intraperitoneal glucose sensing’–r apid and 2015 poster - an… · intraperitoneal glucose...

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RESULTS Summary 3 trials, 4–7 segments from each trial. Time delays: 0–15 seconds (median: 9.0 s, mean: 6.74 s, stdev: 6.76 s). Time constants: 1–15 min (median: 4.20 min, mean: 5.03 min, stdev: 4.05 min). Examples from 6 segments: Time Response Comparison Time (minutes) Amplitude 2 4 6 8 10 12 14 16 18 6.5 7 7.5 8 8.5 9 9.5 10 10.5 11 11.5 Trial 1, zone A. Fit: 77.65 % Intraperitoneal glucose sensor Intraarterial sensor filtered through estimated transfer function Intraperitoneal sensor Time Response Comparison Time (minutes) Amplitude 5 10 15 20 25 30 35 5.5 6 6.5 7 7.5 8 8.5 9 Trial 1, zone B. Fit: 86.91 % Intraperitoneal glucose sensor Intraarterial sensor filtered through estimated transfer function Intraperitoneal sensor Es<mated linear transfer func<ons (from blood to peritoneum) Based on relaBonship between IA and IP sensor signals. H P = K 1 +2.2 s H P = K 1 +8.3 s Time [minutes] 0 5 10 15 20 25 30 35 40 Glucose concentration estimate [mmol/L] 5 6 7 8 9 10 11 12 13 14 Trial 1, zone C. T = 14.8 [min]. Delay: 0 [min]. Fit = 70.16 %. Intraarterial sensor Intraperitoneal sensor Glucose bolus Blood gas analysis Subcutaneous sensor Time [minutes] 0 5 10 15 20 25 30 Glucose concentration estimate [mmol/L] 5 6 7 8 9 10 11 12 13 14 Trial 1, zone D. T = 4.4 [min]. Delay: 0 [min]. Fit = 81.75 %. Intraarterial sensor Intraperitoneal sensor Glucose bolus Blood gas analysis Subcutaneous sensor Time [minutes] 0 5 10 15 Glucose concentration estimate [mmol/L] 4 5 6 7 8 9 10 Trial 3, zone F. T = 1.2 [min]. Delay: 0.21 [min]. Fit = 73.86 %. Intraarterial sensor Intraperitoneal sensor Glucose bolus Blood gas analysis Subcutaneous sensor Time [minutes] 0 2 4 6 8 10 12 Glucose concentration estimate [mmol/L] 5 5.5 6 6.5 7 7.5 8 8.5 9 Trial 3, zone E. T = 1.1 [min]. Delay: 0.15 [min]. Fit = 59.21 %. Intraarterial sensor Intraperitoneal sensor Glucose bolus Blood gas analysis Subcutaneous sensor C A B A D B F E REFERENCES METHODS INTRAPERITONEAL GLUCOSE SENSING –RAPID AND ACCURATE Anders Fougner 1,2,6 , Konstanze Kölle 1,2,6 , Nils KrisBan Skjærvold 1,3,7 , NicolasAndreas Elvemo 8 , Reinold Ellingsen 1,4,8 , Sven Magnus Carlsen 1,5,7 , and Øyvind Stavdahl 1,2 [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] MOTIVATION Animal trials 3 anaestheBzed nondiabeBc pigs Intravenous infusion of glucose boluses Glucose level excursions within the range 5–22 mmol/L Sensor types used in trials Intraarterial (IA): OpBcal interferometric phenylboronic acid based sensors, placed in the femoral artery [3,4]. Intraperitoneal (IP): Using the same sensor as in the IA case. Accessed from below the umbilicus through a common port, directed to 4 different posiBons (Fig. on the right). 