> **NIH Update of Activities for the\
> Executive Order 13329: *Encouraging Innovation in Manufacturing***

**(FY 05 Submittal)**

***July 28, 2006***

**Introduction:** On February 26, 2004, Executive Order (EO)
[13329](http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2004/pdf/04-4436.pdf)
was signed by President George W. Bush requiring SBIR/STTR agencies, to
the extent permitted by law and in a manner consistent with the mission
of that department or agency, to give high priority within the SBIR and
STTR programs to manufacturing-related research and development (R&D).
"Manufacturing-related" is defined as "relating to manufacturing
processes, equipment and systems; or manufacturing workforce skills and
protection."

E.O. 13329 is intended to help ensure that Federal agencies properly and
effectively assist the private sector in its manufacturing innovation so
as to sustain a strong manufacturing sector in the United States economy
by advancing innovation, including innovation in manufacturing, through
small businesses.

As noted at the SBIR Program Managers meeting on January 11, 2005, the
annual reporting requirements were changed in the following way:
**[Agencies are no longer required to develop or report the statistics
on their manufacturing-related projects]{.underline}.** Instead, SBA
will develop a report on the E.O. using the annual SBIR award data that
Agencies must report to SBA for the SBIR Annual Report to Congress. SBA
provided new guidance to the agencies on June 16, 2006 regarding the
submission of the FY 2005 report, due to SBA by August 1, 2006.

1.  Examples of manufacturing-related NIH SBIR/STTR projects

+---------------------------------------------------------------------+---+
| **CFD Research Corporation** (Information Posted/Updated on         |   |
| 02/01/2005)\                                                        |   |
| 215 Wynn Drive\                                                     |   |
| Huntsville, AL  35805\                                              |   |
| \                                                                   |   |
| **Contact:**    Ashok K. Singhal\                                   |   |
| **Phone:**      256-726-4841\                                       |   |
| **Fax:**          256-726-4806\                                     |   |
| **E-mail:**      <aks@cfdrc.com>\                                   |   |
| **Web Site:**  [http://www.cfdrc.com](http://www.cfdrc.com/)        |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  Development of Improved Hemodialysis Catheter   |   |
| Designs                                                             |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  SBIR Phase I #1R43DK53114-01, SBIR Phase II  |   |
| #1R44DK53114-02                                                     |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| CFD Research Corporation has developed and patented a novel and     |   |
| significantly improved hemodialysis catheter (Patent \# US          |   |
| 6,409,700 B1). This fixed tip catheter combines ease of insertion   |   |
| with high flow and very low recirculation, delivering the ultimate  |   |
| high efficiency dialysis. The catheter has been designed and        |   |
| optimized with extensive use of advanced computer simulations       |   |
| (computational fluid dynamics (CFD) and coupled fluid-structural    |   |
| interactions) and a complimentary series of experimental            |   |
| investigations.                                                     |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  Catheter, hemodialysis, access recirculation,       |   |
| suction pressure, hemolysis.                                        |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| The developed catheter has been specifically designed and tested    |   |
| for hemodialysis applications. Its uniquely engineered tip provides |   |
| outstanding performance with the following characteristics:         |   |
|                                                                     |   |
| \- Improved functionality by reductions in occlusion potential,     |   |
| recirculation, and arterial suction pressure.                       |   |
|                                                                     |   |
| \- Maximum arterial blood flow when the catheter tip contacts the   |   |
| vessel sidewall.                                                    |   |
|                                                                     |   |
| \- Reduced red blood cell damage.                                   |   |
|                                                                     |   |
| \- Reduced blood clotting and potential side effects.               |   |
|                                                                     |   |
| \- Improved ease of insertion.                                      |   |
|                                                                     |   |
| Benefits to dialysis patients will include increased safety and     |   |
| comfort level, and possibly a short therapeutic time.               |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| This SBIR program and other NIH funding have enabled CFDRC to       |   |
| broaden its expertise in developing biomedical devices using        |   |
| coupled virtual prototyping and experimental approach. This         |   |
| expertise has been applied to develop other devices and obtain more |   |
| patents, leading to increased revenues and profitability of the     |   |
| company.                                                            |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| CFDRC patented the new design and, after investigation of several   |   |
| biomedical companies, selected Spire Biomedical Inc. as a           |   |
| commercialization partner for this product. CFDRC granted an        |   |
| exclusive license to Spire, with provisions for: (a) milestone      |   |
| payments, e.g. with FDA approval and launch of product, and (b)     |   |
| royalties based on net sales.                                       |   |
+---------------------------------------------------------------------+---+
| **Other Comments Related to Company\'s Success Story:**\            |   |
| The product was launched in late 2004 in St. Louis, Missouri at the |   |
| American Society of Nephrology Annual Conference. The catheter      |   |
| sales revenues are expected to be tens of millions of dollars. It   |   |
| is a very competitive market space, and thus will require           |   |
| significant sales effort. The performance of the developed catheter |   |
| is significantly better than the other catheters currently used.    |   |
| The initial feedback from leading nephrologists and vascular        |   |
| surgeons is very encouraging, and sales are expected to grow        |   |
| steadily.                                                           |   |
+---------------------------------------------------------------------+---+

