gSense, a non-invasive glucose measuring device. This

Lumen Medical Technologies Inc. 1154 Harold Rd. North Vancouver, B.C. V7K 1G3

March 7, 2006 Dr. Andrew Rawicz Simon Fraser University 8888 University Drive Burnaby, BC V5A 1S6 Re: ENSC 440 Design Specification for a Non-invasive Glucose Measuring Device Dear Dr. Rawicz, Attached is a document from Lumen Medical Technologies Inc. that lists a set of technical guidelines for design of gSense, a non-invasive glucose measuring device. This document is the Design Specification for our ENSC 440 project. We are in the process of designing and building a device that provides a fast, simple and non-invasive method for detecting and measuring the sugar level in a test solution. We believe that this technology can be a solid foundation for a handheld device that can help patient who suffer from diabetes enormously. The objective of this document is to describe design considerations needed for the successful completion on the project by April of 2006. The design specifications illustrated in this document apply to the proof-of-concept model only. Improvements in design for future versions of the gSense are discussed, but will not be implemented at this stage of development. Lumen Medical Technologies Inc. is made of six innovative senior level undergraduate engineering students. The team members include Mehdi Abdollahi, Deema Annyuk, Jeff Chen, Connor Gillan, Graham Laverty and Tony Tsai. If you have any questions or concerns, please feel free to contact me by phone at (604) 319-4726 or by email at [email protected]. Sincerely, Mehdi Abdollahi Chief Executive Officer Lumen Medical Technologies Inc. http://www.lumen.co.ca Enclosure: Design Specification for a Non-invasive Glucose Detection Device

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http://www.lumen.co.ca/

Design Specification for a Noninvasive Glucose Measuring Device

Project Team: Mehdi Abdollahi Deema Annyuk Jeff Chen Connor Gillan Graham Laverty Tony Tsai Contact Person: Mehdi Abdollahi [email protected] Submitted to: Dr. Andrew Rawicz – ENSC 440 Steve Whitmore – ENSC 305 School of Engineering Science Simon Fraser University Issued Date: March 6, 2006 Revision: 4.0

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Executive Summary Canadian Diabetes Association called the state of the diabetes in Canada as “an epidemic” in its 2005 report [1]. It puts the number of Canadians living with some sort of diabetes at over two millions. An essential step towards controlling diabetes is monitoring the patients blood sugar level frequently. The monitoring devices currently available in the market today require patients blood samples, which make the whole procedure inconvenient and painful. We, at Lumen Medical Technologies, believe that with innovative solutions, it is possible to build a device that can measure a patient’s blood sugar level without the need for any blood samples. This will help those suffering from diabetes immensely. This document outlines the design of the gSense. The main idea behind our design is Radio-Frequency Spectroscopy, in which a source of high frequency electromagnetic radiation is coupled to a specimen containing the glucose. The presence and concentration of glucose is determined by the spectral signature, which is measured from the resulting signal. The result is then to be displayed through an LCD screen. Development of gSense will take place in two phases. After completion of the first phase, gSense will be able to detect and measure the concentration of glucose in a test solution. The development period of the prototype phase is targeted for completion by the middle of April of 2006. For the second phase of development, gSense will also be able to measure the concentration of glucose in human blood through body contact. An ideal future version of this product will be available in a size of a wrist watch.

Copyright © 2006, Lumen Medical Technologies Inc. iii

Table of Contents EXECUTIVE SUMMARY ...................................................................................................................................... III 1. INTRODUCTION..............................................................................................................................................1

1.1 SCOPE..........................................................................................................................................................1 1.2 ACRONYMS .................................................................................................................................................1 1.3 INTENDED AUDIENCE ..................................................................................................................................1

2. SYSTEM OVERVIEW......................................................................................................................................2 3. SYSTEM HARDWARE ....................................................................................................................................3

3.1 VOLTAGE REGULATOR................................................................................................................................3 3.2 OSCILLATOR................................................................................................................................................3 3.3 THE BAND-PASS FILTER UNIT.....................................................................................................................3 3.4 GAIN AND PHASE DETECTOR ......................................................................................................................5

3.4.1 Connections ...........................................................................................................................................6 3.4.2 Response Characteristics.......................................................................................................................6

3.5 ANALOG-TO-DIGITAL CONVERTER, W/ON-CHIP LCD DRIVERS ..................................................................7 3.6 DISPLAY......................................................................................................................................................7

