UTA_UTSW_GERD_071228

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					BESTTM for GERD

Batteryless Endoluminal Sensing Telemeter
for
GastroEsophageal Reflux Disease

Dr. Shou Jiang Tang, Department of Medicine, UTSW
Dr. Stuart Spechler, Department of Medicine, UTSW
Dr. Fred Tibbals, Bioinstrumentation, UTSW
Dr. J.C. Chiao, Electrical Engineering, UT-Arlington




            Prof. J.C. Chiao  www.uta.edu/faculty/jcchiao  jcchiao@uta.edu   i MEMS
Gastroesophageal Reflux Disease (GERD)

                                         Acid reflux caused from lower
                                         esophageal sphincter (LES)
                                         open at a wrong time.
  LES

                                         GERD symptoms
                                         - Heartburn
                                         - Esophageal cancer
                                         - Acid reflux
                                         - Nonacid reflux

                          www.GERD.com   19 million people in USA
                                         may have GERD

Confidential and Proprietary                           jcchiao@uta.edu   i MEMS
 Diagnosing GERD with catheter-based
 impedance probe




         Very uncomfortable and embarrassing
Confidential and Proprietary                   jcchiao@uta.edu   i MEMS
BESTTM: Passive Wireless Impedance Sensor




                                                   Implant
                                                               Esophagus



  A photo of the implant
                                                                    Acid
  on a flexible substrate.
                                 Data
                                 log
                                 screen

                                                               Stomach
                                              Memory stick
                               External receiver



   Patient friendly
Confidential and Proprietary                                 jcchiao@uta.edu   i MEMS
          TM
BEST           distinguishes air, water and acid.


                   Air           Water              Acid




 Impedance monitoring distinguishes air, water and
 acid, and is able to detect both acid and nonacid
 episodes.


Confidential and Proprietary                  jcchiao@uta.edu   i MEMS
 Real-time measurement results: video




Confidential and Proprietary            jcchiao@uta.edu   i MEMS
 BESTTM for GERD sensor size

 Our prototype footprint is comparable with commercial
 product BRAVO but thinner. The end product will be smaller.




Confidential and Proprietary                          jcchiao@uta.edu   i MEMS
BESTTM for GERD, In vivo experiments
 • Porcine models: 3 female pigs, each 75 lbs. with chest
   perimeter=70cm.
 • Implant location: 3cm above GE-junction
 • A nasogastric (NG) tube in the esophagus for flushing
   various solutions
 • Endoscope to monitor implant and fluidic activities
 • Surgical suction tube in the endoscope accessory
   channel to remove excessive gastric fluid




Confidential and Proprietary                                jcchiao@uta.edu   i MEMS
 Impedance sensor can detect nonacid
 reflux

                         12                                       10.5




                                                                         Impedance reading
     pH sensor reading




                         11               BRAVO                   10.3

                         10                                       10.1

                         9                                        9.9

                         8                                        9.7
                                                    BESTTM
                                                         for GERD
                         7                                        9.5
                              7   8   9        10     11       12
                                          pH

  BRAVO malfunctions for pHs above 10.7.
  Impedance sensing detects all episodes.


Confidential and Proprietary                                       jcchiao@uta.edu           i MEMS
                                                                                                           Impedance Sensor, Freuqnecy Shift, kHz




                                                                            -2.5
                                                                                                    -1.5
                                                                                                                              -0.5
                                                                                                                                                     0.5
                                                                                                                                                                         1.5
                                                                                                                                                                                                                                                                 2.5




                                                                                         -2
                                                                                                                -1
                                                                                                                                         0
                                                                                                                                                                   1
                                                                                                                                                                                               2
                                                                                                   Water
                                                                                                      Water
                                                                                                           Water
                                                                                                             Water
                                                                                     Diet coke
                                                                                                             Diet coke
                                                                                                Diet coke
                                                                                                     Diet coke
                                                                                   Diet coke
                                                                                                             Water
                                                                                                                       Diet coke
                                                                                    Diet coke
                                                                                                       Water
                                                                                                Regular coke
                                                                                                          Regular coke
                                                                                                     Regular coke
                                                                                                          Regular coke
                                                                                        Regular coke
                                                                                       Regular coke
                                                                                                   Water




