WO2016154762A1 - Portable detection device - Google Patents

Portable detection device Download PDF

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Publication number
WO2016154762A1
WO2016154762A1 PCT/CA2016/050385 CA2016050385W WO2016154762A1 WO 2016154762 A1 WO2016154762 A1 WO 2016154762A1 CA 2016050385 W CA2016050385 W CA 2016050385W WO 2016154762 A1 WO2016154762 A1 WO 2016154762A1
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WO
WIPO (PCT)
Prior art keywords
detection device
portable detection
magnetic
communication
signal
Prior art date
Application number
PCT/CA2016/050385
Other languages
French (fr)
Inventor
Woohyuk LEE
Jeong-Kook PARK
Samuel LEGGE
Original Assignee
Insight Diagnostics Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Insight Diagnostics Inc. filed Critical Insight Diagnostics Inc.
Publication of WO2016154762A1 publication Critical patent/WO2016154762A1/en

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Classifications

    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04MTELEPHONIC COMMUNICATION
    • H04M1/00Substation equipment, e.g. for use by subscribers
    • H04M1/72Mobile telephones; Cordless telephones, i.e. devices for establishing wireless links to base stations without route selection
    • H04M1/724User interfaces specially adapted for cordless or mobile telephones
    • H04M1/72403User interfaces specially adapted for cordless or mobile telephones with means for local support of applications that increase the functionality
    • H04M1/72409User interfaces specially adapted for cordless or mobile telephones with means for local support of applications that increase the functionality by interfacing with external accessories
    • H04M1/72412User interfaces specially adapted for cordless or mobile telephones with means for local support of applications that increase the functionality by interfacing with external accessories using two-way short-range wireless interfaces
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6887Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient mounted on external non-worn devices, e.g. non-medical devices
    • A61B5/6898Portable consumer electronic devices, e.g. music players, telephones, tablet computers
    • H04B5/24
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04WWIRELESS COMMUNICATION NETWORKS
    • H04W84/00Network topologies
    • H04W84/18Self-organising networks, e.g. ad-hoc networks or sensor networks
    • H04W84/20Master-slave selection or change arrangements
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04WWIRELESS COMMUNICATION NETWORKS
    • H04W88/00Devices specially adapted for wireless communication networks, e.g. terminals, base stations or access point devices
    • H04W88/02Terminal devices
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04MTELEPHONIC COMMUNICATION
    • H04M2250/00Details of telephonic subscriber devices
    • H04M2250/02Details of telephonic subscriber devices including a Bluetooth interface

Definitions

  • US patent applications 2012/0130646 to Landis and 2010/0000862 to Rao disclose detection kits that work in combination with cell phones.
  • the detection system of Rao connects to the end of the cell phone and thus extends the length of the cell phone, which may be inconvenient, and the system of Landis is not directly connected to the cell phone and thus must thus be carried separately.
  • the systems of Landis and Rao use conventional wireless communication such as Bluetooth or a wired connection.
  • communication between the master and slave devices are essential for data management.
  • a medical device can be made into a handheld size if the core functionality of the medical devices is kept as succinct as possible while eliminating other generic features of hardware (e.g. display, data storage, data analysis etc.), as long as the device (or a module) can communicate the critical information to the master device (e.g. computers, smartphones, tablet PC).
  • wired communication protocols include universal serial bus (USB) and audio jack.
  • USB universal serial bus
  • audio jack audio jack
  • wired communication protocols require a wire to be connected between the master and slave device.
  • USB universal serial bus
  • both the devices require a program that is configured to transmit and receive the specific type of data coming from a communication protocol.
  • a user needs to plug in a wire (e.g. USB cable or audio jack) into the devices. If at least one of the devices have plugs that are not compatible with the wire, then either the wire or connector need to be redesigned to fit into the existing devices.
  • Wireless communication protocol such as Bluetooth, Zigbee, or Wi-fi does not require wires, and therefore considered as more convenient for users. However, it still needs a specific configuration that can transmit and receive the data communicated in each protocol. The long distance that these communication protocol travels is potentially dangerous because the communication can be interrupted or hacked by an external device that are configured to receive and transmit information without authorization. Synchronization process for these protocols is required for the communication between two devices to occur, and this could add another complication for users to use wireless communication protocols.
  • near-field magnetic induction uses resonance between two coils, one in each device between which the communication occurs.
  • the need to have such hardware in both devices makes it unsuitable for communication with an off-the-shelf consumer product.
  • a communication system for communicating between a slave device and a master device, the master device having a non-coil magnetic sensor and having a microprocessor programmable to process input from the magnetic sensor, the communication system comprising a magnetic coil in the slave device for generating a magnetic field, and a controller in the slave device configured to control the magnetic coil to modulate the magnetic field to represent data to be transmitted to the master device, the modulation of the magnetic field being detectable by the magnetic sensor when the slave device is located in proximity to the master device.
  • the magnetic coil may modulate the magnetic field by turning on and off, the magnetic coil may modulate the magnetic field by emitting positive, negative, and 0 magnetic field, there may be plural magnetic coils in the slave device oriented to produce respective magnetic fields in different directions, the magnetic sensor being able to distinguish modulation of the magnetic field in the different directions, data may be represented using the magnitude of the magnetic field, and data may be represented using a time difference in "on" mode and "off mode.
  • the portable detection device comprising: a communication system as described in any of the above embodiments, a detection part adapted for generating an electrical signal upon detecting an electrochemically active species, and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part.
  • the portable detection device may be embedded in a cover for the smartphone, the detection part may comprise an electrochemical cell having electrodes and a potentiostat circuit for supplying stable voltage input at the electrodes, the portable detection device may have a digital to analog converter for converting a digital signal from the microcontroller to an analog signal applied to the electrodes, the portable detection device may have a current to voltage converter followed by analog to digital converter for converting current appearing at the electrodes to a digital signal to be processed at the microcontroller, the smartphone may have a local communication part and the portable detection device may have a
  • the local communication part for communicating with the local communication part, and the local communication part may comprises a Bluetooth wireless communication port
  • the detection part may comprise interdigitated electrodes and a bipotentiostat circuit
  • the detection part may comprises a rotating disk electrode and bipotentiostat circuit
  • the detection part may incorporate a microfluidic chip
  • the microfluidic chip may comprise one or more of a glucose strip and immunoassay chip
  • the detection part may incorporate a microfluidic chip holder
  • the portable detection device may have an installed power source
  • the portable detection device may have a lancer attached to the portable detection device
  • the portable detection device may have a chip pocket attached to or forming part of the portable detection device.
  • the portable detection device comprising a communication system as described in any of the embodiments described in the first paragraph of this summary, a detection part adapted for generating an electrical signal upon detecting an electrochemically active species, and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part.
  • the portable detection device comprising a communication part adapted for wireless communicating with the local communication part; a detection part adapted for generating an electrical signal upon detecting an electrochemically active species; and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication part and the detection part.
  • the portable detection device may be embedded in a cover for the smartphone, and may incorporate various types of electrochemical cells, microfluidic chips, various types of potentiostats, converters, various types of electrodes, and an installed power source.
  • a portable detection device for communicating with a handheld computing device having a local communication part.
  • a smartphone is configured to control the portable detection device.
  • a method of detecting an electrochemically active species comprising operating a smartphone to control the portable detection device.
  • Figure lAto IF illustrates a smartphone cover embedded with an electrochemical detection circuit with a chip holder.
  • Figure 2Ato 2D illustrates exemplary (bi)potentiostat schematics embedded in the smartphone cover.
  • Figure 2E illustrates a flow diagram of how the electrochemical detection system circuit works.
  • Figure 3A illustrates an exemplary result of cyclic voltammetry curve (and calibration curve) that can be obtained from the device.
  • Figure 3B illustrates an exemplary result of a calibration curve to determine correlation between electronic peak signal from CV and concentration of an electrochemical active specie (pAP is used in this example).
  • Figure 4 illustrates an exemplary flow diagram for smartphone application software, (how the data is collected, processed, and managed from the electrochemical detection system to a smartphone device).
  • Figure 5 is a graph showing an example magnetic field produced by a coil near a smartphone as detected at a magnetic field sensor of the smartphone.