4. SYSTEM TEST PLAN ......................................................................................................................................8 4.1 NOISE ANALYSIS .........................................................................................................................................8 4.2 THERMAL ANALYSIS ...................................................................................................................................9 4.3 POWER ANALYSIS .......................................................................................................................................9 4.4 PHYSICAL CONNECTIONS ............................................................................................................................9 4.5 RELIABILITY/DURABILITY/MISUSE ...........................................................................................................10 4.6 CONCENTRATION READING RELIABILITY ANALYSIS.................................................................................10

APPENDIX A – SCHEMATICS..............................................................................................................................11 REFERENCES ..........................................................................................................................................................14

Copyright © 2006, Lumen Medical Technologies Inc. iv

List of Figures FIGURE 1 - SYSTEM BLOCK DIAGRAM............................................................................................................................2 FIGURE 2: PACKAGE DIMENSIONS FOR DIGIKEY [3] ......................................................................................................3 FIGURE 3 – TRANSFER FUNCTION FOR BPF....................................................................................................................4 FIGURE 4 – FREQUENCY RESPONSE OF BPF....................................................................................................................5 FIGURE 5 – AD 8302 FUNCTIONAL BLOCK DIAGRAM [8] ...............................................................................................5 FIGURE 6 – IDEAL TRANSFER CHARACTERISTICS OF AD8302 [8] ..................................................................................6 FIGURE 7 – TYPICAL CONNECTIONS FOR TC7129 [9].....................................................................................................7 FIGURE 8 – DIAGRAM OF VIM-502 DISPLAY [10]. .........................................................................................................8

Copyright © 2006, Lumen Medical Technologies Inc. v

1. Introduction At Lumen Medical Technologies Inc., it is our goal is to provide diabetics with a clean, easy and pain-free way of testing their blood sugar levels. gSense is a non-invasive device that will measure the concentration level of glucose in a test solution. Future versions of this device will be able to measure the level of glucose in a diabetic patient without the need for any blood samples, requiring only touch. This design specification explains the technical details for the design of each component of gSense.

1.1 Scope This document describes the design of gSense and explains how the design meets the functional requirements as described in Functional Specification for a Non-Invasive Glucose Measuring Device [2]. A full set of design requirements is supplied for the proof of concept device. The design requirements for the generic version of the device are simplified compared to the production device since we believe that substantial experience will be gained during the development of the proof of concept.

1.2 Acronyms A/D Analog-to-digital BPF Band-Pass Filter CSA Canadian Standards Association CU Computation unit DIP Dual Inline Package EMI Electromagnetic interference IC Integrated circuit I/O Input/output LCD Liquid crystal display LED Light-emitting diode PCB Printed circuit board PPM Parts per millions

1.3 Intended Audience This document is intended to be a guideline for all members of Lumen Medical Technologies Inc. It also supplies potential customers or investors with the product specifications as experienced by the end user. The project manager will refer to this document in order to measure progress throughout the development phase. Design engineers will use this document to ensure all of the design goals are propagated from the product design stage to the implementation phase.

Copyright © 2006, Lumen Medical Technologies Inc. 1

2. System Overview All molecules and elements have a specific radio frequency disturbance pattern. That is when a specimen is targeted with a known frequency of electromagnetic radiation, or range of frequencies, the specimen will produce a predictable response spectrum. Characteristics of this signal include a frequency targeted at approximately 30MHz, with rise and fall transition times less than about 10 ns, a duty cycle of about 50%, and a power level in the range of about 0 dBm to +10 dBm. Possible changes in spectra include changes in frequency distribution, and changes in signal amplitude. The source signal is compared to the return/output signal and the change will show the concentration of the specified compound. In the case of Diabetes the target compound is glucose. Radio Frequency Spectroscopy has the benefits of being completely noninvasive, and providing a good sensitivity for glucose. This technique is patented by Fuller and Cherne, US Patent #5508203 [5]. A block diagram of our system is shown below (Figure 1).

Figure 1 - System Block Diagram

Oscillator Receiver

Transmitter

BP filter

Amplifier

Amplifier

Phase/Gain comparator

LCD Display

ADC/LCD Driver

BP filter

Amplifier


3. System Hardware

3.1 Voltage Regulator To ensure that all active components in our design are powered by constant voltage level a voltage regulator is used. We have chosen ADP667AN-ND voltage regulator because it comes in a DIP packaging, which is very convenient during the development stage. We were also able to get free samples from Analog Devices Inc. This particular regulator is a low-dropout precision voltage regulator and can supply up to 250 mA of output current. It is normally used to produce fixed +5V output without additional components. It can be easily modified to produce fixed voltage from +1.3 to +16V with 2 additional external resistors. The operational temperature range of -40˚C to +85˚C meets the requirement of the functionality specification [6].

