Impedance Plethysmograph Design

Clinical and Scientific Need

Deep Vein Thrombosis is the formation of a blood clot in a deep vein, or a vein found below the superficial surface of the body. These blood clots most commonly occur within the veins of the leg. Deep vein thrombosis can result in conditions such as a pulmonary embolism [3]. The blood clot in the leg can travel to the artery of the lung, in which the person affected can experience chest pain, low oxygen levels, chest pains, and in severe cases, sudden death. Many people that have blood clots will have a swollen, warm, painful leg, while others experience no symptoms at all.

The CDC states that as many as 900,000 people are affected by this condition every year [8]. There are many risk factors for this condition, so a large population of people has a good chance of developing this condition at some point in their life. Risk factors include vein injury that is a result of surgery or athletics, limited mobility for a long period of time, and obesity. Genetics and aging are also other factors that can contribute to the development of this condition.

The complications of vein thrombosis can be life-threatening, but when diagnosed early there is a low chance that the patient will experience serious complications from this condition. There is a clinical need for medical devices that can identify when a patient is experiencing this condition. Impedance plethysmography is a fast, non-invasive, and easy-to-understand method for the diagnosis of vein thrombosis. There is a need to design more reliable, user-friendly, low-cost, and portable impedance plethysmographs, which was the goal of our project. 

Existing Products

Photoplethysmography (PPG)​ - This device is typically a pulse oximeter that transmits light and records how much is absorbed versus how much is reflected and picked back up by the device. Blood has a higher absorption of light than surrounding tissues, so the more absorption that occurs, the higher amount of blood that is traveling through the vessel [1]. Significant changes in blood volume can be a good indication that a blood clot is present. Available devices have low-cost components, are non-invasive, and are convenient to use. The downside is that this method has not been well studied yet, so a deeper understanding of how to interpret the signals produced by these devices is necessary in order for it to be deemed a very accurate method for monitoring blood flow.

Ultrasound- Doppler ultrasound uses high-frequency sound waves to monitor blood flow in the veins of the body. A transducer sends and receives the signal and creates real-time images of the blood velocity and direction. This procedure relies on changes in acoustic properties and the direction of the sound waves that are sent in order to reconstruct an accurate picture [2]. There is software that can analyze the images to produce graphs or video loops that can be used to analyze the flow through a vessel. This procedure is accurate and can show multiple orientations of the vessel. There is also no threat of radiation exposure. However, ultrasound devices can be expensive and you need a certified medical professional to interpret the results.

Quantaflo- Quantaflo is a medical device that helps physicians to diagnose and monitor Peripheral Artery disease by using volume plethysmography [12]. It takes arterial measurements at different locations on the body: the Brachial, Posterior Tibial, and Anterior Tibia. The sensor is a transducer that can detect changes in arterial blood volume, which will then send a DC signal to a computer. There is an algorithm that processes the signal and calculates the probability that the patient has a blood clot. In a study performed by Rooke et al Quantaflo was able to correctly diagnose patients in 80.2% of cases.  

Design Constraints

This is a device that drives current through a human.  The device must be under the recommended limits for medical devices in regard to current. Ensuring that we built a device that prioritized safety was our most important constraint.  If the device were even semi-unsafe, it would have been unusable. The impedance plethysmograph we created needed to avoid microshock or any other electrical malfunctions that could result in shocking the body. We tested and used our device on our limbs, rather than any vessel close to the heart so that we avoided any complications associated with passing an electrical signal across the heart. We also used a low current, below 1.5 milliamps, which is in the safe range of current to apply to the body, so it would not interfere with any signals in the body or shock the user [7].

Our device needed safety precautions built-in so that it protected against and accounted for individual differences, such as sweaty or wet skin, cuts, or any other circumstances that would affect the resistance of the skin. Our device has a low signal-to-noise ratio so that it is clear what the body's response is to the applied current and the miscellaneous biopotentials in the body do not affect the analysis. As the body is not a perfect or controllable system, our device needs to have precise filtering and amplification to separate the noise of the body from the actual signal.

Our final constraint that affected the building and creation of our device is that the design must be based on parts and equipment that are easy to acquire or are already in the UW Bioengineering circuits lab. Although there was a budget for this project, it was easiest to come up with solutions while working in the lab based on the parts on hand, rather than waiting for certain resistors or op amps to get ordered. The parts found in the lab were not guaranteed to be brand new and we had to spend the time to test each part individually before using them to make sure that if we experienced a problem in our device that it is due to poor design and not a broken part.