+---------------------------------------------------------------------+---+
| **Transonic Systems, Inc.** Information Posted/Updated on           |   |
| 08/27/2005\                                                         |   |
| 34 Dutch Mill Road\                                                 |   |
| Ithaca, NY  14850\                                                  |   |
| \                                                                   |   |
| **Contact:**    Cornelis J. Drost\                                  |   |
| **Phone:**      607-257-5300\                                       |   |
| **Fax:**          607-257-7256\                                     |   |
| **E-mail:**      <Cor.drost@transonic.com>\                         |   |
| **Web Site:**  <http://www.transonic.com/>                          |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  A Flowmeter with Telemetry for Chronic Animal   |   |
| Studies                                                             |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  1 R43 HL62079-01A2                           |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| SBIR Phase I funding enabled Transonic Systems, Inc. to develop,    |   |
| validate, and commercialize a new telemeter flowmeter for animal    |   |
| studies. This technology is essential to studying cardiovascular    |   |
| diseases and their genetic causes and treatments.                   |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  Wireless, Transit-Time, Flow, Ultrasound,           |   |
| Bluetooth, Telemetry, Flowmeter, Manufacturing.                     |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| Many physiological studies involve lab animals, and researchers     |   |
| often must measure arterial blood flow to properly evaluate a drug  |   |
| or device\'s safety and effectiveness. For example, drugs used to   |   |
| prevent heart disease are tested in pigs, while many artificial     |   |
| heart prototypes are tested in dogs and cows.                       |   |
|                                                                     |   |
| However, traditional measurement technology requires that           |   |
| researchers monitor implanted flow sensors with wired tethers       |   |
| connecting the animal to a bench-top flowmeter. This experimental   |   |
| setting can stress the animal; alter the blood flow; and requires   |   |
| more supervision to assure humane conditions.                       |   |
|                                                                     |   |
| With NIH/NHLBI Phase-I SBIR research support and corporate internal |   |
| development funds, Transonic Systems developed a miniaturized       |   |
| low-power flowmeter board that was small enough to be carried by    |   |
| laboratory animals, and that maintained the accuracy of benchtop    |   |
| flowmeters. This is the first step towards the ongoing SBIR         |   |
| Phase-II goal of a fully implantable telemetered flowmeter.         |   |
|                                                                     |   |
| Transonic Systems commercialized the Phase-I device as a key        |   |
| component in the PhysioGearTM I wearable telemetered flowmeter      |   |
| system for laboratory animals. Developed in collaboration with      |   |
| Telemetronics Biometry, this battery-powered system will operate    |   |
| standard Transonic implantable flow probes, and uses a Bluetooth    |   |
| wireless link to telemeter flow readings to a monitoring PC.        |   |
|                                                                     |   |
| This system promises to revolutionize safety pharmacology, medical  |   |
| device testing, and academic research. The new Transonic hardware   |   |
| will allow studies to proceed faster and with fewer animals, since  |   |
| the investigator can now monitor organ blood flow in animals during |   |
| the full course of a disease/treatment study. For product           |   |
| information and pictures of the commercialized hardware, see the    |   |
| following URL: <http://www.transonic.com/physiogear.shtml>          |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| SBIR Phase I & II funding enabled Transonic Systems, Inc. to        |   |
| develop, validate, and commercialize a new telemetered blood flow   |   |
| monitoring systems for free-roaming animal studies. This technology |   |
| is essential to medical studies of diseases, their genetic causes,  |   |
| and treatments. This new product is the fourth Transonic product    |   |
| developed and commercialized under NIH SBIR program. Previous       |   |
| commercialized products include the HD01 Hemodialysis Monitor, the  |   |
| 0.5PSB and 0.7PSB Mouse blood flowprobes and 420-series flowmeter,  |   |
| and the AngioFlow angioplasty flow monitoring catheter. Around 25%  |   |
| of our current \$12 million yearly sales include SBIR-developed     |   |
| technologies.                                                       |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| After the Phase-I research completed in March 2002, Transonic       |   |
| Systems teamed with TeleMetronics Biometry to develop the           |   |
| PhysioGear I telemeter flowmeter. This collaboration married the    |   |
| Phase-I miniaturized flowmeter board with a battery subsystem and   |   |
| BlueTooth wireless communications to create the PhysioGear-ITM      |   |
| system.                                                             |   |
|                                                                     |   |
| The system went into beta testing with three university sites in    |   |
| March 2004, and product sales began July 1st, 2005.                 |   |
|                                                                     |   |
| Transonic Systems now manufactures the PhysioGearTM-I at company    |   |
| headquarters in Ithaca, NY. Domestic sales and marketing are        |   |
| handled by Transonic-Ithaca , and international sales are handled   |   |
| through a worldwide network of Transonic sales representatives.     |   |
+---------------------------------------------------------------------+---+
| **Other Comments Related to Company\'s Success Story:**\            |   |
| At a time when many U.S. manufacturing jobs have been outsourced    |   |
| overseas, worldwide sales of Transonic sensors and meters have      |   |
| created new manufacturing jobs in rural Upstate New York.           |   |
+---------------------------------------------------------------------+---+