3.2 Oscillator We require a high frequency signal with a very wide spectra, such as a square wave. We selected a square wave oscillator based on its performance. We need a nanosecond rise and fall time and 50% duty cycle. This square wave will be sent to the sample solution through the transmitter and processed by an amplifier, and phase/amplitude detect mechanism. The chosen oscillator has a maximum rise and fall time of 5ns. The oscillator has +/- 100ppm frequency stability [4]. This oscillator is fully compatible with TTL circuitry. The oscillator is also inexpensive, costing about $2.50 CAD, or less with volume."

Figure 2: Package Dimensions for DigiKey [3]

3.3 The Band-Pass Filter Unit The preliminary function of the band-pass filter (BPF) is to transmit the test signal that comes from the testing solution for further analysis and to exclude signals in lower and higher frequencies. The center frequency of the BPF is equal to the generated frequency of the oscillator and has a bandwidth of 1 kHz. The bandwidth can be increased (up to 1MHz) if necessary [5].


The simplest way of implementing a BPF is to use passive structures rather than active ones. Passive filters are designed completely using passive components (resistors, capacitors and inductors) and are simple to design, but are a bit challenging to implement. Implementation challenges are due to limited part value range availability. Even thought the passive filter is simple and uses passive components, which are inexpensive, it has several disadvantages. The passive filter cannot provide signal gain and therefore will require a preamplifier when working with weak signals. Problems can arise from poor impedance characteristics, because the input impedance of the filter is too low and output impedance is usually too high. The inductors which are essential parts of passive filters introduce the problem of desired and available component values and can be expensive if high accuracy components are used. Inductors, have many wire windings that introduce resistance loss, which can degrade the circuit performance. Finally the problem we have encountered is that passive filters are time consuming and difficult to design, because we require high center frequency with relatively narrow bandwidth. For the reasons stated above we decided to use an active filter (Appendix A). The active filters (when compared to passive ones) are generally easier to design and to implement. They also produce less signal loss than passive ones. Active filters provide high input and low output impedances. Another advantage when using active filters is the ability to implement signal gain without additional components. Finally active filters do not use inductors thus eliminating the impedance problem discussed above. The BPF in our design is required to have 30MHz center frequency and bandwidth from 1 kHz up to 1 MHz. Based on these requirements, the following design for BPF is produces which is presented in Appendix A. The circuitry for the BPF is constructed using 3 high speed operational amplifiers (LT1224). This particular operational amplifier was chosen because it is high speed (45 MHz gain-bandwidth) which is well above our operational frequency. It also has fast slew rate (400 V/μs), has wide supply range: ±2.5V to ±15V and requires only 7 mA of current [7]. The last point is important because our design will eventually be battery power. The circuit will be powered with ±5V which is be provided by a voltage regulator (ADP667AN-ND). In a later stage when the design will be implemented on PCB surface mount 0.1% tolerance resistors and capacitors will be used. The transfer function and frequency response are given in Figure 3 and Figure 4 respectively.

Figure 3 – Transfer Function for BPF


Figure 4 – Frequency response of BPF

3.4 Gain and Phase Detector As mentioned in the Spectroscopy theory section above, gSense is based on the theory that as a Radio Frequency signal, centered at 30Mhz, is passed through a solution its gain and phase will change. We need to compare the reference transmission signal that is passed to the solution with that coming out of it. This can be accomplished using phase locked loops and comparators, but we have found an integrated solution from Analog Devices, the AD8302 RF/IF Gain and Phase Detector. This chip was chosen for its ability to integrate 2 required sections of our design. It is available in the TSSOP 14 package, and 4 were acquired from Analog Devices Inc. for free, as part of their new design initiative. A functional block diagram is shown below.

Figure 5 – AD 8302 Functional block Diagram [8]


The AD8302 is a fully integrated system for measuring gain/loss and phase in a variety of applications. It requires few external components and a single supply of 2.7-5.5V, and will draw from 19-25mA. The input frequency can range from 0 to 2.7 GHz. The outputs provides` a measure of gain/loss over a range of +- 30dB at 30mV/dB. It also provides an output related to phase change over 0-180 degree range, at 10mV/degree. These outputs are simultaneously available, and provide an output range of 0-1.8V [8].