  • Figure 6 is a graph showing an example magnetic field and an example threshold for threshold-based signal processing.
  • Figure 7 is a graph of signal value resulting from processing based on the threshold in Figure 6.
  • Figure 8 is a graph showing an example of changes in a magnetic field and positive and negative thresholds for magnetic field changes.
  • Figure 9 is a graph of signal value resulting from processing changes in the magnetic field strength according to thresholds in Figure 8.
  • Figure 10 is a diagram showing an electrochemical detection circuit using a magnetic coil to communicate to a smartphone.
  • Figure 11 is a diagram showing an electrochemical detection circuit using a magnetic coil and a conventional communication system such as Bluetooth to communicate with a smartphone.
  • Magnetic communication enables one-way (typically from slave to master) wireless communication over a distance of a few centimeters (max -lOcm) as long as the slave device has inductive coil as a transmitter and the master device with embedded magnetic sensor(s).
  • This type of communication is especially useful in setting up a wireless communication protocol between mobile devices such as smartphones and tablet PCs and an attached hardware accessory.
  • Magnetic communication travels over a short distance because the magnitude of magnetic field decreases significantly. The possibility of hacking the signal is limited by the distance that the communication can travel. In order for someone to hack into the signal, the hacking device need to be physically placed on top of the slave device (with distance less than 10 cm), which emits the signal.
  • Another advantage of the communication is in its simplicity in implementation on existing mobile device operation system (OS) platforms.
  • Google Android provides an open source algorithm that monitors the magnetic field over a period of time. By monitoring the magnetic sensor, one can easily implement a magnetic communication protocol on Android application. For the transmitting magnetic signal, one can program a microcontroller to turn the signal on and off (in unidirectional or bidirectional) the magnetic coil.
  • the method could also be implemented on other OSs such as iOS, BlackBerry OS, and Microsoft Windows.
  • Example sensors include accelerometer, temperature sensors, gravity sensors, gyroscope, light sensors, accelerometer, magnetometer, pressure sensor, proximity sensor, relative humidity sensors, rotations vector sensors. These sensors are beneficial for making efficient and effective smartphone applications in many different areas such as GPS, compass, digital bubble level, temperature and humidity monitor, smartphone games using accelerometers and others.
  • Magnetic sensors used in consumer devices such as smartphones include Hall effect, giant magnetoresistance, magnetic tunneling junction, anisotropic magnetoresistance, and Lorentz force sensors.
  • the term "magnetic sensor” used in this document may include plural magnetic sensors, for example plural magnetic sensors used to detect magnetic fields in different directions. Plural coils can be used to generate magnetic fields in different directions. In principle, the magnetic fields in the different directions can be separately detected by the magnetic sensor allowing more bandwidth.
  • a copper coil from a hard disk drive is used to drive an electromagnetic field from an electronic signal generated by the device.
  • the voltage is applied across the coil, then the current produced from the potential will cause the magnetic field to appear. If the voltage is off, then there will be no magnetic field from the coil.
  • the copper coil is placed directly underneath the smartphone. In this specific testing arrangement, a Nexus 4 smartphone was used.
  • the coil is small and the circuit is not optimized for magnetic communication, the signal is still weak; therefore, positioning the coil directly under where the magnetometer in the smartphone was important. Otherwise, the magnetic field is not strong enough to display digitized magnetic signal from the magnetometer.
  • Magnetic communication is slower than other types of high frequency communication methods such as Wi-Fi and Bluetooth. As shown in the graph, each signal has a finite slope, and it takes time for the magnetometer to recognize the change in surrounding magnetic field.
  • the communication method used is #2 (delta of magnetic signal). Although it will be ideal to utilize complex signal processing techniques such as AM, FM, FFT or others to maximize the accuracy, the method #2 is simpler to execute, and it has reasonable amount of accuracy.
  • a modified fusion sensor algorithm could be used to compensate the distortion of magnetic field by the movement of smartphone and smartphone case.
  • the magnetic coil communication system can be used, for example, in a portable detection device to communicate with a smartphone as an alternative to or in conjunction with a conventional communication system such as Bluetooth.
  • a purpose of the portable detection device is to utilize mobile phone technology to simplify monitoring needs of everyday individuals.
  • a mobile phone's processing power instead of an on-board processing system with developed graphic user interface (GUI)
  • GUI graphic user interface
  • the device is able to act as an integrated accessory dependent on its "master" mobile device.
  • Development of a mobile application to link the accessory to the mobile device's processor is done via Bluetooth communication.
  • the digital communication processing device encapsulating protective cover is advantageous to currently available monitoring systems for several reasons: cost, user experience and convenience. [0063] Since the device is to be manufactured without significant on-board processing power the device will be significantly less expensive to manufacture, therefore the cost savings can be passed on to the consumer.
  • a monitor is embedded in a mobile device protective cover and therefore it serves a dual purpose of both protecting a customer's mobile device from damage as well as enabling on-the-go monitoring.
  • This dual purpose allows customers to forgo the worry of bringing two devices to their workspace or daily destinations as both a monitor and mobile communication device are now together in one package. For example, diabetics would be able to forgo carrying their required blood sugar monitor with them to their workspace as well as their mobile communication device, due to the two systems being integrated into one unit through the use of this portable detection device.
  • a smartphone cover embedded with an electrochemical detection system comprises in an embodiment two main parts: smartphone cover and an embedded electrochemical detection circuit.
  • the smartphone cover provides cosmetic and shock protection for the encased digital communication device while also integrating a detection system onto any digital communication processor device.
  • a designed detection circuit has components necessary to perform electrochemical analysis, which analyzes chemical component of a liquid sample in the form of an electronic signal.
  • a potentiostat circuit is included in the system for supplying stable voltage input at electrodes of electrochemical cell. The electric potential between reference electrode and working electrode is applied through digital to analog converter (DAC), which converts digital signal from microcontroller to analog signal.
  • DAC digital to analog converter
  • the current at working electrode(s) are measured by current to voltage (i-V) converter followed by analog to digital converter (ADC).
  • ADC analog to digital converter
  • the analog signal is converted to digital signal, that signal is recorded to microcontroller, and the set of data is sent out through wireless communication port (Bluetooth) to a smartphone device, or a magnetic communication system as detailed above.
  • the system is to be further developed to control a sample liquid using electronic signal.
  • electrochemically active species in liquid sample comes into contact with the electrodes upon a certain electric potential, they undergo oxidation and reduction (redox) reaction. During this stage, electrons are transported from the molecule undergoing the redox reaction. This electrochemical reaction can be described by mass transport phenomenon. The more electrochemically active species present in sample, the more electronic signal is generated.
  • the electrochemically active species include, but are not limited to: hydrogen peroxide, ferrocene, ferricyanide, p-aminophenol (pAP), p-nitrophenol (pNP),
  • TMB tetramethylbenzidine
  • the IDA electrode and bipotentiostat can be used to increase sensitivity of signal significantly only if the specie can undergo redox recycling or in other words the redox species reaction is reversible.
  • any type of microfluidic chip can be inserted into the circuit such as glucose strips, immunoassay lab-on-a-chip devices, and white papers.
  • glucose strips are required to monitor glucose level.
  • the strips consist of electrode for
  • microfluidic immunoassay chips can be utilized.
  • the chips consist of a microfluidic circuit with microfluidic valves for automatic liquid handling if liquid handling is necessary, immunoassay reagents, and electrodes.
  • anodic stripping voltammetry should be run on the electrodes while liquid sample is in contact with the electrodes since it is not necessary to have a confined microfluidic channel for liquid handling, as the heavy metal in sample will used directly as the electrochemically active species, unless the heavy metal is selectively captured by antibody or proteins. If concept of selective capturing of proteins is used, then microfluidic circuit with automatic liquid handling can be necessary.
  • An advantage of this portable detection device is that it simplifies the integration of portable electronic devices such as smartphone devices and electrochemical detection system for applications such as glucose monitoring, analyte monitoring, or heavy metal detection.
  • This portable detection device allows consumers to use their smartphones or other portable digital communication device as glucose sensors, point-of-care diagnostic device, heavy metal monitoring device at the point of required detection. This is done for example through simple wireless communication module (for example, Bluetooth) between smartphone and the electrochemical detection circuit.