2–4 sensors per animal. Subcutaneous (SC): Offtheshelf amperometric enzymebased (glucose oxidase) sensors. Placed on the belly, above the umbilicus. Venous blood was sampled and analyzed on a blood gas analyzer (BGA) for reference and calibraBon of the other sensors. CONCLUSION Why intraperitoneal sensing? Subcutaneous glucose sensors: Slow response, poor robustness towards local Bssue effects (mechanical pressure, temperature etc). Intravascular glucose sensors: Not pracBcally possible outside of the hospital/clinic. We need a rapid, accurate and robust glucose measurement for making a safe arBficial pancreas. Intraperitoneal glucose sensors may react faster than subcutaneous sensors [1,2], while being more pracBcally usable than intravascular sensors. Norwegian University of Science and Technology (NTNU), Trondheim, Norway Intraperitoneal glucose sensors can have a substanBally faster and more disBncBve response than subcutaneous sensors. Our results indicate that IP sensors may react even faster than previously shown [2]. Variable dynamics during the experiments + some sensors had to be relocated > Need to invesBgate disturbances & sensor locaBon in more detail. [1] Velho, G., Froguel, P., and Reach, G., “DeterminaBon of peritoneal glucose kineBcs in rats: implicaBons for the peritoneal implantaBon of closedloop insulin delivery systems,” Diabetologia, vol. 32, no. 6, pp. 331–336, 1989. [2] Burneo, D. R., Huyeo, L. M., Zisser, H. C., Doyle III, F. J., and Mensh, B. D., ”Glucose Sensing in the Peritoneal Space Offers Faster KineBcs than Sensing in the Subcutaneous Space,” Diabetes, vol. 63, no. 7, pp. 2498–2505, July 2014. [3]Skjærvold, N. K., Solligård, E., Hjelme, D. R., and Aadahl, P., “ConBnuous measurement of blood glucose: validaBon of a new intravascular sensor,” Anesthesiology, vol. 114, no. 1, 120–125, 2011. [4]Skjærvold, N. K., Østling, D., Hjelme, D. R., Spigset, O., Lyng, O., and Aadahl, P., “Blood Glucose Control Using a Novel ConBnuous Blood Glucose Monitor and RepeBBve Intravenous Insulin Boluses: ExploiBng Natural Insulin PulsaBlity as a Principle for a Future ArBficial Pancreas,” Interna1onal Journal of Endocrinology, vol. 2013, ArBcle ID 245152, 2013. 6 Helse MidtNorge – The Central Norway Regional Health Authority, Norway 7 St Olavs University Hospital, Trondheim, Norway 8 GlucoSet AS, Trondheim, Norway 1 ArBficial Pancreas Trondheim – The APT research group (www.aptnorway.com ) 2 Department of Engineering CyberneBcs 3 Department of CirculaBon and Medical Imaging 4 Department of Electronics and TelecommunicaBons 5 Unit for Applied Clinical Research, Faculty of Medicine Hydrogel sensor Incident light Reflected light Readout instrument Interference OpBcal fiber Op<cal interferometric sensors Sensor placement 10 cm IP 10 cm 10 cm 10 cm SC IA sensor UL IP LR IP LL IP UR Glucose boluses & BGA