+---------------------------------------------------------------------+---+
| **Concordant Rater Systems** (Information Posted/Updated on         |   |
| 01/05/2006)\                                                        |   |
| 6 Beacon St\                                                        |   |
| Suite 205\                                                          |   |
| Boston, MA  02108\                                                  |   |
| \                                                                   |   |
| **Contact:**    Dan DeBonis\                                        |   |
| **Phone:**      617-367-0044\                                       |   |
| **Fax:**          617-507-2423\                                     |   |
| **E-mail:**      <dand@concordantrater.com>\                        |   |
| **Web                                                               |   |
| Site:**  [www.concordantrater.com](http://gra                       |   |
| nts1.nih.gov/grants/funding/sbir_successes/www.concordantrater.com) |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  An Interactive Computer Interview for Mania to  |   |
| Enhance Human Rater Performance                                     |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  R43 MH65796                                  |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| The Interactive Computer Interview (ICI) was developed by CRS for   |   |
| the administration of clinical rating scales. (A provisional patent |   |
| was also issued in 2003).                                           |   |
|                                                                     |   |
| The ICI is computerized interview that simulates a clinician's      |   |
| administration of a rating scale and uses program logic to select a |   |
| sequence of probes and follow-up queries necessary to assign        |   |
| symptom severity ratings.                                           |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  CNS outcomes, Rater Reliability, Clinical Trials,   |   |
| Site Monitoring, Computerized Adaptive Tes, Mental Health, Bipolar  |   |
| Disorder.                                                           |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| The ICI was found to be a well accepted, reliable, and valid method |   |
| for eliciting and assessing manic and depressive symptoms.          |   |
|                                                                     |   |
| There are 3 current uses for the technology: 1. Remote site         |   |
| monitoring in multi center trials to improve rater reliability. The |   |
| ICI computer assessment is paired with live rater assessments on    |   |
| standardized rating scales (YMRS, MADRS, HAMD, HAMA). 2. A stand    |   |
| alone Rater Station ™ system that assesses subjects and generates a |   |
| score for standardized rating scales. 3. A prompted clinical        |   |
| interview, where a human rater uses the ICI to administer a         |   |
| standardized rating scale either live or over the telephone.        |   |
|                                                                     |   |
| The fact that the system can be easily translated makes it an       |   |
| inexpensive, valid option for CNS research in foreign countries and |   |
| bi-lingual communities in the US.                                   |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| The SBIR funding was critical in allowing CRS to conduct an initial |   |
| validity study. The data generated strongly indicated that the      |   |
| product was a reliable and valid method to assess manic and         |   |
| depression patients.                                                |   |
|                                                                     |   |
| The CNS drug and reseach industry were and continue to be very      |   |
| concerned with the issue of rater reliability in multi center       |   |
| trials. The SBIR data provided evidence of a validated approach to  |   |
| reducing rater reliability.                                         |   |
|                                                                     |   |
| Additionally, the SBIR funded a modified CSQ, along with minority   |   |
| and patient focus groups to evaluate the product. These provided    |   |
| valuable feedback and led to further enhancements to the product.   |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| The remote site monitoring system that includes the ICI is now in   |   |
| use in major multi-center CNS pharmaceutical studies.               |   |
|                                                                     |   |
| The Rater Station ™ system is now in use in various investigator    |   |
| initiated studies and proposed for use in multi-center trials.      |   |
+---------------------------------------------------------------------+---+
| **Other Comments Related to Company\'s Success Story:**\            |   |
| Components of the system and the business methods associated with   |   |
| the system were granted provisional US and IPC patents in 2003.     |   |
+---------------------------------------------------------------------+---+
| **Past R&D and/or Sales from this Project:**   \$.5M                |   |
+---------------------------------------------------------------------+---+
| **Estimated Future Annual R&D and/or Sales from this Project:**     |   |
| \$1.5M                                                              |   |
+---------------------------------------------------------------------+---+