 Confidential and Proprietary
                                                                                                         Regular coke
                                                                                     Regular coke
                                                                                               Water
                                                                                                   Water
                                                                                                                  OJ N/P
                                                                                                                                               OJ N/P
                                                                                                                                                OJ N/P
                                                                                                                                                  OJ N/P
                                                                                                                                                      OJ N/P
                                                                                                                                                      OJ N/P
                                                                                                                                                Water
                                                                                                                 Water
                                                                                                                    Water
                                                                                                    Water
                                                                                                                                                OJ W/P
                                                                                                                                                   OJ W/P
                                                                                                                                                   OJ W/P
                                                                                                                                                    OJ W/P
                                                                                                                       Water
                                                                                                              Water
                                                                                                            Vinegar
                                                                                                                                                  Vinegar
                                                                                                                                                  Vinegar
                                                                                                                                                  Vinegar
                                                                                                                Water
                                                                                                             Water
                                                                                                             Water
                                                                                                                                                             Acid
                                                                                                                                                                      Acid
                                                                                                                                                                 Acid
                                                                                                                                                                     Acid
                                                                                                                                                                      Acid
                                                                                                                                                                         Water
                                                                                                                                                                             Water
                                                                                                                                                             Water
                                                                                                                      Water
                                                                                                                                                           Water
                                                                                                                  Water
                                                                                                                       Water
                                                                                                               Water
                                BRAVO malfunctions for alkaline solutions                                     Water
                                                                                                                        Water
                                                                                                                                                            Water
                                                                                                                                                                Water
                                                                                                                                                           Water
                                                                                                                  Water
                                                                                                                                                                                    Impedance sensing detects every episodes of water reflux.




                                                                                                                 Water
                                                                                                                                                                                                                                                                       Impedance Sensor vs pH Sensor with Episodes




                                                                                         Dry
                                                                                                           Alkaline
                                                                                                            Alkaline
                                                                                                                         Alkaline
                                                                                                                                                     Alkaline
                                                                                                                                             Alkaline
                                                                                                                          Water
                                                                                                                       Water
                                                                                                                    Water
                                                                                                                 Water
                                                                                                               Water
                                                                                                             Water
 jcchiao@uta.edu




                                                                                                             Water
                                                                                                                                                                                    BRAVO values stay flat due to the inability to distinguish water from air.




                                                                                                           Water
                                                                                                           Water
                                                                            0
                                                                                     1
                                                                                               2
                                                                                                      3
                                                                                                               4
                                                                                                                        5
                                                                                                                                     6
                                                                                                                                         7
                                                                                                                                                 8
                                                                                                                                                           9
                                                                                                                                                                    10
                                                                                                                                                                         11
                                                                                                                                                                               12
                                                                                                                                                                                                                     13
                                                                                                                                                                                                                                                                 14




i MEMS




                                                                                                                                 pH sensor, pH
 BESTTM for GERD
  Features
         • Impedance sensing
            • More accurate than pH sensing
            • Identify non-acid (neutral/alkaline) reflux

         • Passive wireless telemetry
            • No battery needed
            • Long term measurement

         • Flexible packaging
            • Biocompatible
            • Safe
Confidential and Proprietary                  jcchiao@uta.edu   i MEMS
 BESTTM for GERD

• Presented at Digestive Disease Week, 2007
• Paper submitted to DDW’08, IEEE Trans. of Biomed. Eng.
• Media coverage: 57
  • Voice of America, TV and Webcast
  • AM820 WBAP, June 2 2007
  • NBC DFW Channel-5 Evening News, June 5 2007
  • NBC Lubbock Channel-11 Evening News, June 8 2007
  • RFID Journal, March 2007
  • Medical Device & Diagnostic Industry Magazine, Aug.
    2007
  • Reported by the New York Society for Gastrointestinal
    Endoscopy (NYSGE).


Confidential and Proprietary                  jcchiao@uta.edu   i MEMS
  Market Size –
      LeadDiscovery:
      The World Gastrointestinal Disorders Market 2006-2011
         Gastrointestinal (GI) disorders market is one of the largest in
         the pharmaceutical industry, generating revenues of over $16B
         in 2004.

      GERD is one of the most common conditions in the US, with 44% of
      adults suffering at least one episode per month.

      For patients with serious GERD and received further diagnosis,
      95% are using tethered pH sensors.

      Global market: 15% adult population may have GERD. Screening
      need is tremendous.