  • the smart phone comprises both processing capability and two wireless communication parts. One wireless communication part is for communication with a mobile phone network and the other communication part is for local communications, for example Bluetooth. Such devices are ubiquitous. Alternatively other systems can be used for local communication such as the magnetic system detailed above.
  • FIG. lA to IF a case for a portable electronic device with embedded electrochemical detection circuit is provided.
  • Figure lA is the front view
  • Figure IB is the back view
  • Figure 1C is the top view
  • Figure ID is the bottom view
  • Figure IE is the right view
  • Figure IF is the left view.
  • the portable detection device is comprised of a lip 1 that will hold the portable electronic device (e.g. smartphones) and the main body 2 together, and may include a window 3 A for allowing a camera to function while the case is in place on the smartphone.
  • Various other methods may be used to secure the portable detection device on the portable electronic device.
  • the portable detection device also includes a "bump" 4 with a chip/glucose strip holder 5 that will work as an electrochemical detection device.
  • the main advantage of implementing the portable detection device with a portable electronic device such as smartphones is that it provides an added capability to analyze and quantify an analyte of interest in a sample fluid dropped on a chip or glucose strip that will be connected at the chip holder 5.
  • a portable chip pocket 6 and a lancer 3 can also be attached to or form part of the portable detection device to ease carrying apparatus required for point-of-care health monitoring.
  • the chip pocket 6 will house biochips such as glucose strips, microfluidics, or white papers that are capable of measuring and detecting chemical specie in sample fluid when connected to the chip/glucose holder 5.
  • the customer will put in several glucose strips or any other detection chips to the chip pocket 6, and they will be able to monitor their health anywhere, anytime, as long as they carry their smartphones with the invention attached.
  • the lancer 3 can be used for piercing a finger or other human body parts to obtain a drop of blood.
  • Potentiostat device is included in order to enable portable electrochemical detection, (power is to be provided with a conventional battery such as lithium battery, and the bump 4 will have its own cover so that a user can replace the battery when the battery is drained.) Potentiostat device consists of up to four electrodes: reference electrode 100, counter electrode 101, first working electrode 102, and second working electrode 103. Voltage at reference electrode 100 and counter electrode 101 is controlled by operational amplifier 111. When an electrochemical cell is connected, the operational amplifier 111 acts as a voltage follower, and the voltages at nodes 100 and 101 will be the same value as the voltage at node 104, regardless of what is happening within the electrochemical cell.
  • an additional voltage follower 114 can be added to minimize the current flow at reference electrode 100 as shown in Figure 2D.
  • Input voltage 104, 105, 108 for voltammetry testing is sent from the microcontroller as an analog signal through analog-to-digital (ADC) signal conversion.
  • ADC analog-to-digital
  • voltage at the nodes 105 and 108 are steady-state voltage signals while that at the node 104 it is AC signal; for instance, a triangular signal for cyclic voltammetry.
  • Electric potential at the first working electrode 102 with respect to reference electrode 100 is calculated by subtracting the voltage at the node 104 from the voltage at the node 108 (i.e. V108-V104).
  • the node 108 is grounded in the circuit.
  • Electric potential at the second working electrode 102 with respect to the reference electrode 100 is the same as the voltage at the nod 105.
  • This is enabled by installing the operational amplifier 113 as differential amplifier with R3, R4, R5, and R6 at the same resistance values (typically lOOkohmes).
  • Resistance values of Rl and R2 are selected based on the size of current signal at 102 and 103, with expected amplified signal from approximately 100 mV to 3V. Multiple resistors can be installed in parallel with a switch can be installed where Rl and R2 are located to enable selection of resistors with different values if necessary.
  • Bipotentiostat circuit shown in Figure 2A is used if two working electrodes with independent voltage control at each electrode 102, 103 are necessary for running an electrochemical testing. For instance, bipotentiostat circuit design is necessary for usage of rotating disk electrode (RDE) or interdigitated (IDA) electrode or any other electrode configuration that requires two working electrodes. If running a conventional three electrode electrochemical testing, potentiostat circuit design shown in Figure 2B or Figure 2C is suitable. A multiple working electrode with the same applied electric potential can be added by addition of i-v converter circuit consisting of operational amplifier 110, resistor Rl, node 103 as working electrode(s), 108 and 106.
  • a fully functional digital unit with a proper power source e.g. portable battery
  • a proper power source e.g. portable battery
  • the communication between the portable electronic device or a smartphone is done through a local wireless communication port 205 such as Bluetooth.
  • the host electronic device will control the portable detection device's electronic part through sending software commands via Bluetooth 205. Data acquired from the portable detection device will be transported through Bluetooth 205.
  • the wireless communication port 205 communicates with both smartphone device and the microcontroller 204 in the portable detection device.
  • the microcontroller 204 communicates with the smartphone 206 through wireless communication port 205 while controlling the input voltage 104, 105 of
  • DAC digital-to-analog converter
  • ADC analog-to-digital converter
  • An additional control unit 203 may be added if gain resistor value Rl or R2 needs to be selectable or any numeric control for fluidic control at the chip/glucose strip is necessary.
  • Fig. 10 shows a version of the device using a magnetic coil 405 instead of a Bluetooth module to transmit data to the smartphone. As the coil will is not configured to receive data from the smartphone, the device is configured to operate independently of input from the smartphone.
  • An alternative system is shown in Fig. 11 where both Bluetooth and a magnetic coil 405 are used.
  • the Bluetooth may be used to transmit instructions from the smartphone to the portable detection device, and could also be used as an additional means to transmit information from the portable detection device to the smartphone.
  • the output current can be graphed against the input voltage as shown in Figure 3A.
  • x-axis 300 is input voltage in volts (V) while y-axis 301 is output current typically in microamps ( ⁇ ) or nanoamps (nA). Peak current is characterized by measuring the difference between the point at which the output current is the highest 304 and the baseline signal 305.
  • Peak current can be used to calibrate the electrochemical signal, as shown in Figure 3B, with peak current in microampere in y-axis 311 and concentration of electrochemically active species (in this case, p-aminophenol is used) in millimoles in x-axis 310.
  • the portable detection device is to be operated with a smartphone application.
  • the process flow of the program is shown in Figure 4.
  • a user will collect sample fluid on the chip/glucose strip after inserting it in the strip holder 5.
  • data will be sent wirelessly to the mobile application; if not, it will alert the user to start a new test.
  • the data will be recorded and result will be displayed.
  • the user can record any related activity related to the test. If the data represents any abnormality in the sample content, it will automatically alert the user.
  • the mobile application will also log the data so that the user can access the data readily on the internet or provide access to data to interested parties such as the users physician in the case of diabetes monitoring.
  • the smartphone may be replaced by a handheld computing device such as a tablet PC, and lack a cellular network interface.
  • the portable computing device may include a WiFi port or other interface for connecting to the internet.
  • the computing device includes the local communication part, and processing capability of a personal computer and is attached to the detecting part.
  • the handheld computing device and corresponding detection device otherwise may be designed with the same characteristics as the smartphone and detection device described here.
  • the object for accessing the magnetic field value from smartphone magnetometer is triggered when the sensor value (i.e. magnetic field value) has changed (Hence the object name "onSensorChanged”). All the routines related to signal acquisition and processing are in this object, and these routines will also be triggered upon the changing the sensor value. This can make the coding tricky since the code is read from the top whenever the sensor value changes.
  • the speed at which the magnetic sensor values are uploaded can be set up, and it is set up to the fastest speed.
  • Initialize routine is set up init() to initialize all the variables and ArrayList needed to run the program.
  • ArrayList is one of the simplest data format used that can be used to record and manage a list of data. The routine is shown below:
  • Tlist new ArrayList ⁇ Long>()
  • deltaZ new ArrayList ⁇ Float>()
  • zflag triggers the signal processing routine.
  • Zpolar value indicates a significant increase (1) or decrease (-1) in dz value, and if there is no significant change in dz value, then zpolar value is set at 0.