+---------------------------------------------------------------------+---+
| **PortaScience, Inc.** (Information Posted/Updated on 06/02/2006)\  |   |
| 1, Whittendale Drive, Suite E\                                      |   |
| Moorestown, NJ  08057\                                              |   |
| \                                                                   |   |
| **Contact:**    Ayoma Finlay\                                       |   |
| **Phone:**      856-231-9922\                                       |   |
| **Fax:**          856-231-9822\                                     |   |
| **E-mail:**      <afinlay@portacheck.com>\                          |   |
| **Web                                                               |   |
| S                                                                   |   |
| ite:**  [http://www.portascience.com](http://www.portascience.com/) |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  A Simple Point-of-Care White Blood Cell Count   |   |
| Test                                                                |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  R44 CA092976-03                              |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| A disposable test strip and hand-held reader combination that can   |   |
| measure white blood cell count in biological fluids quantitatively  |   |
| and with high accuracy.                                             |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  white blood cell, chemotherapy, mastitis,           |   |
| diagnostic, point-of-care, portable.                                |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| This portable and simple-to-use test system has many uses. It       |   |
| allows first time cancer patients to monitor their white blood cell |   |
| counts at home, dairy farmers to screen their cows for mastitis,    |   |
| and veterinarians to check companion animals for infection.         |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| This unique point-of-care technology platform has found many        |   |
| applications besides its original application for cancer patients   |   |
| undergoing chemotherapy. The firm has commercialized the product in |   |
| the dairy market and entered into a licensing agreement for the     |   |
| companion animals market. Within the past 3 years, PortaScience has |   |
| been transformed from an R&D boutique into a product company, with  |   |
| an expected growth rate of over 50% in the next 5 years.            |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| A new division, PortaCheck, was formed to manufacture and market    |   |
| the product to the dairy industry. With only one competitor who     |   |
| sells a product for 10 times the price, PortaCheck was able to make |   |
| significant inroads into a \$20 million dollar market in a short    |   |
| period of time. The licensing agreement for the companion animals   |   |
| application, with an expected launch date in 4th quarter 2006, adds |   |
| an additional potential market of \$15M per year.                   |   |
+---------------------------------------------------------------------+---+
| **Estimated Future Annual R&D and/or Sales from this Project:**     |   |
| \$3.5 M                                                             |   |
+---------------------------------------------------------------------+---+
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **EKOS Corporation** (Information Posted/Updated on          |   | |   |
| |                                                                   |   |
|  08/27/2005)\                                                 |   | |   |
| |                                                                   |   |
|  22030 20th Ave. SE, Suite 101\                               |   | |   |
| |                                                                   |   |
|  Bothell, WA  98021\                                          |   | |   |
| |                                                                   |   |
|  \                                                            |   | |   |
| |                                                                   |   |
|  **Contact:**    Azita Soltani\                               |   | |   |
| |                                                                   |   |
|  **Phone:**      (425) 482-1108\                              |   | |   |
| |                                                                   |   |
|  **E-mail:**      <asoltani@ekoscorp.com>                     |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Project Title:**  In vivo evaluation of ultrasound         |   | |   |
| |                                                                   |   |
|  enhanced lysis.                                              |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Related Award(s):**  5R44HL057739, 1R43HL057739-01,        |   | |   |
| |                                                                   |   |
|  2R44HL057739-02, 1R41HL060468-01, 2R42HL060468-02,           |   | |   |
| |                                                                   |   |
|  4R44HL064434-02                                              |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Technology Developed:**\                                   |   | |   |
| |                                                                   |   |
|  NIH SBIR/STTR funding enabled EKOS Corporation to develop    |   | |   |
| |                                                                   |   |
|  and commercialize ultrasonic infusion systems intended for   |   | |   |
| |                                                                   |   |
|  controlled and selective infusion of physician-specified     |   | |   |
| |                                                                   |   |
|  fluids, including thrombolytics, into the peripheral         |   | |   |
| |                                                                   |   |
|  vasculature.                                                 |   | |   |
| |                                                                   |   |
|                                                               |   | |   |
| |                                                                   |   |
|  The EKOS MicrolysUS® infusion system is a 510K cleared       |   | |   |
| |                                                                   |   |
|  device to treat peripheral arterial occlusion. In addition,  |   | |   |
| |                                                                   |   |
|  this microcatheter has IND approval to participate in Phase  |   | |   |
| |                                                                   |   |
|  II Interventional Management of Stroke (IMS) clinical study  |   | |   |
| |                                                                   |   |
|  to treat ischemic stroke using a combined IV/IA rtPa         |   | |   |
| |                                                                   |   |
|  infusion approach.                                           |   | |   |
| |                                                                   |   |
|                                                               |   | |   |
| |                                                                   |   |
|  The EKOS LysUS® infusion system is also a 510K cleared       |   | |   |
| |                                                                   |   |
|  device to treat peripheral arterial occlusion. This 5 Fr     |   | |   |
| |                                                                   |   |
|  catheter system is available in treatment zone ranging from  |   | |   |
| |                                                                   |   |
|  6 to 50 cm to match a variety of clot lengths and ensure     |   | |   |
| |                                                                   |   |
|  uniform drug/ultrasound energy distribution into the large   |   | |   |
| |                                                                   |   |
|  arterial and venous clots found in the peripheral            |   | |   |
| |                                                                   |   |
|  vasculature. Besides the therapeutic application, EKOS       |   | |   |
| |                                                                   |   |
|  devices have a diagnostic feature to monitor blood flow in   |   | |   |
| |                                                                   |   |
|  occluded lesions during the treatment. The flow sensor       |   | |   |
| |                                                                   |   |
|  feature is based on the catheter ultrasonic element's        |   | |   |
| |                                                                   |   |
|  temperature that will be monitored and displayed on the EKOS |   | |   |
| |                                                                   |   |
|  control unit, which additionally provides power to drive     |   | |   |
| |                                                                   |   |
|  catheter ultrasonic elements. The temperature variations     |   | |   |
| |                                                                   |   |
|  directly correspond to the local flow rate of the blood in   |   | |   |
| |                                                                   |   |
|  the occluded lesion and inform the doctors of the treatment  |   | |   |
| |                                                                   |   |
|  status.                                                      |   | |   |
| |                                                                   |   |
|                                                               |   | |   |
| |                                                                   |   |