3.4.1 Connections The 8302 requires very few peripheral components, as in Appendix A, Gain and Phase Detector, with appropriate component values. VinA and VinB are the two signals to be compared, Vmag is the gain output, and Vphs is the phase difference output.

3.4.2 Response Characteristics Vmag and Vphs are related by the following relationships, where is the gain slope of 600mV/decade, or 30mV/dB

slpf IR[8].

At low frequencies in this measurement mode the idealized transfer characteristics are as shown in the figure below.

Figure 6 – Ideal Transfer Characteristics of AD8302 [8]


3.5 Analog-to-Digital Converter, w/on-Chip LCD Drivers In order to show a measure of change in glucose concentration we need to have a display. Displays that show numbers usually require some kind of driver circuit and an analog to digital converter. To further reduce the number of chips gSense requires we have been able to locate the TC7129 integrated 4-1/2 digit Analog-to-Digital Converter with On-Chip LCD Drivers, from Microchip Technology Inc. This chip is an excellent choice as it has low power consumption (500uA at 9V) and is able to directly drive most 4-1/2 digit multiplexed LCD displays. We have also been able to procure some free samples from Microchip. This ADC/Driver only requires a few peripheral passive components to function, and can be powered from 3.8-15V DC. This ADC/LCD driver is designed for battery powered digital multimeters, a similar application to ours. An important feature of this chip for us is its ability to also detect and display a low battery condition, it can also attach to an annunciator to give an audio signal to a low battery condition. A typical application of this device is shown below.

Figure 7 – Typical Connections for TC7129 [9]

3.6 Display We have chosen to use the VIM-503-2 LCD display from Varitronix International Limited. It is a direct connection to the TC7129 A-D/LCD driver. This is a good choice for this project as it is a high contrast, low power display that is able to also display a low battery condition. This display is shown in the figure below.


Figure 8 – Diagram of VIM-502 Display [10].

4. System Test Plan To ensure that gSense is as accurate and versatile a device as possible, we will need to conduct testing in several different key areas. Many of these test cases are important even for the proof of concept to ensure an accurate baseline for our readings, whereas the rest are required for the production design, before the manufacturing process to ensure a trustworthy, stable, accurate final product. This test plan is not intended to be completely comprehensive nor restrict further testing, but to ensure a baseline for tests to be performed and extended upon.

4.1 Noise Analysis Since our unit emits and produces analysis on radio frequencies, this will be an important area to test. Since gSense is a very “local area” device (measuring the RF output over only a short distance) we expect interference caused by the device to be minimal, but we will need to test it to make sure it falls within an acceptable range. However, what concerns us more is the systems response to external noise, especially due to its low power signals. Specifically, we want to subject the unit to artificial interference and high levels of white noise. We want to make sure that this causes minimal degradation of the unit and in particular does not cause the unit to take significantly incorrect readings. If the filter proves insufficient to protect the unit from interference adequately to continue to take accurate readings, additional compensation (such as shielding or even having the unit simply refuse to take a reading until background interference drops to reasonable levels) will be required.


We also want to test for crosstalk of our circuit. We will do this by, for example, feeding an input signal into one channel while others are disable/unplugged and see how the rest of the circuit responds. It is expected that our shielded twisted pair wires will be able to minimize most of this.

4.2 Thermal Analysis During proof of concept phase, the temperature of the glucose solution will be subjected to different test ranges (from very cold but above 0°C to very hot but below 100°C). It will then be observed if different temperatures in the reagent generate different readings. If so, the design will be modified to incorporate a temperature sensor to allow it to compensate for readings. The production model will likely incorporate a temperature sensor, anyway, to notify the user when the user is attempting to use it outside of its rated temperature range. During the prototyping phase, the operating test range of the prototype will be tested at multiple temperatures, and in particular at both ends of its operating range. This should not have any effect on its readings but it is necessary to test and determine its full operating range.

4.3 Power Analysis The proof of concept is expected to be powered primarily using wall AC-DC adapter, whereas the production model is expected to be battery powered. As such, we will have to test each of them during each phase. For AC, we will want to test for “dirty” power (where the power supply introduces voltage spikes, uneven frequency, other loads on the same circuit that keep coming on and offline, current limits, etc) and make sure that not only does the unit respond as gracefully as possible to these, but in particular that the power interference it does not introduce any significant signal interference into the rest of the circuit. Specifically we will want to test for voltage regulation, the input range, voltage abnormalities and spikes, and artificial noise produced by the power supply. Battery life should also be tested to ensure a reasonable operating life. (The design could be adapted to use less power or require more batteries should the existing design consume too much power).