      Our devices are appropriate for children diagnosis – new markets

Confidential and Proprietary                           jcchiao@uta.edu   i MEMS
   Market Size –
Chip demands (conservative estimate):

• Each sensor will have at least one TI chip and several other chips
• Wearable reader (potentially disposable) will have at least 4 TI chips
  (including power-efficient DSPs/MCU) and one antenna

• 10% potential GERD patients in US need screening: 9.5 millions of DSP
  chips needed


Applications of TI chips in our sensor systems
  • Ultra-low power MSP430 microcontrollers (MCU)
  • Power-efficient TMS320VC54xdigital signal processors (DSP)
  • TRF7960 family of reader ICs
  • Reader antenna such as RI-ANT-P02A
  • Future development of RFICs such as RI-UHF-00001-01 and RF-
  HDT-WNME chips

Confidential and Proprietary                            jcchiao@uta.edu   i MEMS
 Commercial competition

 Expert advocate: Drs. Stuart Spechler and Shou-Jiang Tang are world
 famous clinicians and expert on GERD.

  Newsweek: Sept. 11 2005 Issue


                                   Chinese Medicine Info: 2007 Issue




Confidential and Proprietary                             jcchiao@uta.edu   i MEMS
 Commercial competition

 Medtronics
    Only Bravo devices are commercially available.
    Bravo devices are used now but not widely.
    Bravo only measures pH and only detects acid reflux.
    Issues: size, accuracy, comfort levels, one sensor only.


Commercialization progress

  3 medical device companies have contacted us and signed NDAs.

  A VC company has contacted us to start a new business.




Confidential and Proprietary                           jcchiao@uta.edu   i MEMS
Peer reviews in literatures about pH and impedance sensing methods

           Original papers attached in pdf format




Confidential and Proprietary                        jcchiao@uta.edu   i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

pH sensor does not detect nonacid episodes
“Physical and pH Properties of Gastroesophagopharyngeal Refluxate: A 24-hour Simultaneous
Ambulatory Impedance and pH Monitoring Study,” Osamu Kawamura, M.D., Muhammad Aslam,
M.D., Tanya Rittmann, Candy Hofmann, R.N., and Reza Shaker, M.D., The American Journal of
Gastroenterology, Volume 99, Issue 6, Page 1000-1010, June 2004.
File: 1_Comparison_of_pH_and_impedance_clinical_trial.pdf

Concurrent impedance and pH recordings detect significantly more events
qualifying as reflux in the pharynx than pH recordings alone. A substantial
majority of these events are gaseous refluxes both with and without minor pH
drops. Gas reflux events with weak acidity appear to be more common among
patients with reflux-attributed laryngeal lesions compared to GERD patients and
controls.

When comparing impedance and pH findings, impedance recording detected
significantly more events than pH recording. An overwhelming majority of these
events were without pH changes and were gaseous reflux. A significant minority of
about 20% of gas reflux events were accompanied by monor pH drops that
ordinarily are discounted when found on pH recording alone.

Confidential and Proprietary                                        jcchiao@uta.edu   i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

 pH sensor does not detect nonacid episodes
 Impedance monitoring is more accurate for detection of
 both acid and non-acid reflux, but its clinical utility has
 yet to be realized.
“Modern technology in the diagnosis of gastro-oesophageal reflux disease : Bilitec, intraluminal
impedance and Bravo capsule pH monitoring,” Hirano, I., Alimentary pharmacology & therapeutics,
2006, vol. 23, no 1, pp. 12-24. File: 2_Modern technology in the diagnosis of GERD.pdf
 …. pH testing has several limitations, including issues of sensitivity, specificity,
tolerability and the inability to record non-acid reflux events.
 …. When combined with pH monitoring, impedance monitoring enhances the
detection and characterization of gastro-oesophageal reflux and may have a role in
the evaluation of certain specific gastro-oesophageal reflux disease (GERD)
symptoms that persist despite acid suppression therapy.
  Recent investigations reporting clinical significance to DGER in patients failing PPI
therapy need to be validated using better statistical assessment of symptom
association. Impedance monitoring has been demonstrated to be an accurate
diagnostic technique for detection of both acid and non-acid reflux, but its clinical
utility has yet to be realized.

Confidential and Proprietary                                            jcchiao@uta.edu   i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

Impedance detection is more sensitive than pH detection
“Esophageal Impedance Monitoring: The Ups and Downs of a New Test,” Steven Shay, M.D.,
F.A.C.P., The American Journal of Gastroenterology, Volume 99 Issue 6 Page 1020-1022, June
2004.
File: 3_Impedances_postives and negatives.pdf

 Impedance monitoring has been validated in acid reflux detection by identifying
 97–98% of acid reflux detected by the pH probe in normal subjects and GERD
 patients. More importantly, it also detected 93% of nonacid and superimposed
 acid reflux detected by common cavity and not by pH probe.




