Monitoring of Blood Glucose Level

Transcription

1 University of Zagreb Faculty of Electrical Engineering and Computing Biomedical instrumentation Monitoring of Blood Glucose Level Biomedical instrumentation 1/17

2 Outline Introduction Principles of Blood Glucose Measurements Instrumentation for Blood Glucose Measurement and Monitoring Closed Loop Glucose Control Systems for Diabetes Management Support Conclusions Biomedical instrumentation 2/17

3 Principles of Blood Glucose Measurements Electrochemical measurement of glucose Colorimetric method Amperometric method Infrared technology Radio wave technology Biomedical instrumentation 3/17

4 Electrochemical measurement of glucose Use of electrochemical test strips A small drop of blood to be tested is placed on a disposable test strip The strip is inserted into a glucose meter for the glucose measurement. Biomedical instrumentation 4/17

5 Electrochemical measurement of glucose Colorimetric method Photo sensors and a Transimpedance Amplifier (TIA) used for the glucose concentration measurement. The Color Reflectance principle for sensing the color intensity Biomedical instrumentation 5/17

6 Electrochemical measurement of glucose Amperometric method Electrochemical test strip contains a capillary to draw in the solution (blood). Enzyme electrode on test strip contains a reagent - Glucose Oxidase. Glucose undergoes a chemical reaction and the process generates electrons. The charge passing through the electrode is proportional to the concentration of glucose in the solution. Temperature sensitive compensation necessary Biomedical instrumentation 6/17

7 Amperometric method GLUCOSE METER TEST WORKING STRIP PRINCIPLE Biomedical instrumentation 7/17

8 Blood glucose test strips Test strip - biochemical sensor Working electrode: Electrons are produced here during the chemical reaction. This electrode is connected to the current-to-voltage amplifier. Reference electrode: Held at a constant voltage with respect to the working electrode to push the desired chemical reactions. Counter electrode: Supplies current to the working electrode. Biomedical instrumentation 8/17

9 Blood glucose test strips Cross section of the test strip Biomedical instrumentation 9/17

10 GLUCOSE METER BLOCK DIAGRAM Extreme low-power (XLP) operation Two op amps 2x8-bit DAC 12-bit Successive Approximation (SAR) ADC, up to 11 channels Internal EEPROM Inter-Integrated Circuit (I2C ) 16-bit Timer1 GLUCOSE METER BLOCK DIAGRAM embedded system Biomedical instrumentation 10/17

11 Blood glucose meters - Glucometers Medical device used to determine the concentration of glucose in the solution (blood). Glucose concentration is measured in: milligram per decilitre (mg/dl) or millimole per litre (mmol/l) depending on the different regions. Glucometers used for home Blood Glucose Monitoring by people with diabetes. Measurements taken several times a day. Biomedical instrumentation 11/17

12 Blood glucose levels in healthy population The blood glucose levels for an adult without diabetes are: below 100 mg/dl before meals and fasting ( mmol/l) less than 140 mg/dl (7.8 mmol/l) two hours after meals. Long-term glucose test called a hemoglobin A1c, HbA1c, or just A1C. gives average reading over the last 2 3 months. HbA1c is expressed as a percentage. Normal for a person without diabetes is below 5.7%. Targets for a person with diabetes are 7.0% or lower. Biomedical instrumentation 12/17

13 Blood glucose levels in healthy population Biomedical instrumentation 13/17

14 Blood Glucose Meters A glucose meter is used to determine the approximate concentration of glucose in the blood. The glucose meter is a key element in monitoring diabetes can help test if the blood sugar is too high or low. Glucose meters are small and are handheld, they can fit in the palm of a hand. Glucose meters cost anywhere from $20 to the most advanced meters costing $500.

15 Blood glucose meters Measurements Glucose measurement range: 20 mg/dl to 600 mg/dl (1 mmol/l to 33 mmol/l) Volume: μm of blood Reading time: 3-5 s Memory capacity: up to 2000 measurement results Software Organizing Presentation Basic analysis Sharing measurement results with health professionals Biomedical instrumentation 15/17

16 Invasive Glucometer (Current) Present day best way blood sugar level accuracy Problems: 1. Can be painful 2. Messy 3. Costly 4. Average number of tests a day is 1.6, compared to the recommend 4 times a day