|  We believe EKOS infusion catheters provide unique benefit to |   | |   |
| |                                                                   |   |
|  the patient with vascular thrombotic occlusions in the       |   | |   |
| |                                                                   |   |
|  cerebral and peripheral vasculature. In ischemic stroke,     |   | |   |
| |                                                                   |   |
|  accelerated thrombolysis leads to faster restoration of      |   | |   |
| |                                                                   |   |
|  nutrient blood flow to the ischemic tissue and greatly       |   | |   |
| |                                                                   |   |
|  improves the patient's chances of survival with minimum      |   | |   |
| |                                                                   |   |
|  brain damage and reduced burden of neurologic deficits.      |   | |   |
| |                                                                   |   |
|  Potential benefits specific to the infusion of thrombolytics |   | |   |
| |                                                                   |   |
|  with EKOS LysUS® infusion system to treat peripheral         |   | |   |
| |                                                                   |   |
|  arterial occlusion may include a decreased thrombolysis time |   | |   |
| |                                                                   |   |
|  (e.g., decreased time from the start of the procedure to     |   | |   |
| |                                                                   |   |
|  recanalization) due to the improved dispersion and           |   | |   |
| |                                                                   |   |
|  availability of the thrombolytic within the clot. This in    |   | |   |
| |                                                                   |   |
|  turn may reduce the amount of thrombolytic agent used.       |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Key Words:**  Ischemic Stroke, PAO, Infusion catheters,    |   | |   |
| |                                                                   |   |
|  flow sensor, therapeutic ultrasound, manufacturing.          |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Uses of Technology/Products/Service:**\                    |   | |   |
| |                                                                   |   |
|  Peripheral arterial occlusion (PAO) of the lower extremity   |   | |   |
| |                                                                   |   |
|  can cause limb-threatening ischemia and, if left untreated,  |   | |   |
| |                                                                   |   |
|  is associated with a high rate of amputation. The standard   |   | |   |
| |                                                                   |   |
|  of treatment for many years has included open surgical       |   | |   |
| |                                                                   |   |
|  intervention, but this carries a significant risk to life    |   | |   |
| |                                                                   |   |
|  and limb. Attempts to treat PAO by intravenous infusion of   |   | |   |
| |                                                                   |   |
|  thrombolytics have met with low success, and unacceptably    |   | |   |
| |                                                                   |   |
|  high rates of morbidity resulting from serious hemorrhagic   |   | |   |
| |                                                                   |   |
|  events (Kandarpa, 2000; Kessel et al; 2004, Berridge et al,  |   | |   |
| |                                                                   |   |
|  1991). In 1974 Dotter et al (Dotter et al, 1974) introduced  |   | |   |
| |                                                                   |   |
|  the concept of infusion of thrombolytic agents directly      |   | |   |
| |                                                                   |   |
|  near, or into, the site of occlusion. Efficacy was attained  |   | |   |
| |                                                                   |   |
|  with greatly decreased dosage levels; mortality and          |   | |   |
| |                                                                   |   |
|  morbidity were decreased. The EKOS Peripheral Infusion       |   | |   |
| |                                                                   |   |
|  System is intended for controlled and selective infusion of  |   | |   |
| |                                                                   |   |
|  physician-specified fluids into the peripheral vasculature.  |   | |   |
| |                                                                   |   |
|  Infusion of thrombolytic agents is included in the intended  |   | |   |
| |                                                                   |   |
|  use of the EKOS infusion system. Potential benefits specific |   | |   |
| |                                                                   |   |
|  to the infusion of thrombolytics with this system may        |   | |   |
| |                                                                   |   |
|  include a decreased thrombolysis time (e.g., decreased time  |   | |   |
| |                                                                   |   |
|  from the start of the procedure to recanalization) due to    |   | |   |
| |                                                                   |   |
|  the improved dispersion and availability of the thrombolytic |   | |   |
| |                                                                   |   |
|  within the clot. This in turn may reduce the amount of       |   | |   |
| |                                                                   |   |
|  thrombolytic agent used. This result in reduced patient      |   | |   |
| |                                                                   |   |
|  discomfort, reduced risk of hemorrhage as a potential side   |   | |   |
| |                                                                   |   |
|  effect of thrombolytics and better patient health, and cost  |   | |   |
| |                                                                   |   |
|  savings to health care providers. The diagnostic flow sensor |   | |   |
| |                                                                   |   |
|  feature of EKOS Infusion systems could provide doctors with  |   | |   |
| |                                                                   |   |
|  real-time insight into the recanalization status of the      |   | |   |
| |                                                                   |   |
|  occluded lesion and could be used as an indicator for the    |   | |   |
| |                                                                   |   |
|  end of treatment.                                            |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Benefit to Company:**\                                     |   | |   |
| |                                                                   |   |
|  NIH SBIR/STTR funding provided development of critical       |   | |   |
| |                                                                   |   |
|  testing and contributed to the development and               |   | |   |
| |                                                                   |   |
|  commercialization of devices which we believe will improve   |   | |   |
| |                                                                   |   |
|  the health of 150,000 American patients with Peripheral      |   | |   |
| |                                                                   |   |
|  arterial occlusions and up to 500,000 patients who suffer    |   | |   |
| |                                                                   |   |
|  from ischemic strokes each year.                             |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **How Product Was Commercialized:**\                         |   | |   |
| |                                                                   |   |
|  While currently cleared by the FDA for sale in the US, EKOS  |   | |   |
| |                                                                   |   |
|  is electing to introduce these products in a controlled      |   | |   |
| |                                                                   |   |
|  release while collecting user feedback and experience. Full  |   | |   |
| |                                                                   |   |
|  market release for the peripheral products is expected in    |   | |   |
| |                                                                   |   |
|  Q4-05 and for the microcatheter in Q1-06.                    |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
| |                                                                   |   |
|  **Other Comments Related to Company\'s Success Story:**\     |   | |   |
| |                                                                   |   |
|  At a time when many U.S. manufacturing jobs have been        |   | |   |
| |                                                                   |   |
|  outsourced overseas, worldwide sales of EKOS infusion        |   | |   |
| |                                                                   |   |
|  systems will create manufacturing jobs in Northwest of the   |   | |   |
| |                                                                   |   |
|  USA.                                                         |   | |   |
| +                                                                   |   |
| --------------------------------------------------------------+---+ |   |
+---------------------------------------------------------------------+---+