  • dt value is not within the specified range, then the computer processes the first "tooth” as noise, and starts collecting zpolar data from scratch. If the first signal is successfully recognized as a "signal,” then the following routine is run:
  • int bitbit (int)(dt/tbit+0.5);
  • the routine above is the algorithm that reads the signal from magnetometer and registers "0" and "1" as true and false Boolean. It first recognizes the start and end signals by nested if statements, and calculates dt value for each tooth of the signal. Then, it calculates how many digits present within one tooth of the signal, and it records true or false, depending on the previous signal.
  • readsignalQ routine is called. This routine is run in order to register the signal packet into information - either status or data. For the status, the signal packet starts with "100,” and it should have 6 bits. For the data, the signal starts with "101,” and it has 14 bits.
  • readsignalQ routine reads the first three bits of the packet to determine whether the packet is status or data, and calls an appropriate routine (readstatusQ or readdataQ) to record the information.

Abstract

A portable detection device in a smartphone cover with magnetic wireless communication protocol is described. The electrochemical detection device consists of electrochemical detection unit (e.g., potentiostat), digital building block (microcontroller) and wireless communication port that can be connected with mobile devices such as smartphones. (e.g., USB, Bluetooth, NFC, or magnetic communication protocol described herein). The electrochemical detection unit can connect to a chip that contains electrodes and a port for receiving fluid for point-of-care diagnostic application, heavy metal detection, glucose monitoring, and water and food quality testing. Digital building block processes the signal received from the detection unit and sends the signal out via communication port. The electronic device is encapsulated within smartphone cover. The wireless communication port described herein allows the data to travel wirelessly from the device to a host mobile device (e.g., smartphone) within a very short distance using magnetic field as communication medium.

Description

PORTABLE DETECTION DEVICE
FIELD
[0001] Detection of electrochemically active species.
BACKGROUND
[0002] The inability to diagnose healthcare problems remotely and effectively has become a large focus of modern medicine. Currently the marketplace has a plethora of singular detection focused devices such as: glucose monitoring systems for diabetes patients, pregnancy testing strips, at home infectious disease detection including early cancer detection and human immunodeficiency virus (HIV) testing, drug toxicity testing and heavy metal detection for environmental safety.
[0003] However such detection kits, although made to be stand-alone hand-held devices, can be limited in their effectiveness due to their difficulty of use for the end-user or patient. For instance, glucose sensors for diabetes patients need to be used at least three times a day, but the regular testing for glucose monitoring can be difficult depending on the lifestyle of the patient; therefore an enhanced user experience with each test taken can contribute to an overall increased quality of life for the user.
[0004] Currently, there exist a large number of portable digital communication devices such as smartphones, tablets, e-book readers and digital music players and these multifunctional electronic platforms enable consumers to have a phone, audio/music player, global positioning system (GPS), camera, wireless communication device, and many other electronic functionality in a single standalone device. The most effective way to solve diagnostic healthcare problems, in terms of cost and efficiency, is to utilize the already large distribution and penetration of digital communication devices in everyday lives of patients to distribute a portable diagnostic platform.
[0005] US patent applications 2012/0130646 to Landis and 2010/0000862 to Rao disclose detection kits that work in combination with cell phones. However, the detection system of Rao connects to the end of the cell phone and thus extends the length of the cell phone, which may be inconvenient, and the system of Landis is not directly connected to the cell phone and thus must thus be carried separately. The systems of Landis and Rao use conventional wireless communication such as Bluetooth or a wired connection. [0006] In many portable, mobile, wearable devices, communication between the master and slave devices are essential for data management. For example, a medical device can be made into a handheld size if the core functionality of the medical devices is kept as succinct as possible while eliminating other generic features of hardware (e.g. display, data storage, data analysis etc.), as long as the device (or a module) can communicate the critical information to the master device (e.g. computers, smartphones, tablet PC).
[0007] Many communication protocols exist to facilitate the communication between these devices, and they can be largely categorized into two major types - communication protocols using wires, and wireless communication protocols. Examples of wired communication protocols include universal serial bus (USB) and audio jack. These communication protocols require a wire to be connected between the master and slave device. Depending on the type of the communication protocol, both the devices require a program that is configured to transmit and receive the specific type of data coming from a communication protocol. Also, a user needs to plug in a wire (e.g. USB cable or audio jack) into the devices. If at least one of the devices have plugs that are not compatible with the wire, then either the wire or connector need to be redesigned to fit into the existing devices.
[0008] Wireless communication protocol such as Bluetooth, Zigbee, or Wi-fi does not require wires, and therefore considered as more convenient for users. However, it still needs a specific configuration that can transmit and receive the data communicated in each protocol. The long distance that these communication protocol travels is potentially dangerous because the communication can be interrupted or hacked by an external device that are configured to receive and transmit information without authorization. Synchronization process for these protocols is required for the communication between two devices to occur, and this could add another complication for users to use wireless communication protocols.
[0009] It is also known to use near-field magnetic induction as a communication method. Conventional near-field magnetic induction uses resonance between two coils, one in each device between which the communication occurs. The need to have such hardware in both devices makes it unsuitable for communication with an off-the-shelf consumer product.
SUMMARY
[0010] In an embodiment, there is provided a communication system for communicating between a slave device and a master device, the master device having a non-coil magnetic sensor and having a microprocessor programmable to process input from the magnetic sensor, the communication system comprising a magnetic coil in the slave device for generating a magnetic field, and a controller in the slave device configured to control the magnetic coil to modulate the magnetic field to represent data to be transmitted to the master device, the modulation of the magnetic field being detectable by the magnetic sensor when the slave device is located in proximity to the master device. In various embodiments, the magnetic coil may modulate the magnetic field by turning on and off, the magnetic coil may modulate the magnetic field by emitting positive, negative, and 0 magnetic field, there may be plural magnetic coils in the slave device oriented to produce respective magnetic fields in different directions, the magnetic sensor being able to distinguish modulation of the magnetic field in the different directions, data may be represented using the magnitude of the magnetic field, and data may be represented using a time difference in "on" mode and "off mode.
[0011] In another embodiment, there is provided a portable detection device for
communicating with a smartphone having a network communication part and a magnetic sensor, the portable detection device comprising: a communication system as described in any of the above embodiments, a detection part adapted for generating an electrical signal upon detecting an electrochemically active species, and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part. In various embodiments, the portable detection device may be embedded in a cover for the smartphone, the detection part may comprise an electrochemical cell having electrodes and a potentiostat circuit for supplying stable voltage input at the electrodes, the portable detection device may have a digital to analog converter for converting a digital signal from the microcontroller to an analog signal applied to the electrodes, the portable detection device may have a current to voltage converter followed by analog to digital converter for converting current appearing at the electrodes to a digital signal to be processed at the microcontroller, the smartphone may have a local communication part and the portable detection device may have a
communication part for communicating with the local communication part, and the local communication part may comprises a Bluetooth wireless communication port, the detection part may comprise interdigitated electrodes and a bipotentiostat circuit, the detection part may comprises a rotating disk electrode and bipotentiostat circuit, the detection part may incorporate a microfluidic chip, and the microfluidic chip may comprise one or more of a glucose strip and immunoassay chip, the detection part may incorporate a microfluidic chip holder, the portable detection device may have an installed power source, the portable detection device may have a lancer attached to the portable detection device, the portable detection device may have a chip pocket attached to or forming part of the portable detection device.
[0012] In another embodiment, there is provided a portable detection device for
communicating with a handheld computing device having a magnetic sensor, the portable detection device comprising a communication system as described in any of the embodiments described in the first paragraph of this summary, a detection part adapted for generating an electrical signal upon detecting an electrochemically active species, and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part.
[0013] In another embodiment, there is provided a portable detection device for
communicating with a smartphone having a network communication part and a local communication part, the portable detection device comprising a communication part adapted for wireless communicating with the local communication part; a detection part adapted for generating an electrical signal upon detecting an electrochemically active species; and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication part and the detection part.
[0014] In various embodiments, the portable detection device may be embedded in a cover for the smartphone, and may incorporate various types of electrochemical cells, microfluidic chips, various types of potentiostats, converters, various types of electrodes, and an installed power source.
[0015] In another embodiment, a portable detection device is provided for communicating with a handheld computing device having a local communication part.
