a micro-capillary tube, providing results in under 15 seconds.
The other finalist, the Careside Analyzer from Careside Inc., Culver City, Calif., is a near-patient blood testing system. It provide results in less than 15 minutes and holds up to six cartridges of a single patient’s blood at one time. Patient sample and reagent are mixed together inside the disposable cartridge.
   The winners will be announced at the MD & M East Exposition, June 6-8, 2000, in New York City.