Confidential and Proprietary                                           jcchiao@uta.edu       i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

Impedance detection is the new gold standard

“Will esophageal impedance replace pH monitoring?. [Review],” Y. Salvatore, S. MC. Vieira, B.
    Hauser, Pediatrics. 2007;119(1):118-22.
File: 4_Pediatrics 2007-eso impedance-review.pdf


 Because pH monitoring is part of impedance technology, it is predicted that
 impedance testing will soon replace pH monitoring despite the current need of
 scientific evidence demonstrating a relation between symptoms, esophageal
 damage or response to reflux treatment …

 Impedance allows the detection of the frequency, the height (in the esophagus),
 and duration of reflux episodes independent of the pH of the refluxate.
 Experience with pH monitoring has shown the pitfalls of an arbitrary pH cutoff
 limit such as 4.0.




Confidential and Proprietary                                             jcchiao@uta.edu   i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

Impedance detection is the new gold standard

“Combined Multichannel Intraluminal Impedance and pH-Metry: An Evolving Technique to
    Measure Type and Proximal Extent of Gastroesophageal Reflux,” Donald O. Castell, MD,
    Marcelo Vela, MD, The American Journal Of Medicine, 111 (8A), 157-179S, December 3,
    2001
File: 5_Am J Med 01-review-eso impedance.pdf


 The accepted “gold standard” for measuring gastroesophageal reflux (GER),
 distal esophageal pH recording, has limited ability to measure nonacid GER, a
 potentially important cause of symptoms, in an era of potent acid-suppressing
 medications. A combination of multichannel intraluminal impedance (MII) and
 pHmetry offers an advantage over pH measurement alone. MII can detect GER at
 multiple levels of the esophagus independent of pH. In addition, use of MII
 enables refined characterization of intraluminal events, including presence, type
 (air, liquid, or mixed), and spaciotemporal characterization of a bolus. MII has the
 potential to become a useful clinical tool to assess ongoing reflux in patients on
 acid-suppression therapy.


Confidential and Proprietary                                          jcchiao@uta.edu      i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

Wireless pH monitor is recommended for 4 days.
Battery-based wireless device has limited life.
Impedance detection is superior to pH monitoring
“ACG Practice Guidelines: Esophageal Reflux Testing,” Ikuo Hirano, M.D.,1 Joel E.
    Richter, M.D.,2 and the Practice Parameters Committee of the American College of
    Gastroenterology, American Journal of Gastroenterology, 2007;102:668–685).
File: 6_Am J Gastro 2007-eso testing in GERD-guidelines.pdf

 The use of the wireless pH system for 4-day recordings allows for combined
 testing both off and on PPI therapy and may circumvent certain limitations of on-
 therapy testing (19). While both bile acid reflux monitoring and esophageal
 impedance are very promising technologies, further studies are needed to
 determine their role in patients with refractory reflux. Impedance is superior to pH
 monitoring in the detection of reflux symptoms associated with weakly acidic or
 nonacid reflux that persists on PPI therapy, especially regurgitation.



Confidential and Proprietary                                      jcchiao@uta.edu   i MEMS
BESTTM for GERD vs Bravo wireless pH sensor

Wireless pH monitor is recommended for more than 4
days but currently the BRAVO batteries only last for 2
days unless specially prolonged.

 BESTTM is batteryless so measurement time is unlimited

“The Impact of Prolonged pH Measurements on the Diagnosis of Gastroesophageal
    Reflux Disease: 4-Day Wireless pH Studies,” Giuseppe Scarpulla, M.D., Salvatore
    Camilleri, M.D., Pietro Galante, M.D., Miohele Manganaro, M.D.,and Mark Fox, M.D.,
    American Journal of Gastroenterology, 1572-0241.2007.
File: 7_Am J Gastro 2007-prolonged pH testing is better-Bravo.pdf


 A diagnosis consistent with the 96-h “gold standard” was present in 22 (63%), 29
 (83%), and 32 (91%) patients for 24-, 48-, and 72-h test periods, respectively, with a
 significant improvement of diagnostic sensitivity with study duration (P < 0.01). ….
 Increasing the duration of pH studies progressively improves measurement
 variance and the diagnostic reproducibility of reflux studies.

Confidential and Proprietary                                      jcchiao@uta.edu   i MEMS

				
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