Design Specifications

Our main design specification was creating an impedance plethysmograph with an accurate voltage reading and resistance translation, that is fully functioning, and safe to use. We accomplished this by following recommended current and voltage limits which ensures the safety and accuracy of our device extends to a wide range of people and circumstances. The recommended current limit for devices is around 1.5 milliamps, with 5 milliamps being the threshold for feeling shocked and 10 milliamps are approximately the lowest current before the “can’t let go effect” starts to occur, so our goal was to create a circuit that drove less than 1.5 milliamps through the body [7].

The main benchmark for the signal was to achieve a clear graph with little noise. This was achieved through targeted and precise filtering, as well as testing parts before using them in the circuit. We also implemented a potentiometer in the Howland current source circuit, at the node between R2 and R4 (see Howland Circuit section below) to ensure a perfect resistor balance. In addition to having clear graphs, the device should also be able to be powered by batteries, so that it is not necessary to rely on a function generator in order to power the circuit. This was achieved by building a relaxation oscillator circuit to be used with 2 9 volt batteries.

Initially, our design comprised of real-time processing, in LabVIEW, and a fully mobile device. However, after completing the project and building all the necessary circuit components to do so, we discovered that LabVIEW and the data acquisition device that was available in the lab were not able to sample and process the signal fast enough to display accurate output readings in real-time. There would be a major time delay or a major decrease in the number of samples that could be acquired in a certain time frame, so using signal processing machines such as the oscilloscope proved to be a better option for our project. Future work would involve creating better hardware in place of the current DAQ and incorporating a graphical user interface with the processing capability we desired for our device. 

Prototype Description

Part 1: Relaxation Oscillator Circuit 

Relaxation oscillators generate a changing voltage at a particular frequency. They do this by charging and discharging a capacitor. This relies on having 2 components of the circuit that will charge and discharge the capacitor automatically. The bottom 2 resistors essentially act as a voltage divider between the op amp’s output and ground. When the output of the op-amp is the highest at Vcc (9 V in our design) this “voltage divider” holds the positive input of the op-amp at 1⁄2 Vcc. It holds it there until the capacitor also charges to 1⁄2 Vcc. When this point is reached the inverting input has become more positive than the non-inverting input. The output of the op-amp then drops to -Vcc. The capacitor will then discharge until the capacitor’s charge is 1⁄2 -Vcc. At this point, the non-inverting input has become more negative than the inverting input and the output of the op-amp goes back to Vcc. This cycle continuously repeats to generate an oscillating square wave output that oscillates between -9 and +9V at a specific frequency. The Vin going into the Howland current source needs to be held at -9V. Our goal, however, is to send an oscillating AC current (i.e. sine wave) into the body, so the fact that the input voltage goes between -9V and 9V is not really important in that sense and actually produces the result we want.

The circuit also makes sense from a biomedical standpoint because we will eventually want to send an oscillating current through the body, so sending an oscillating voltage into our current source will yield an oscillating current from our current source. We were aiming for a frequency of 12.7 kHz, as this is the frequency value commonly used in industry. To calculate frequency we used the frequency equation shown below. Having a current at a frequency of 12.7 kHz makes sense because the signal being passed through the body must be different from the DC currents that naturally occur in the body. No other current is going to be going through the body that quickly, so we will be able to differentiate the signal we passed in from those that are always going through the body. This circuit essentially modulates our signal so that it can be passed through the body. This means that we will have to demodulate the signal after it is passed through the body.  

Figure 1(Above left): Our circuit diagram for our relaxation oscillator

Figure 2 (Above Right): Our results were obtained in the oscilloscope, measuring a frequency of 12.77 kHz.

Part 2: Howland Current Source Circuit

The Howland current source circuit is a current pump based on a current bridge incorporated with an op-amp (6). The circuit depends on the resistors being perfectly in balance according to the ratio R1/R2 = R3/R4 which we ensured by adding a potentiometer at the node to split resistance such that resistance R1 and R3 are balanced.  

Figure 3: Howland current source circuit diagram. 

This circuit relies on the principle that current through resistor one (R1) equals the current through resistor two (R2) and the current through resistor three (R3) equals the sum of the current through the body and the current through resistor four (R4) [11]. If R2/R1 then equals R4/R3 and the voltage at the positive terminal is essentially the same as the voltage at the negative terminal then the following set of equations can be derived:  

For the safety of the user, the desired current going through the body (i_body) is below 1.5 milliamps, so we calculated the value of R3 based on the input voltage and this desired current level. We tested our circuit using Ohm’s Law: Voltage = Current * Resistance, for a 150-ohm resistor substitute for the “body”. Using the amplitude of our signal we calculated that we had achieved a current of 1 milliamp, which was even better than we expected.  