+---------------------------------------------------------------------+---+
| **Transonic Systems** (Information Posted/Updated on 01/05/2006)\   |   |
| 34 Dutch Mill Road\                                                 |   |
| Ithaca, NY  14850\                                                  |   |
| \                                                                   |   |
| **Contact:**    Cornelis Drost\                                     |   |
| **Phone:**      607-257-5300\                                       |   |
| **Fax:**          607-257-7256\                                     |   |
| **E-mail:**      <cor.drost@transonic.com>\                         |   |
| **Web                                                               |   |
| Site:**  [http://www.transonic.com](http://www.transonic.com/)      |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  Tools and Techniques to Measure Flow and        |   |
| Pressure in Mice                                                    |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  1 R41 HL55082, 5 R44 HL55082-03              |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| SBIR Phase I & II funding enabled Transonic Systems, Inc. to        |   |
| develop, validate, and commercialize a new blood flow measurement   |   |
| meter and miniaturized flow sensors for transgenic mice studies.    |   |
| This technology is essential to studying cardiovascular diseases    |   |
| and their genetic causes and treatments.                            |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  Blood, Transit-Time, Mouse, Nanoprobes, Flow,       |   |
| Ultrasound, Implantable, Transgenic.                                |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| Transgenic mice are important disease study models because of the   |   |
| ready availability of animals genetically disposed to various       |   |
| diseases, and organ blood flow measurements are critical parts of   |   |
| these studies. For example, heart disease studies require cardiac   |   |
| output measurements, while hypertension studies require knowledge   |   |
| of kidney blood flow.                                               |   |
|                                                                     |   |
| Transgenic mouse studies promise to revolutionize medical           |   |
| treatment, and flow measurement tools are necessary to facilitate   |   |
| such innovations.                                                   |   |
|                                                                     |   |
| However, the arteries feeding mouse organs are extremely small --   |   |
| for example, the mouse kidney artery is only 0.3mm in diameter.     |   |
| Prior to this SBIR research, existing blood flow monitoring tools   |   |
| were too bulky for mice.                                            |   |
|                                                                     |   |
| Working with university collaborators at the Wake Forest School of  |   |
| Medicine and the Cornell National Nanofabrication Facility, we: \*  |   |
| Designed, fabricated and validated the smallest blood flow sensors  |   |
| ever built. \* Designed high-frequency electronics to operate these |   |
| sensors. \* Co-developed surgical protocols for implantation of     |   |
| sensors under PHS Policies and Guidelines. The new Transonic        |   |
| hardware will allow Transgenic mouse studies to proceed faster and  |   |
| with fewer animals, since the investigator can now monitor organ    |   |
| blood flow in conscious mice during the full course of a            |   |
| disease/treatment study.                                            |   |
|                                                                     |   |
| For product information and pictures of the commercialized          |   |
| hardware, see the following URL:                                    |   |
|                                                                     |   |
| <http://www.transonic.com/Research_Home/Products__Laborato          |   |
| ry_Research/420-Perivascular_Module/Mouse_Probes/mouse_probes.html> |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| SBIR Phase I & II funding enabled Transonic Systems, Inc. to        |   |
| develop, validate, and commercialize a new blood flow measurement   |   |
| meter and miniaturized flow sensors for transgenic mice studies.    |   |
| This technology is essential to medical studies of diseases and     |   |
| their genetic causes and treatments.                                |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| The product was promptly commercialized with Transonic internal     |   |
| funds -- the new probes and meter were shipped to worldwide         |   |
| customers by May 2002, one year after grant completion.             |   |
|                                                                     |   |
| Probe and electronics are manufactured at company headquarters in   |   |
| Ithaca, NY. Domestic sales and marketing are handled by             |   |
| Transonic-Ithaca, and international sales are handled through a     |   |
| worldwide network of Transonic sales representatives.               |   |
+---------------------------------------------------------------------+---+
| **Other Comments Related to Company\'s Success Story:**\            |   |
| At a time when many U.S. manufacturing jobs have been outsourced    |   |
| overseas, worldwide sales of Transonic sensors and meters have      |   |
| created new manufacturing jobs in rural Upstate New York.           |   |
+---------------------------------------------------------------------+---+