[0016] In another embodiment, a smartphone is configured to control the portable detection device. A method of detecting an electrochemically active species comprising operating a smartphone to control the portable detection device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] There will now be described exemplary embodiments of a portable detection device, with references to the figures by way of example, in which: [0018] Figure lAto IF illustrates a smartphone cover embedded with an electrochemical detection circuit with a chip holder.
[0019] Figure 2Ato 2D illustrates exemplary (bi)potentiostat schematics embedded in the smartphone cover.
[0020] Figure 2E illustrates a flow diagram of how the electrochemical detection system circuit works.
[0021] Figure 3A illustrates an exemplary result of cyclic voltammetry curve (and calibration curve) that can be obtained from the device.
[0022] Figure 3B illustrates an exemplary result of a calibration curve to determine correlation between electronic peak signal from CV and concentration of an electrochemical active specie (pAP is used in this example).
[0023] Figure 4 illustrates an exemplary flow diagram for smartphone application software, (how the data is collected, processed, and managed from the electrochemical detection system to a smartphone device).
[0024] Figure 5 is a graph showing an example magnetic field produced by a coil near a smartphone as detected at a magnetic field sensor of the smartphone.
[0025] Figure 6 is a graph showing an example magnetic field and an example threshold for threshold-based signal processing.
[0026] Figure 7 is a graph of signal value resulting from processing based on the threshold in Figure 6.
[0027] Figure 8 is a graph showing an example of changes in a magnetic field and positive and negative thresholds for magnetic field changes.
[0028] Figure 9 is a graph of signal value resulting from processing changes in the magnetic field strength according to thresholds in Figure 8.
[0029] Figure 10 is a diagram showing an electrochemical detection circuit using a magnetic coil to communicate to a smartphone.
[0030] Figure 11 is a diagram showing an electrochemical detection circuit using a magnetic coil and a conventional communication system such as Bluetooth to communicate with a smartphone. DETAILED DESCRIPTION
[0031] Magnetic communication enables one-way (typically from slave to master) wireless communication over a distance of a few centimeters (max -lOcm) as long as the slave device has inductive coil as a transmitter and the master device with embedded magnetic sensor(s). This type of communication is especially useful in setting up a wireless communication protocol between mobile devices such as smartphones and tablet PCs and an attached hardware accessory. Magnetic communication travels over a short distance because the magnitude of magnetic field decreases significantly. The possibility of hacking the signal is limited by the distance that the communication can travel. In order for someone to hack into the signal, the hacking device need to be physically placed on top of the slave device (with distance less than 10 cm), which emits the signal.
[0032] Another advantage of the communication is in its simplicity in implementation on existing mobile device operation system (OS) platforms. For example, Google Android provides an open source algorithm that monitors the magnetic field over a period of time. By monitoring the magnetic sensor, one can easily implement a magnetic communication protocol on Android application. For the transmitting magnetic signal, one can program a microcontroller to turn the signal on and off (in unidirectional or bidirectional) the magnetic coil. The method could also be implemented on other OSs such as iOS, BlackBerry OS, and Microsoft Windows.
[0033] Magnetic sensor overview
[0034] In smartphones, there are different types of micro-sized sensors that enable smartphones to measure different things around it. Example sensors include accelerometer, temperature sensors, gravity sensors, gyroscope, light sensors, accelerometer, magnetometer, pressure sensor, proximity sensor, relative humidity sensors, rotations vector sensors. These sensors are beneficial for making efficient and effective smartphone applications in many different areas such as GPS, compass, digital bubble level, temperature and humidity monitor, smartphone games using accelerometers and others.
[0035] Magnetic sensors used in consumer devices such as smartphones include Hall effect, giant magnetoresistance, magnetic tunneling junction, anisotropic magnetoresistance, and Lorentz force sensors. The term "magnetic sensor" used in this document may include plural magnetic sensors, for example plural magnetic sensors used to detect magnetic fields in different directions. Plural coils can be used to generate magnetic fields in different directions. In principle, the magnetic fields in the different directions can be separately detected by the magnetic sensor allowing more bandwidth.
[0036] Preliminary Testing - monitoring magnetic sensor positions while transmitting signal from an inductor
[0037] In order to do feasibility testing, the magnetic field and the time is recorded in ArrayList<Float> and ArrayList<Long>, and when the button is pushed, the program would spit out the array consists of magnetic field in all directions as well as its time. The source code is provided in Appendix A.
[0038] In a testing arrangement, a copper coil from a hard disk drive is used to drive an electromagnetic field from an electronic signal generated by the device. When the voltage is applied across the coil, then the current produced from the potential will cause the magnetic field to appear. If the voltage is off, then there will be no magnetic field from the coil. The copper coil is placed directly underneath the smartphone. In this specific testing arrangement, a Nexus 4 smartphone was used.
[0039] Using one I/O pin directly from the CPU, it was possible to pulse out a magnetic field over a period of time, as shown in Figure 5. Digitized signal is clearly distinguished from the graph, indicating the magnetic field can indeed be used as local wireless communication tool.
[0040] Because the coil is small and the circuit is not optimized for magnetic communication, the signal is still weak; therefore, positioning the coil directly under where the magnetometer in the smartphone was important. Otherwise, the magnetic field is not strong enough to display digitized magnetic signal from the magnetometer.
[0041] Magnetic communication is slower than other types of high frequency communication methods such as Wi-Fi and Bluetooth. As shown in the graph, each signal has a finite slope, and it takes time for the magnetometer to recognize the change in surrounding magnetic field.
[0042] Methods to recognize and read the signal
[0043] 1) Basic - work with the raw data, recognize the signal by setting threshold magnitude and threshold dt
[0044] Take the raw signal, and set a threshold magnetic field value. If the signal is above the threshold value, register 1. If not, then register 0. After digitizing the signal, calculate delta t of each tooth of the signal to determine how many Is and 0s exist within each tooth. [0045] An example is shown in the graphs of Figure 6 and Figure 7. In the raw signal data, by looking at the raw signal, we determine the reasonable threshold value is 10 μΤ. If the raw signal is above 10 μΤ, then signal value of 1 is registered; otherwise, signal value of 0 is registered. The result of processing the raw signal shown in Figure 6 is shown in Figure 7.
[0046] Strengths: This method is the simplest signal processing, and it will require the least computing effort
[0047] Weakness: The magnetic field value depends on where the smartphone is placed and where it is located and directed, since the earth magnetic field as well as surrounding magnetic field (if exists) will affect the magnetic field signal. Therefore, in order for this signal processing technique to work, the threshold value needs to be changed every time the program is turned on.
[0048] 2) Delta of magnetic signal
[0049] Instead of taking the raw data directly for signal processing, the change in magnetic field value (comparing the current magnetic field value and the past value) is used to recognize and evaluate the signal, as shown in Figures 8 and 9.
[0050] Depending on the magnitude of change in magnetic field (ΔΜ), an arbitrary value of - 1, 0, 1 are assigned. If ΔΜ was a large negative number, it means that the magnetic field is decreasing. If ΔΜ was a large positive number, it means that the magnetic field is increasing. The flat positive or negative line on ΔΜ graph indicates the slope of magnetic field graph, and it tells the start and the end of the magnetic field signal tooth. The width of the signal (i.e. At or dt) is determined by measuring dt value from the starting point of ΔΜ negative tooth to the starting point of ΔΜ positive tooth, and vice versa (Figure 9 shows the result of processing the signal shown in Figure 8).
[0051] Strengths: Change in magnetic signal compares the current magnetic field value to the past magnetic field; therefore, no matter what the starting magnetic field value is, we will always detect the change in magnetic field due to the signal from the external magnetic coil.
[0052] Weakness: Because this method is highly dependent on the threshold of change in magnetic field and the time gap between each threshold, it will result in some error and breakage in signal processing if the actual signal is weaker than the anticipated signal. Also, it does not compensate the change in magnetic field during signal processing operation; in other words, if the user moves the smartphone around when the signal is being transferred, the data may not be transferred properly. [0053] 3) AM (Amplitude Modulation) & FM (Frequency Modulation)
[0054] strengths: Because AM or FM signals involve high frequency, it is able to deliver the signal with more accuracy and less noise than the previous two methods.