4.4 Physical Connections All the physical connections for all the parts must be ensured, including connections of all IC components to the PCB, all parts with each other, and so on. We also want to ensure component placement is done in such a way as to minimize component interference with each other. During proof of concept, such testing is fairly evident (for the unit to work at all), and for manufacturing there are industry-standard QA tests. Our component layout is very basic, and no unusual component testing is expected, although we want to ensure all components are securely seated and connected such that any vibration/bumps a portable pocket-size unit could be subjected to



are not likely to severe any of these connections. This will be discussed in greater detail during the reliability section.

4.5 Reliability/Durability/Misuse This will be particularly important before manufacturing production versions of the device. We will want to intentionally subject our design to a great variety of external abuse, misuse and minor damage (such as dropping onto the floor or bumping against a table). The unit’s parts should all be firmly in place and the unit should not be caused to fail within a degree of reasonable use to insure that it will last throughout at least the warranty period with no failures. We will also want to test for possibilities of misuse. A simple design should minimize most of these, but we want the unit to be easy to use, and hard to misuse through improper usage or service. We also want to insure the unit performs well during continuous use. If the unit performs measurements virtually none-stop this may cause the unit to heat up, which in turn can affect other measurements and possibly cause certain components to overheat and fail. Should any of these be a “problem”, they are not necessarily a failure, but the unit should limit the frequency of tests to ensure that none of the components should be overused (twice a minute for example).

4.6 Concentration Reading Reliability Analysis The proof of concept will focus primarily on being able to show different readings for different glucose measurements. Before producing the production prototype, however, we will have to focus on being able to convert those readings into meaningful quantitative measurements. We will have to test a wide range of glucose concentrations in test tubes, subject to different temperatures, humidity, noise, etc. to make sure we can produce consistent readings. Most of the other tests focus on minimizing interference and noise, and many of these will be done first to minimize their effects on the results. We will then have to repeat these on human subjects which may have their own “interference”, and still be able to produce consistent readings. Since different humans may have their own individual baselines based on age, blood volume, and other biological factors, the unit may require individual calibration on a per-user basis. Although the focus of the testing will be eliminating this requirement (having a “universal” unit would be much more desirable), this is an acceptable restriction, especially for our first production model. However, being able to have enough of a baseline that the number of measurements required for reliable and accurate calibration can be minimized (and ideally performed without technical staff) would also be a focus on this section. Any environmental conditions (such as temperature of the unit, temperature of the subject, even humidity or static) that may affect such measurements should be tested and compensated for (such as by adding additional sensors).

Appendix A – Schematics

Amplifier Circuit


Band-pass Filter


Gain and Phase Detector [8]



References [1] Canadian Diabetes Association, Diabetes Report, 2005. [online]. Available: http://www.diabetes.ca/section_advocacy/index.asp [accessed: January 20, 2006] [2] Lumen Medical Technologies Inc., “Functional Specification for a Non-Invasive Glucose

Measuring Device”, Simon Fraser University, Burnaby, BC, Canada, January 2006. [3] DigiKey Corporation, DigiKey XC316-ND data sheet. [online]. Available: http://dkc3.digikey.com/PDF/T061/0910.pdf [accessed: March 3, 2006] [4] ECS Inc. International, Clock Oscillator Application Notes.

[online]. http://www.ecsxtal.com/pdf/clock_app.pdf [accessed: March 3, 2006]

[5] FreePatentsOnline. Patent 5508203

[online]. http://www.freepatentsonline.com/5508203.html [accessed: March 4, 2006] [6] Analog Devices, Voltage regulator ADP667AN [online]. http://www.analog.com/en/prod/0%2C2877%2CADP667%2C00.html [accessed: March 4, 2006] [7] Linear Technologies, High Speed Operational Amplifier

[online]. http://www.linear.com/index.jsp [accessed: March 4, 2006] [8] Lf-2.7 GHz RF/IF Gain and Phase Detector, AD8302 Analog Devices, Inc., 2002 [9] 4-1/2 Digit Analog-to-Digital Converters with On-Chip-LCD Drivers Microchip Technology Inc., 2002 [10] VIM-503-2 Display Varitronix International Limited, 2004

http://www.freepatentsonline.com/5508203.html

http://www.analog.com/en/prod/0%2C2877%2CADP667%2C00.html

http://www.linear.com/index.jsp

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gSense, a non-invasive glucose measuring device. This