+---------------------------------------------------------------------+---+
| **ARISIL, Inc.** (Information Posted/Updated on 06/26/2006)\        |   |
| 450 Clinton Street\                                                 |   |
| Brooklyn, NY  11231\                                                |   |
| \                                                                   |   |
| **Contact:**    Dr. Shlomo Silman and Dr. Daniel S. Arick\          |   |
| **Phone:**      (718) 624-0222, (718) 951-4869\                     |   |
| **Fax:**          (718) 624-7310, (718) 951-4363\                   |   |
| **E-mail:**      <ssilman@brooklyn.cuny.edu>\                       |   |
| **Web                                                               |   |
| Site:**  [http://www.earpopper.com](http://www.earpopper.com/)      |   |
+---------------------------------------------------------------------+---+
| **Project Title:**  Non-Surgical Device for Treatment of Middle Ear |   |
| Effusion                                                            |   |
+---------------------------------------------------------------------+---+
| **Related Award(s):**  1R43DC003613-01A1, R44DC003613-03            |   |
+---------------------------------------------------------------------+---+
| **Technology Developed:**\                                          |   |
| Drs. Daniel S. Arick and Shlomo Silman of ARISIL, Inc. developed    |   |
| and patented (Patent \# US 5,419,672 and 5,885,242) the EarPopper,  |   |
| which has FDA 510(k) approval for marketing as a prescriptive       |   |
| medical device. The EarPopper is a hand-held, battery-operated      |   |
| modified Politzer autoinsufflation device that emits controlled air |   |
| pressure and flow that can be adjusted according to the patient\'s  |   |
| age and magnitude of hearing loss. It is used for non-surgical and  |   |
| non-pharmaceutical treatment of otitis media with effusion with     |   |
| associated hearing loss and Eustachian-tube dysfunction.            |   |
+---------------------------------------------------------------------+---+
| **Key Words:**  EarPopper, otitis media, middle-ear effusion,       |   |
| eustachian tube, autoinsufflation, Politzer method, manufacturing.  |   |
+---------------------------------------------------------------------+---+
| **Uses of Technology/Products/Service:**\                           |   |
| Middle ear fluid is one of the most common reasons that U.S.        |   |
| children visit the doctor, second only to the common cold,          |   |
| resulting in more than 30 million doctor visits each year and       |   |
| adding \$4 billion in medical costs to the health care system.      |   |
| Although increasing concerns about the risks of resistance to       |   |
| antibiotics recently led doctors to recommend \"watchful waiting\"  |   |
| as the first line of treatment, more than 10 million antibiotic     |   |
| prescriptions are written annually to treat middle ear fluid or     |   |
| otitis media with effusion (OME). Persistent OME often is treated   |   |
| with ear surgery. More than 700,000 children undergo this procedure |   |
| each year. In many cases, both antibiotics and surgery have proven  |   |
| problematic and often unsuccessful.                                 |   |
|                                                                     |   |
| The Ear Popper directs a steady, controlled stream of air into the  |   |
| nose, and swallowing diverts the air into the Eustachian tube,      |   |
| opening the Eustachian tube and relieving pressure imbalance in the |   |
| middle ear. The EarPopper can be used in the physician's office or  |   |
| parents can use the EarPopper at home on their children for a       |   |
| period of approximately 7 weeks. The results of the feasibility     |   |
| study and clinical trials conducted by ARISIL, Inc. revealed that   |   |
| the EarPopper was easy to use and well tolerated by children (4 or  |   |
| more years of age) as well as adults. The results also revealed     |   |
| that treatment with the EarPopper brought 73.9% of the treated ears |   |
| were within normal limits as compared with only 26.7% of the        |   |
| control ears that did not receive the EarPopper. When the treatment |   |
| period was extended for those who did not recover within 7 weeks,   |   |
| the recovery rate for the EarPopper increased to 84%. In these      |   |
| children, use of the EarPopper meant that they did not have to      |   |
| undergo ear surgery and they did not suffer the possible sequelae   |   |
| of ear surgery such as permanent hearing loss or permanent damage   |   |
| to the middle ear.                                                  |   |
+---------------------------------------------------------------------+---+
| **Benefit to Company:**\                                            |   |
| ARISIL, Inc. was privileged to receive two grants totaling          |   |
| \$1,024,123 from the National Institutes of Health (NIH) National   |   |
| Institute on Deafness and Other Communication Disorders (NIDCD) via |   |
| the Small Business Innovation Research (SBIR) Program. With this    |   |
| NIH NIDCD funding, ARISIL was able to construct the prototype       |   |
| EarPopper and to conduct the feasibility study and clinical trials  |   |
| with the device at Brooklyn College, CUNY, which kindly, under the  |   |
| aegis of President Christoph M. Kimmich, also provided ARISIL, Inc. |   |
| with support. ARISIL also benefited from the advice and             |   |
| consultation provided by Lynn E. Luethke, Ph.D., Program Director,  |   |
| Hearing Program, NIDCD/NIH. The feasibility and clinical trials     |   |
| results were extremely successful and two articles based on the     |   |
| clinical trials were published in Ear, Nose & Throat Journal in     |   |
| 2005.                                                               |   |
+---------------------------------------------------------------------+---+
| **How Product Was Commercialized:**\                                |   |
| In early 2005, ARISIL, Inc. enabled the technology for the intended |   |
| application to be commercialized when it leased the EarPopper to    |   |
| Micromedics, Inc., an innovative surgical products company located  |   |
| in St. Paul, MN. Micromedics, Inc. was one of several companies to  |   |
| approach ARISIL, Inc. for a leasing agreement for the EarPopper.    |   |
| Micromedics, Inc. had conducted its own successful feasibility      |   |
| study on the EarPopper before the leasing agreement between ARISIL, |   |
| Inc., and Micromedics, Inc. was finalized. Micromedics, Inc. made   |   |
| the EarPopper commercially available beginning October, 2005. The   |   |
| company widely promotes the EarPopper in the U.S. and abroad. The   |   |
| website for Micromedics, Inc. is                                    |   |
| [http://www.micromedics-usa.com](http://www.micromedics-usa.com/)   |   |
| and it maintains a site for the EarPopper at                        |   |
| [http://www.earpopper.com](http://www.earpopper.com/).              |   |
+---------------------------------------------------------------------+---+
| **Other Comments Related to Company\'s Success Story:**\            |   |
| The EarPopper received media coverage through more than 45          |   |
| health/medical reports on television stations, radio, newspapers,   |   |
| and professional health journals throughout the country and on      |   |
| health/medical websites. Examples of media coverage include         |   |
| Washingon Post, Wall Street Journal, ABC, CBS and NBC, National     |   |
| Public Radio, the New York Daily News. It also has appeared on      |   |
| several health websites. Numerous letters of appreciation from      |   |
| parents and physicians were sent to Drs. Arick and Silman and some  |   |
| also appear on the EarPopper website.                               |   |
+---------------------------------------------------------------------+---+