[0055] Weakness: We do not know whether the open source Android platform allows us to get the true raw data of the magnetic field value. It is likely that the raw magnetic field value obtained from the program is already filtered, and if high frequency signal is filtered through low pass filter, then AM signal may not be registered.
[0056] 4) Fourier Transform - This can also deliver the signal with lots of ambient noise around it, but it is complicated to set up algorithm in software.
[0057] 5) Other signal processing techniques that is not discussed in this report may also be available, but they are not considered.
[0058] In a preferred embodiment the communication method used is #2 (delta of magnetic signal). Although it will be ideal to utilize complex signal processing techniques such as AM, FM, FFT or others to maximize the accuracy, the method #2 is simpler to execute, and it has reasonable amount of accuracy.
[0059] A modified fusion sensor algorithm could be used to compensate the distortion of magnetic field by the movement of smartphone and smartphone case.
[0060] The magnetic coil communication system can be used, for example, in a portable detection device to communicate with a smartphone as an alternative to or in conjunction with a conventional communication system such as Bluetooth.
[0061] A purpose of the portable detection device is to utilize mobile phone technology to simplify monitoring needs of everyday individuals. By using a mobile phone's processing power instead of an on-board processing system with developed graphic user interface (GUI), the device is able to act as an integrated accessory dependent on its "master" mobile device. Development of a mobile application to link the accessory to the mobile device's processor is done via Bluetooth communication.
[0062] The digital communication processing device encapsulating protective cover is advantageous to currently available monitoring systems for several reasons: cost, user experience and convenience. [0063] Since the device is to be manufactured without significant on-board processing power the device will be significantly less expensive to manufacture, therefore the cost savings can be passed on to the consumer.
[0064] In an embodiment, a monitor is embedded in a mobile device protective cover and therefore it serves a dual purpose of both protecting a customer's mobile device from damage as well as enabling on-the-go monitoring. This dual purpose allows customers to forgo the worry of bringing two devices to their workspace or daily destinations as both a monitor and mobile communication device are now together in one package. For example, diabetics would be able to forgo carrying their required blood sugar monitor with them to their workspace as well as their mobile communication device, due to the two systems being integrated into one unit through the use of this portable detection device.
[0065] In an embodiment, a smartphone cover embedded with an electrochemical detection system is described. The device comprises in an embodiment two main parts: smartphone cover and an embedded electrochemical detection circuit. The smartphone cover provides cosmetic and shock protection for the encased digital communication device while also integrating a detection system onto any digital communication processor device. A designed detection circuit has components necessary to perform electrochemical analysis, which analyzes chemical component of a liquid sample in the form of an electronic signal. A potentiostat circuit is included in the system for supplying stable voltage input at electrodes of electrochemical cell. The electric potential between reference electrode and working electrode is applied through digital to analog converter (DAC), which converts digital signal from microcontroller to analog signal. The current at working electrode(s) are measured by current to voltage (i-V) converter followed by analog to digital converter (ADC). When the analog signal is converted to digital signal, that signal is recorded to microcontroller, and the set of data is sent out through wireless communication port (Bluetooth) to a smartphone device, or a magnetic communication system as detailed above. The system is to be further developed to control a sample liquid using electronic signal.
[0066] For conventional electrochemical experiments, a potentiostat with three electrodes (reference, counter, and working electrode) is sufficient. However, when running ultrasensitive electrochemical detection experiments with interdigitated (IDA) electrodes, a bipotentiostat circuit is necessary to run independent voltage control at two working electrodes. [0067] When electrochemically active species in liquid sample comes into contact with the electrodes upon a certain electric potential, they undergo oxidation and reduction (redox) reaction. During this stage, electrons are transported from the molecule undergoing the redox reaction. This electrochemical reaction can be described by mass transport phenomenon. The more electrochemically active species present in sample, the more electronic signal is generated. The electrochemically active species include, but are not limited to: hydrogen peroxide, ferrocene, ferricyanide, p-aminophenol (pAP), p-nitrophenol (pNP),
tetramethylbenzidine (TMB), metal ions. The IDA electrode and bipotentiostat can be used to increase sensitivity of signal significantly only if the specie can undergo redox recycling or in other words the redox species reaction is reversible.
[0068] Virtually any type of microfluidic chip can be inserted into the circuit such as glucose strips, immunoassay lab-on-a-chip devices, and white papers. For glucose sensing, glucose strips are required to monitor glucose level. The strips consist of electrode for
electrochemical detection, glucose oxidase enzyme for generation of hydrogen peroxide from blood glucose, and a micro-channel for liquid handling. For analytes (biomolecules, hormones, proteins, DNAs, cells, etc.) detection, microfluidic immunoassay chips can be utilized. The chips consist of a microfluidic circuit with microfluidic valves for automatic liquid handling if liquid handling is necessary, immunoassay reagents, and electrodes. For heavy metal detection anodic stripping voltammetry should be run on the electrodes while liquid sample is in contact with the electrodes since it is not necessary to have a confined microfluidic channel for liquid handling, as the heavy metal in sample will used directly as the electrochemically active species, unless the heavy metal is selectively captured by antibody or proteins. If concept of selective capturing of proteins is used, then microfluidic circuit with automatic liquid handling can be necessary.
[0069] An advantage of this portable detection device is that it simplifies the integration of portable electronic devices such as smartphone devices and electrochemical detection system for applications such as glucose monitoring, analyte monitoring, or heavy metal detection. This portable detection device allows consumers to use their smartphones or other portable digital communication device as glucose sensors, point-of-care diagnostic device, heavy metal monitoring device at the point of required detection. This is done for example through simple wireless communication module (for example, Bluetooth) between smartphone and the electrochemical detection circuit. It also provides the simplest solution to integrate an electronic device with an existing smartphone as a simple smartphone accessory. The smart phone comprises both processing capability and two wireless communication parts. One wireless communication part is for communication with a mobile phone network and the other communication part is for local communications, for example Bluetooth. Such devices are ubiquitous. Alternatively other systems can be used for local communication such as the magnetic system detailed above.
[0070] The below are applications of the device being used as a cellphone case:
[0071] Pollen/airborne allergy detection
[0072] Bio-warfare agent detection
[0073] Monitoring of blood borne antigens, constituents (such as lactic acid for exercise, blood sugar levels for diabetic monitoring)
[0074] Monitoring sweat, sputum, urine, breath
[0075] Infectious disease detection
[0076] Heavy metal monitoring in water/environmental monitoring
[0077] Description on how to put smartphone covers on smartphones; different designs for cover/case for other portable electronic device (tablets) will be available
[0078] In the first embodiment of the portable detection device, as shown in Figure lA to IF, a case for a portable electronic device with embedded electrochemical detection circuit is provided. Figure lA is the front view, Figure IB is the back view, Figure 1C is the top view, Figure ID is the bottom view, Figure IE is the right view, and Figure IF is the left view. The portable detection device is comprised of a lip 1 that will hold the portable electronic device (e.g. smartphones) and the main body 2 together, and may include a window 3 A for allowing a camera to function while the case is in place on the smartphone. Various other methods may be used to secure the portable detection device on the portable electronic device. The portable detection device also includes a "bump" 4 with a chip/glucose strip holder 5 that will work as an electrochemical detection device. The main advantage of implementing the portable detection device with a portable electronic device such as smartphones is that it provides an added capability to analyze and quantify an analyte of interest in a sample fluid dropped on a chip or glucose strip that will be connected at the chip holder 5. A portable chip pocket 6 and a lancer 3 can also be attached to or form part of the portable detection device to ease carrying apparatus required for point-of-care health monitoring. The chip pocket 6 will house biochips such as glucose strips, microfluidics, or white papers that are capable of measuring and detecting chemical specie in sample fluid when connected to the chip/glucose holder 5. The customer will put in several glucose strips or any other detection chips to the chip pocket 6, and they will be able to monitor their health anywhere, anytime, as long as they carry their smartphones with the invention attached. The lancer 3 can be used for piercing a finger or other human body parts to obtain a drop of blood.