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Page 1: INTRAPERITONEAL GLUCOSE SENSING’–R APID AND 2015 Poster - An… · Intraperitoneal glucose sensor Intraarterialsensor filtered through estimated transfer function Intraperitoneal

RESULTS  

Summary  •  3  trials,  4–7  segments  from  each  trial.  

•  Time  delays:  0–15  seconds  (median:  9.0  s,  mean:  6.74  s,  stdev:  6.76  s).  

•  Time  constants:  1–15  min  (median:  4.20  min,  mean:    5.03  min,  stdev:  4.05  min).  

Examples  from  6  segments:  

Time Response Comparison

Time (minutes)

Ampl

itude

2 4 6 8 10 12 14 16 186.5

7

7.5

8

8.5

9

9.5

10

10.5

11

11.5Trial 1, zone A. Fit: 77.65 %

Intr

aper

itone

al g

luco

se s

enso

r

Intraarterial sensor filteredthrough estimated transfer functionIntraperitoneal sensor

Time Response Comparison

Time (minutes)

Ampl

itude

5 10 15 20 25 30 355.5

6

6.5

7

7.5

8

8.5

9Trial 1, zone B. Fit: 86.91 %

Intr

aper

itone

al g

luco

se s

enso

r

Intraarterial sensor filteredthrough estimated transfer functionIntraperitoneal sensor

Es<mated  linear  transfer  func<ons  (from  blood  to  peritoneum)  Based  on  relaBonship  between  IA  and  IP  sensor  signals.  

HP = K1+2.2s HP = K

1+8.3s

Time [minutes]0 5 10 15 20 25 30 35 40

Glu

cose

con

cent

ratio

n es

timat

e [m

mol

/L]

5

6

7

8

9

10

11

12

13

14Trial 1, zone C. T = 14.8 [min]. Delay: 0 [min]. Fit = 70.16 %.

Intraarterial sensorIntraperitoneal sensorGlucose bolusBlood gas analysisSubcutaneous sensor

Time [minutes]0 5 10 15 20 25 30

Glu

cose

con

cent

ratio

n es

timat

e [m

mol

/L]

5

6

7

8

9

10

11

12

13

14Trial 1, zone D. T = 4.4 [min]. Delay: 0 [min]. Fit = 81.75 %.

Intraarterial sensorIntraperitoneal sensorGlucose bolusBlood gas analysisSubcutaneous sensor

Time [minutes]0 5 10 15

Glu

cose

con

cent

ratio

n es

timat

e [m

mol

/L]

4

5

6

7

8

9

10Trial 3, zone F. T = 1.2 [min]. Delay: 0.21 [min]. Fit = 73.86 %.

Intraarterial sensorIntraperitoneal sensorGlucose bolusBlood gas analysisSubcutaneous sensor

Time [minutes]0 2 4 6 8 10 12

Glu

cose

con

cent

ratio

n es

timat

e [m

mol

/L]

5

5.5

6

6.5

7

7.5

8

8.5

9Trial 3, zone E. T = 1.1 [min]. Delay: 0.15 [min]. Fit = 59.21 %.

Intraarterial sensorIntraperitoneal sensorGlucose bolusBlood gas analysisSubcutaneous sensor

C  

A

BA

D

B

F  

E  

REFERENCES  

METHODS  

 INTRAPERITONEAL  GLUCOSE  SENSING  –  RAPID  AND  ACCURATE  

Anders  Fougner1,2,6,  Konstanze  Kölle1,2,6,  Nils  KrisBan  Skjærvold1,3,7,  Nicolas-­‐Andreas  Elvemo8,    Reinold  Ellingsen1,4,8,  Sven  Magnus  Carlsen1,5,7,  and  Øyvind  Stavdahl1,2  

[email protected]      [email protected]      [email protected]      [email protected]      [email protected]      [email protected]      [email protected]      

MOTIVATION  Animal  trials  •  3  anaestheBzed  non-­‐diabeBc  pigs  •  Intravenous  infusion  of  glucose  boluses  •  Glucose  level  excursions  within  the  range  5–22  mmol/L  

Sensor  types  used  in  trials  •  Intraarterial  (IA):  OpBcal  interferometric  phenylboronic  acid  based  sensors,  placed  in  the  femoral  artery  [3,4].  

•  Intraperitoneal  (IP):  Using  the  same  sensor    as  in  the  IA  case.  Accessed  from  below  the  umbilicus  through  a  common  port,  directed  to  4  different  posiBons  (Fig.  on  the  right).  2–4  sensors  per  animal.  

•  Subcutaneous  (SC):  Off-­‐the-­‐shelf  amperometric    enzyme-­‐based  (glucose  oxidase)  sensors.  Placed  on    the  belly,  above  the  umbilicus.  

•  Venous  blood  was  sampled  and  analyzed  on  a    blood  gas  analyzer  (BGA)  for  reference  and  calibraBon  of  the  other  sensors.  