2.  Procedures and mechanisms NIH has used to date to give priority to
    manufacturing-related projects.

NIH SBIR announcements encourage development of new technologies as well
as application of existing technologies.  When appropriate, plans for
manufacturing and clinical evaluation of developed technologies, drugs,
devices and innovative approaches should be included in the
application. 

3.  Actions your agency has taken toward promoting and supporting
    manufacturing-related research projects.

The NIH focused on the following procedures and mechanisms to give
priority to manufacturing-related SBIR/STTR projects: a) Outreach to
raise awareness; b) Announcements for funding opportunities and c) Award
selection.

a)  **Outreach to raise awareness of E.O. 13329 to the small business
    research community** - Ongoing as part of presentations to small
    business applicants across the United States.

> **b) Announcement of funding opportunities for manufacturing-related
> research**
>
> **[*NIH Guide for Grants and Contracts*.]{.underline}** Developed and
> promoted, through a trans-DHHS Program Announcement (PA), PA-04-161
>
> MANUFACTURING PROCESSES OF MEDICAL, DENTAL, AND BIOLOGICAL
> TECHNOLOGIES (SBIR/STTR) broad topic areas for NIH, CDC and FDA that
> are considered relevant to manufacturing-related R&D. In FY 2005, NIH
> received 35 applications and issued 4 awards in response to this
> program announcement.
>
> The PA was reissued in October 2005, increasing the IC participation
> from 19 components to 29 participating DHHS components for the SBIR
> program and released a separate PA for STTR. for 19 components. The
> current broad topic PAs will remain open for three years and will
> utilize the standard submission dates: April 1, August 1 and December
> 1 of each calendar year.
>
> Program Announcement NUMBER: PA-06-013 and PA-06-012
>
> <http://grants2.nih.gov/grants/guide/pa-files/PA-06-013.html>
>
> <http://grants2.nih.gov/grants/guide/pa-files/PA-06-012.html>
>
> **Department of Health and Human Services**
>
> **Participating Organizations**\
> National Institutes of Health (NIH)\
> Centers for Disease Control and Prevention (CDC)\
> Food and Drug Administration (FDA)
>
> **Components of Participating Organizations**\
> National Institute on Aging (NIA)\
> National Institute on Alcohol Abuse and Alcoholism (NIAAA)\
> National Institute of Allergy and Infectious Diseases (NIAID)\
> National Institute of Biomedical Imaging and Bioengineering (NIBIB)\
> National Cancer Institute (NCI)\
> National Institute on Deafness and Other Communication Disorders
> (NIDCD)\
> National Institute of Dental and Craniofacial Research (NIDCR)\
> National Institute of Diabetes and Digestive and Kidney Diseases
> (NIDDK)\
> National Institute on Drug Abuse (NIDA)\
> National Institute of Environmental Health Sciences (NIEHS)\
> National Eye Institute (NEI)\
> National Institute of General Medical Sciences (NIGMS)\
> National Heart, Lung, and Blood Institute (NHLBI)\
> National Institute of Mental Health (NIMH)\
> National Institute of Neurological Disorders and Stroke (NINDS)
>
> National Institute of Nursing Research (NINR)\
> National Center for Research Resources (NCRR )
>
> National Center for Complementary and Alternative Medicine (NCCAM)\
> National Library of Medicine (NLM)\
> National Institute for Occupational Safety and Health (NIOSH/CDC)\
> National Center on Birth Defects and Developmental Disabilities
> (NCBDDD/CDC),  \
> National Center for Chronic Disease Prevention and Health Promotion
> (NCCDPHP/CDC),\
> National Center for Environmental Health (NCEH/CDC)\
> National Center for Injury Prevention and Control (NCIPC/CDC)\
> Center for Biologics Evaluation and Research (CBER/FDA)\
> Center for Drug Evaluation and Research (CDER/FDA) \
> Center for Food Safety and Applied Nutrition (CFSAN/FDA),\
> Center for Veterinary Medicine (CVM/FDA)\
> Office of Orphan Products Development (OPD/FDA)
>
> ***[NIH Guide for Grants and Contracts]{.underline}*** Added the
> manufacturing component through a reissuance of trans-DHHS Program
> Announcement (PA),
> [PA-04-156](http://grants.nih.gov/grants/guide/pa-files/PA-04-156.html)
> in areas of high program priority for NIH.
>
> **Title:** Bioengineering Approaches to Energy Balance and Obesity.
>
> **Department of Health and Human Services**
>
> **Participating Organizations**\
> National Institutes of Health (NIH)\
> Co**mponents of Participating Organizations:\
> **National Heart, Lung, and Blood Institute (NHLBI),
> ([http://www.nhlbi.nih.gov](http://www.nhlbi.nih.gov/))\
> National Institute of Biomedical Imaging and Bioengineering (NIBIB),
> ([http://www.nibib.nih.gov](http://www.nibib.nih.gov/))\
> National Institute of Diabetes and Digestive and Kidney Diseases
> (NIDDK), ([http://www.niddk.nih.gov](http://www.niddk.nih.gov/))\
> National Cancer Institute (NCI),
> ([http://www.nci.nih.gov](http://www.nci.nih.gov/))\
> National Institute on Aging (NIA),
> ([http://www.nia.nih.gov](http://www.nia.nih.gov/))
>
> Two separate PAs were reissued in November, 2005: PA-06-055 for SBIR
> and PA-06-056 for STTR. NIH received five (5) applications in FY2005.
>
> **Two additional topic concepts with significant manufacturing
> components are pending council approval for FY 2006.**

**January 2005 [SBIR/STTR Program Solicitation.]{.underline}** Included
within an IC's topic listings, topic areas specific to
manufacturing-related areas in the PHS Omnibus Solicitation of the NIH,
CDC and FDA SBIR/STTR Grant Solicitation.

**July 2005** Discuss E.O. 13329 at the 7*th Annual NIH SBIR/STTR
Conference* to raise awareness of manufacturing issues in the U.S.

> Power Point Presentation by NIST MEP representative to provide
> information on the MEP to attendees at the 7*th Annual NIH SBIR/STTR
> Conference* as a resource to SBIR manufacturers.

**August 2005** Post link to NIST's Manufacturing Extension Partnership
(MEP) program website on the NIH SBIR/STTR Program webpage.

**Ongoing** **[Coordination with other Public Programs.]{.underline}**

> The NIH is working with the National Institute of Standards and
> Technology's (NIST) Manufacturing Extension Program (MEP) to develop a
> pilot program which will be the third item on a menu of NIH assistance
> initiatives intended to help move NIH SBIR awardees toward
> commercialization. The NIH/NIST MEP pilot program is intended to
> provide transitional support as companies move to a development stage
> that requires decisions in operational transition strategies.
> Decisions made early in the development process typically drive the
> costs of output and associated business management strategies
> throughout the business cycle. As a result of this pending pilot
> effort participating companies will be able to make better operational
> decisions converting their research into products by:

a)  Decreasing development costs and cycle time to market

b)  Minimizing anticipated operational expenses and increasing product
    quality, thus

c)  Raising the ROI on NIH SBIR funding to small companies

> Conducted at a pilot level, successful results from this stage may
> suggest an on-going effort in partnership between NIH and NIST
> Manufacturing Extension Program (MEP). In 2005, 23 NIH Phase II
> companies participated with the NIST MEP for activities such as ISO
> 9000, manufacturing plant layout and process flow, strategic planning
> for LEAN, interim business and financial management, feasibility
> studies, prototyping of sensors, LEAD training and prototype
> manufacturing, value stream mapping, and STL programming
> turbomachining. These interactions between MEP and NIH companies lead
> us to believe that the proposed NIH/NIST MEP pilot is appropriate for
> a wide variety of NIH Phase II SBIR research projects, including
> clinical projects (both drug and device development), IT, software,
> multimedia and education projects, as well as those in the behavioral
> sciences.

**Ongoing** - Promoting the manufacturing initiative through
conferences, meetings, and website notices.

**Ongoing -** Tracking and reporting success stories on the NIH SBIR
website that show the impact of the SBIR/STTR programs on manufacturing.
See [***SBIR and STTR Success
Stories***](http://grants1.nih.gov/grants/funding/sbir_successes/sbir_successes.htm)