[0079] Description of potentiostat circuits
[0080] Within the embodiment 4, (bi)potentiostat device is included in order to enable portable electrochemical detection, (power is to be provided with a conventional battery such as lithium battery, and the bump 4 will have its own cover so that a user can replace the battery when the battery is drained.) Potentiostat device consists of up to four electrodes: reference electrode 100, counter electrode 101, first working electrode 102, and second working electrode 103. Voltage at reference electrode 100 and counter electrode 101 is controlled by operational amplifier 111. When an electrochemical cell is connected, the operational amplifier 111 acts as a voltage follower, and the voltages at nodes 100 and 101 will be the same value as the voltage at node 104, regardless of what is happening within the electrochemical cell. In some cases, an additional voltage follower 114 can be added to minimize the current flow at reference electrode 100 as shown in Figure 2D. Input voltage 104, 105, 108 for voltammetry testing is sent from the microcontroller as an analog signal through analog-to-digital (ADC) signal conversion. Normally, voltage at the nodes 105 and 108 are steady-state voltage signals while that at the node 104 it is AC signal; for instance, a triangular signal for cyclic voltammetry. Electric potential at the first working electrode 102 with respect to reference electrode 100 is calculated by subtracting the voltage at the node 104 from the voltage at the node 108 (i.e. V108-V104). Typically, the node 108 is grounded in the circuit. Electric potential at the second working electrode 102 with respect to the reference electrode 100 is the same as the voltage at the nod 105. This is enabled by installing the operational amplifier 113 as differential amplifier with R3, R4, R5, and R6 at the same resistance values (typically lOOkohmes). As an output signal, current is generated at each working electrode 102, 103, and they are amplified using an active current to voltage converter circuit with operational amplifiers 112 and 113. Resulting output signal is voltage at 106 for the current at working electrode 103 with V=i(103)*Rl, and voltage at 107 for the current at working electrode 102 with V=i(102)*R2. Resistance values of Rl and R2 are selected based on the size of current signal at 102 and 103, with expected amplified signal from approximately 100 mV to 3V. Multiple resistors can be installed in parallel with a switch can be installed where Rl and R2 are located to enable selection of resistors with different values if necessary.
[0081] Different designs of (bi)potentiostat can be used depending on the applications. Bipotentiostat circuit shown in Figure 2A is used if two working electrodes with independent voltage control at each electrode 102, 103 are necessary for running an electrochemical testing. For instance, bipotentiostat circuit design is necessary for usage of rotating disk electrode (RDE) or interdigitated (IDA) electrode or any other electrode configuration that requires two working electrodes. If running a conventional three electrode electrochemical testing, potentiostat circuit design shown in Figure 2B or Figure 2C is suitable. A multiple working electrode with the same applied electric potential can be added by addition of i-v converter circuit consisting of operational amplifier 110, resistor Rl, node 103 as working electrode(s), 108 and 106. It is possible to control voltage at the node 108 to control the electric potential at each individual working electrodes with respect to the reference electrode 100; however, one needs to add an additional functional block to control the input voltage at the node 108. A simpler potentiostat design is also shown in Figure 2D. Unlike the other designs, this particular design does not have separate working electrode and counter electrode, and only has two electrodes: counter electrode 100/101 and a working electrode 103. This design is simpler than the other ones; however, in reference to its desired application the operator needs to consider whether there will be significant electric current influencing the input voltage at the node 104 during the electrochemical detection test.
[0082] Detailed description of electrochemical detection system and flow diagram
[0083] Along with a (bi)potentiostat shown in Figure 2A to 2D, a fully functional digital unit with a proper power source (e.g. portable battery) needs to be installed in order to run the device, as shown in Figure 2E. The communication between the portable electronic device or a smartphone is done through a local wireless communication port 205 such as Bluetooth. The host electronic device will control the portable detection device's electronic part through sending software commands via Bluetooth 205. Data acquired from the portable detection device will be transported through Bluetooth 205. The wireless communication port 205 communicates with both smartphone device and the microcontroller 204 in the portable detection device. The microcontroller 204 communicates with the smartphone 206 through wireless communication port 205 while controlling the input voltage 104, 105 of
(bi)potentiostat 200 through digital-to-analog converter (DAC) 201. The output voltage is sent back to microcontroller through analog-to-digital converter (ADC) 202. An additional control unit 203 may be added if gain resistor value Rl or R2 needs to be selectable or any numeric control for fluidic control at the chip/glucose strip is necessary.
[0084] Fig. 10 shows a version of the device using a magnetic coil 405 instead of a Bluetooth module to transmit data to the smartphone. As the coil will is not configured to receive data from the smartphone, the device is configured to operate independently of input from the smartphone. An alternative system is shown in Fig. 11 where both Bluetooth and a magnetic coil 405 are used. The Bluetooth may be used to transmit instructions from the smartphone to the portable detection device, and could also be used as an additional means to transmit information from the portable detection device to the smartphone.
[0085] Interpretation of electrochemistry data received from electronic circuit
[0086] When the raw data from the node 106 or 107 is recorded through the digital unit through cyclic voltammetry, the output current can be graphed against the input voltage as shown in Figure 3A. In case of cyclic voltammetry characterization, x-axis 300 is input voltage in volts (V) while y-axis 301 is output current typically in microamps (μΑ) or nanoamps (nA). Peak current is characterized by measuring the difference between the point at which the output current is the highest 304 and the baseline signal 305. Peak current can be used to calibrate the electrochemical signal, as shown in Figure 3B, with peak current in microampere in y-axis 311 and concentration of electrochemically active species (in this case, p-aminophenol is used) in millimoles in x-axis 310.
[0087] Description on how to operate the system using a smartphone application as shown in Figure 4
[0088] The portable detection device is to be operated with a smartphone application. The process flow of the program is shown in Figure 4. First, a user will collect sample fluid on the chip/glucose strip after inserting it in the strip holder 5. Then, if the test is successfully run, data will be sent wirelessly to the mobile application; if not, it will alert the user to start a new test. When the data is sent, the data will be recorded and result will be displayed. The user can record any related activity related to the test. If the data represents any abnormality in the sample content, it will automatically alert the user. The mobile application will also log the data so that the user can access the data readily on the internet or provide access to data to interested parties such as the users physician in the case of diabetes monitoring.
[0089] Description on how the system operates for different applications (if necessary) [0090] Beyond the purpose of diabetic's blood monitoring, there are many other reasons to enable integration of a monitor into a mobile communication such as: Cortisol level monitoring for stress, lactic acid monitoring for exercise exhaustion, and environmental testing such as in air pollen detection for allergies as well water purity testing for heavy metal contamination.
[0091] In some embodiments, the smartphone may be replaced by a handheld computing device such as a tablet PC, and lack a cellular network interface. The portable computing device may include a WiFi port or other interface for connecting to the internet. In this instance, the computing device includes the local communication part, and processing capability of a personal computer and is attached to the detecting part. The handheld computing device and corresponding detection device otherwise may be designed with the same characteristics as the smartphone and detection device described here.
[0092] Immaterial modifications may be made to the embodiments described here without departing from what is covered by the claims.
[0093] In the claims, the word "comprising" is used in its inclusive sense and does not exclude other elements being present. The indefinite articles "a" and "an" before a claim feature do not exclude more than one of the feature being present. Each one of the individual features described here may be used in one or more embodiments and is not, by virtue only of being described here, to be construed as essential to all embodiments as defined by the claims.
APPENDIX A
The object for accessing the magnetic field value from smartphone magnetometer is triggered when the sensor value (i.e. magnetic field value) has changed (Hence the object name "onSensorChanged"). All the routines related to signal acquisition and processing are in this object, and these routines will also be triggered upon the changing the sensor value. This can make the coding tricky since the code is read from the top whenever the sensor value changes. The speed at which the magnetic sensor values are uploaded can be set up, and it is set up to the fastest speed.
In this development stage, only the magnetic field in z-direction is used, since z directional magnetic field is affected by the electromagnet underneath the smartphone (for the reference in axis of a smartphone, look up Sensor page in Android development). In future, this may be changed so that the algorithm monitors magnetic field in all directions. Initialize routine is set up init() to initialize all the variables and ArrayList needed to run the program.