17 COMMUNICATION IMPROVES HEALTH

18 COMMUNICATION IMPROVES HEALTH

19 COMMUNICATION IMPROVES HEALTH

20 Continuous blood glucose monitoring - CGM Systems continuously track glucose level without patient intervention reveals short-term trends in the blood sugar as they happen in the last 1, 3, 6, 9, 12, or 24 hours Comprises of: A sensor Processing and transmission unit Display unit monitor (or insulin pump) Sensor inserted under the skin, needs to be: Replaced every 7 days (approx.) Calibrated using a standard glucometer Glucose level measured every 1-5 min Measurement results transmitted wirelessly to the disply unit Biomedical instrumentation 20/17

21 Dexcom STS Monitor Readings every 5 min days of readings per sensor One high and two low alerts Transmitter ~0.8 x 1.5 From: Healthcare Across Borders - September 2003 The sensor: thin, flexible wire inserted beneath the skin with a needle and an insertion device. rests in the fatty layer below the skin sensor wires vary from 1/4 to 3/5 inch (6 to 15 mm) in length. contain enzymes that react with glucose in the interstitial fluid chemical reaction produces an electric signal transmitter sends to the CGM receiver

22 Medtronic Paradigm RT FDA release: 4/13/06 Paradigm 522/722 pump Sensor connected to transmitter by wire Approved for 18 and older One high and one low alert Approved for 18 and older One high and one low alert rend arrows Readings every 5 min. From: Healthcare Across Borders - September 2003 NOT a closed loop

23 Insulin pumps Best physiological method for insulin therapy Bazal insulin continuous insulin, 24/7, same as pancreas in healthy population Bolus insulin - on demand insulin, mealtime MiniMed640G Paradigm Veo

24 Insulin pumps Biomedical instrumentation 24/17

25 Insulin pumps Normal Pancreas Pump Basal/Bolus Basal Bolus

26 Artificial pancreas Closed loop glucose control systems Insulin pump Continuous blood glucose monitoring Algorithm for BGL control Biomedical instrumentation 26/17

27 Insulin delivery Skin Subcutaneous Tissue Cannula Insulin 27

28 Evolution of closed blood glucose control systems 28

29 Evolution of blood glucose monitoring 29

30 Evolution of blood glucose monitoring 30

31 Future trends - Non-Invasive Glucometer Infrared Technology: 1. Finger or Earlobe goes into the slot 2. Uses near-infrared light to measure real-time blood glucose levels 3. Takes 20 seconds or less attempted using both near and middle infrared waves

32 Non-invasive measuring of blood glucose Research for easy and less-invasive way to measure glucose daily: tears, airway mucus, sweat, saliva or the interstitial fluid of subcutaneous tissue Biomedical instrumentation 32/17

33 Non-invasive measuring of blood glucose An electronic skin patch that senses excess glucose in sweat and automatically administers drugs by heating up microneedles that penetrate the skin. See also: Hyunjae Lee et al., A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy, Nature Nanotechnology, 2016 Biomedical instrumentation 33/17

34 CGM technology Classifcation of various CGM technologies according to their (a) invasiveness and (b) transduction mechanism of the sensor. Code defnitions in Figure 1A correspond to the respective transduction mechanisms shown in Figure 1B. The asterisk in Figure 1a displays code defnitions corresponding to the detection technologies shown in Figure 1B. For example, code E-1-a corresponds to electrochemical (E) detection based on enzymatic (1) reaction that is oxygen mediated (a) Biomedical instrumentation 34/17

35 CGM technology Biomedical instrumentation 35/17

36 Clinical decission support systems Overview of the CGM data communication bridge architecture Biomedical instrumentation 36/17

37 Clinical decission support systems Biomedical instrumentation 37/17

38 Diabetes Eco-system Biomedical instrumentation 38/17

39 Thank you for your attention! Biomedical instrumentation 39/17

40 Blood glucose monitor block diagram Biomedical instrumentation 40/17

41 Various modes of electrochemical detection of glucose: (A) frst-generation biosensors based on the use of natural oxygen cofactor, (B) second-generation biosensors based on artifcial redox mediators, (C) third-generation biosensors based on direct electron transfer between GOx and the electrode, and (D) direct electrooxidation of glucose Biomedical instrumentation 41/17

42 Biomedical instrumentation 42/17

43 Optical detection of glucose based on (A) fluorescence intensity decrease as a result of affnity binding and (B) decrease in FRET-induced fluorescence intensity Biomedical instrumentation 43/17

44 Typical Meal Bolus Patterns Biomedical instrumentation 44/17

45 Comparison of Standard and Continuous Glucose Monitoringaugmented Automated Bolus Calculator with Prediction Capacity Biomedical instrumentation 45/17

46 Biomedical instrumentation 46/17

47 Biomedical instrumentation 47/17