CONCLUSION  

Why  intraperitoneal  sensing?  •  Subcutaneous  glucose  sensors:  Slow  response,  poor  robustness  towards  local  Bssue  effects  (mechanical  pressure,  temperature  etc).  

•  Intravascular  glucose  sensors:  Not  pracBcally  possible  outside  of  the  hospital/clinic.  

•  We  need  a  rapid,  accurate  and  robust  glucose  measurement  for  making  a  safe  arBficial  pancreas.  

•  Intraperitoneal  glucose  sensors  may  react  faster  than  subcutaneous  sensors  [1,2],  while  being  more  pracBcally  usable  than  intravascular  sensors.  

Norwegian  University  of  Science  and  Technology  (NTNU),  Trondheim,  Norway  

•  Intraperitoneal  glucose  sensors  can  have  a  substanBally  faster  and  more  disBncBve  response  than  subcutaneous  sensors.  

•  Our  results  indicate  that  IP  sensors  may  react  even  faster  than  previously  shown  [2].  

•  Variable  dynamics  during  the  experiments  +  some  sensors  had  to  be  relocated  -­‐>  Need  to  invesBgate  disturbances  &  sensor  locaBon  in  more  detail.  

[1]  Velho,  G.,  Froguel,  P.,  and  Reach,  G.,  “DeterminaBon  of  peritoneal  glucose  kineBcs   in  rats:   implicaBons  for  the  peritoneal  implantaBon  of  closed-­‐loop  insulin  delivery  systems,”  Diabetologia,  vol.  32,  no.  6,  pp.  331–336,  1989.  

[2]   Burneo,   D.   R.,   Huyeo,   L.  M.,   Zisser,   H.   C.,   Doyle   III,   F.   J.,   and  Mensh,   B.   D.,   ”Glucose   Sensing   in   the  Peritoneal  Space  Offers  Faster  KineBcs  than  Sensing  in  the  Subcutaneous  Space,”  Diabetes,  vol.  63,  no.  7,  pp.  2498–2505,  July  2014.  

[3]  Skjærvold,  N.  K.,  Solligård,  E.,  Hjelme,  D.  R.,  and  Aadahl,  P.,  “ConBnuous  measurement  of  blood  glucose:  validaBon  of  a  new  intravascular  sensor,”  Anesthesiology,  vol.  114,  no.  1,  120–125,  2011.  

[4]  Skjærvold,  N.  K.,  Østling,  D.,  Hjelme,  D.  R.,  Spigset,  O.,  Lyng,  O.,  and  Aadahl,  P.,  “Blood  Glucose  Control  Using  a  Novel  ConBnuous  Blood  Glucose  Monitor  and  RepeBBve  Intravenous  Insulin  Boluses:  ExploiBng  Natural   Insulin   PulsaBlity   as   a   Principle   for   a   Future   ArBficial   Pancreas,”   Interna1onal   Journal   of  Endocrinology,  vol.  2013,  ArBcle  ID  245152,  2013.  

6Helse  Midt-­‐Norge  –  The  Central  Norway  Regional  Health  Authority,  Norway  7St  Olavs  University  Hospital,  Trondheim,  Norway  8GlucoSet  AS,  Trondheim,  Norway  

1ArBficial  Pancreas  Trondheim  –  The  APT  research  group  (www.apt-­‐norway.com)  2Department  of  Engineering  CyberneBcs  3Department  of  CirculaBon  and  Medical  Imaging  4Department  of  Electronics  and  TelecommunicaBons  5Unit  for  Applied  Clinical  Research,  Faculty  of  Medicine  

Hydrogel    sensor  

Incident  light  

Reflected  light  

Read-­‐out  instrument  

Interference  

OpBcal  fiber  

Op<cal  interferometric  sensors  

Sensor  placement  

10 cmIP 10 cm

10 cm10 cm

SC

IAsensor

UL

IPLR

IPLL

IPUR

Glucoseboluses & BGA