First, the time, z magnetic field, and change in z magnetic field (dz) are monitored and recorded in ArrayList. ArrayList is one of the simplest data format used that can be used to record and manage a list of data. The routine is shown below:
t = System.currentTimeMillisQ - ttime;
z = sensorEvent. values [2J;
Zlist.add(z);
Tlist.add(t);
if (Zlist.sizeQ < 2) {
dz = 0;
deltaZ. add(dz);
}
else {
int Zsize = Zlist.sizeQ;
dz = Zlist.get(Zsize-l)-Zlist.get(Zsize-2);
deltaZ. add(dz);
For the first dz value, since there is only one z, we cannot compare this initial z value to any value; therefore, the corresponding dz is set at 0. Other dz values (from the second one and on) were obtained by subtracting the previous z value from the current z value. Here, the time gap is not taken into an account. Start of a new signal packet is recognized by the magnitude of dz. When the program checks dz value and if dz value is above threshold value, then it triggers a flag (called zflag, and this algorithm puts zflag at 1), and the flag calls a routine to process the signal. The start signal recognition and flag routine is shown below:
if (dz > dzthreshold) {
zflag = 1;
I
if(zflag != l) {
Zlist = new ArrayList<Float>();
Tlist = new ArrayList<Long>();
deltaZ = new ArrayList<Float>();
}
When the start of the signal is recognized, then zflag triggers the signal processing routine. First, zpolar values are assigned for each dz value. Zpolar value indicates a significant increase (1) or decrease (-1) in dz value, and if there is no significant change in dz value, then zpolar value is set at 0. Then, time difference (dt) of each tooth of the signal is calculated by taking the absolute difference between the time at which either 1 or -1 starts and the time at which the next 1 or -1 starts. For instance, if zpolar value changes from 0 to 1 at t = 100, changes back to 0 at t=150, and changes to -1 at t = 200, the dt of the signal would be dt = 200 - 100 = 100. For the first set of zpolar values, it first checks whether dt value of the first signal is sufficient enough:
if (zflag == 1) {
Zpolar. add(polarity(dz));
if (Zpolar.sizeQ == 1) {
tinitial = tfinal;
tfinal = t;
dt = tfmal-tinitial;
if ((dt > = tbit-2.8*tbitpercent) && (dt < = tbit+2.8*tbitpercent))
ZSignal. add(rue);
}
else { Zpolar = new ArrayList<Integer>();
zflag = 0;
I
I
If dt value is not within the specified range, then the computer processes the first "tooth" as noise, and starts collecting zpolar data from scratch. If the first signal is successfully recognized as a "signal," then the following routine is run:
if (Zpolar. size () >= 2) {
if (polarity (dz) !=0) { //check if zpolar is 0
if (Zpolar. get (Zpolar. size()-l) -Zpolar. get (Zpolar. sizeQ -2) ! = 0) {
tinitial = tflnal;
tflnal = t;
dt = tflnal - tinitial;
//end calculating delta t of a signal
//bitbit refers to the number of bits included within one signal
int bitbit = (int)(dt/tbit+0.5);
if ((dt >= bitbit*tbit-tbitpercent) && (dt <= bitbit*tbit+tbitpercent)) {
ZSignal. add(!ZSignal. get(ZSignal. size()-l));
or (int ii = 1; ii < bitbit; {
ZSignal. add(ZSignal.get(ZSignal. size()-l));
}}}}};
The routine above is the algorithm that reads the signal from magnetometer and registers "0" and "1" as true and false Boolean. It first recognizes the start and end signals by nested if statements, and calculates dt value for each tooth of the signal. Then, it calculates how many digits present within one tooth of the signal, and it records true or false, depending on the previous signal.
Any signal packet always starts with "1" and "0," and the first signal is assumed to be "1" (recorded as "true"). Then, the second signal is recognized, and since the first signal is "true," the program automatically records "false" which is a different signal from the first signal. Final routine checks if the signal packet is valid; if a valid signal packet is not arrived within 2 seconds (2000 ms) since the first signal was registered, then it considers that the signal is noise, and starts receiving the signal from scratch. Because any signal packet ends with "1," this recognition tool works.
Figure imgf000021_0001
if(ZSignal.size() > = 2 && ZSignal.sizeQ == 6 && signaltypeQ == SIGNAL STATUS) { readsignalQ;
initQ;
}
else if (ZSignal.sizeQ > = 2 && ZSignal.sizeQ == 14 && signaltypeQ == SIGNAL DATA) { readsignalQ;
initQ;
}
else {
initQ;
II;
In this routine, readsignalQ routine is called. This routine is run in order to register the signal packet into information - either status or data. For the status, the signal packet starts with "100," and it should have 6 bits. For the data, the signal starts with "101," and it has 14 bits. readsignalQ routine reads the first three bits of the packet to determine whether the packet is status or data, and calls an appropriate routine (readstatusQ or readdataQ) to record the information.

Claims

1 A communication system for communicating between a slave device and a master device, the master device having a non-coil magnetic sensor and having a microprocessor programmable to process input from the magnetic sensor, the communication system comprising: a magnetic coil in the slave device for generating a magnetic field; and a controller in the slave device configured to control the magnetic coil to modulate the magnetic field to represent data to be transmitted to the master device, the modulation of the magnetic field being detectable by the magnetic sensor when the slave device is located in proximity to the master device.
2. The communication system of claim 1 in which the magnetic coil modulates the magnetic field by turning on and off.
3. The communication system of claim 1 in which the magnetic coil modulates the magnetic field by emitting positive, negative, and 0 magnetic field.
4. The communication system of claim 1 comprising plural magnetic coils in the slave device oriented to produce respective magnetic fields in different directions, the magnetic sensor being able to distinguish modulation of the magnetic field in the different directions.
5. The communication system of claim 1 in which data is represented using the magnitude of the magnetic field.
6. The communication system of claim 2 in which data is represented using the time difference in "on" mode and "off mode.
7. A portable detection device for communicating with a smartphone having a network communication part and a magnetic sensor, the portable detection device comprising: a communication system as claimed in any one of claims 1-6; a detection part adapted for generating an electrical signal upon detecting an electrochemically active species; and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part.
8. The portable detection device of claim 7 embedded in a cover for the smartphone.
9. The portable detection device of claim 7 or 8 in which the detection part comprises an electrochemical cell having electrodes and a potentiostat circuit for supplying stable voltage input at the electrodes.
10. The portable detection device of any one of claims 7-9 further comprising a digital to analog converter for converting a digital signal from the microcontroller to an analog signal applied to the electrodes.
11. The portable detection device of any one of claims 7-10 further comprising a current to voltage converter followed by analog to digital converter for converting current appearing at the electrodes to a digital signal to be processed at the microcontroller.
12. The portable detection device of any one of claim 7-11 in which the smartphone also has a local communication part and the portable detection device further comprises a communication part for communicating with the local communication part.
13. The portable detection device of claim 12 in which the local communication part comprises Bluetooth wireless communication port.
14. The portable detection device of claim 7 in which the detection part comprises interdigitated electrodes and a bipotentiostat circuit.
15. The portable detection device of claim 7 in which the detection part comprises a rotating disk electrode and bipotentiostat circuit.
16. The portable detection device of any one of claims 7-15 in which the detection part incorporates a microfluidic chip.
17. The portable detection device of claim 16 in which the microfluidic chip comprises one or more of a glucose strip and immunoassay chip.
18. The portable detection device of any one of claims 7-15 in which the detection part incorporates a microfluidic chip holder.
19. The portable detection device of any one of claims 7-18 further comprising an installed power source.
20. The portable detection device of any one of claims 7-19 further comprising a lancer attached to the portable detection device.
21. The portable detection device of any one of claims 7-20 further comprising a chip pocket attached to or forming part of the portable detection device.
22. A portable detection device for communicating with a handheld computing device having a magnetic sensor, the portable detection device comprising: a communication system as claimed in any one of claims 1 -6; a detection part adapted for generating an electrical signal upon detecting an electrochemically active species; and a microcontroller provided in communication with the detection part and the communication part, the microcontroller being adapted for controlling the communication system and the detection part.
PCT/CA2016/050385 2015-04-02 2016-04-01 Portable detection device WO2016154762A1 (en)

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