Part 3: High Pass Filter

The addition of the high pass filter further filtered and cleaned up the signal after it was passed through the body. It is set to a cut off frequency of around 7.25 kHz so that the circuit is cutting out the noise from biopotentials/miscellaneous electrical signals in the body.

Part 4: Envelope Detector Circuit (ADC)

The signal comes into the op-amp and diode - which ensures current only flows in one direction - and then goes to the resistor/capacitor. Here it charges the capacitor to the max amplitude of the signal, which is what appears in the oscilloscope. If the maximum amplitude is decreased if the op-amp received feedback that the amplitude has changed and the resistor that is in parallel with the capacitor is used to dissipate the extra charge so that fluctuations in the signal can be tracked. The envelope detector isn't a one-time detector but rather continuously detects max amplitude. This circuit also demodulates the previously modulated signal. The resistor and capacitor essentially act as a low pass filter for the signal, which removes the carrier frequency that we created with the relaxation oscillator circuit. So in combination with the high pass filter, we have bandpass filtered the signal to both remove biopotential low-frequency noise and to remove the carrier frequency. The envelope detector functions as an analog to digital converter so that the signal can be put directly into the Data Acquisition Device.

Test Method

We tested all of our components with a multimeter to make sure that we were using desired resistance and capacitance values. We frequently checked our relaxation oscillator frequency and current source by observing the signals in the oscilloscope. We also debugged our circuit by tracing the flow of our circuit, either by eye or by writing down what all components were connected to versus what they should have been connected to. We also measured the signal coming out of certain components by attaching a wire to the oscilloscope input channel and measuring the signal after certain components. This was especially helpful in finding broken/loose components or in realizing that we had accidentally sent a component to ground.

Once we had a high level of confidence that our circuit had all the necessary safety precautions needed to attach to the human body, we attached electrodes to an arm and connected the arm in series with the circuits. One electrode was attached to the deltoid while another was attached closer to the wrist. We had multiple subjects flex their arms and watched as the heartbeat type wave fluctuated in amplitude in response to the increase in resistance to blood flow.  

Fabrication Procedure

In building our device we first attached a positive terminal, negative terminal, and ground from the power supply to our first breadboard. The positive terminal had to be connected to each individual positive power supply input for every op-amp. The same was true for the negative power supply inputs. When we ran out of space on our first breadboard we had to attach more breadboards in order to expand our circuit. This meant attaching wires that connected the positive and negative power supplies to the new breadboard and doing the same for ground. For the last breadboard, we attached we accidentally flipped the direction of the board, so that the positive sign label connected to the negative sign label on the new board and vice versa. This was something we had to remember and keep in mind when building our last board so that we did not make a mistake such as hooking up the op-amp power supplies incorrectly.

We started off using longer wires, but the board began to get crowded, so wire cutting was helpful to help us save time tracing our flow and space on our boards. After the first 2 circuit components were placed on the breadboards we realized the immense number of wires necessary so we redid the first two sections and neatened up the wires to make troubleshooting easier.

We also wanted to make our device transportable, which was achieved by powering our device with batteries. We did this by creating a relaxation oscillator circuit to be used immediately following the batteries to create the waveform we desired. There were no battery connector caps left in the lab, so we connected our batteries to the breadboards via 3 clamp cables, one from +9V on battery 1 to the positive circuit terminal, the next from -9V on battery 2 to the negative circuit terminal, and the third from the negative terminal on battery 1 to the positive terminal on battery 2 to complete the circuit.  

Evaluation/Results

In the end, we were able to create a working impedance plethysmograph, which met the majority of our initial goals for the project. We met our safety constraint, by creating a circuit that drives 1 milliamp through the body. Our final signal was clear and free from noise, and it met the criteria of at least 1 V in amplitude so that it is easy to see changes in the signal. We were also able to create a relaxation oscillator circuit so that we could power our impedance plethysmograph with batteries so that it could be a mobile device. However, to make our device fully mobile, our first iteration of the design involved LabVIEW real-time processing. We were not able to accomplish this due to the limitations in LabVIEWs sampling frequency. To adjust from this setback, we created the necessary circuitry components to convert our analog signal to a digital signal, so that in the future it would be easy to manipulate our design into one that could be processed digitally.

We also initially planned to use 4 electrodes in our design, 2 to drive current through the limb and 2 to measure voltage changes, but we were able to improve upon this and use only 2 electrodes. We discovered that it was rather unnecessary to use all 4 electrodes, as the body can be put in series with the Howland op-amp and the high pass filter, which then makes it so the electrodes send the same current flow from the op-amp output through the body. While that occurs, voltage changes are being measured across the body, using 2 wires that are connected to the oscilloscope and in series with the body on the breadboard.  

In response to flexing, you can see a slight change in the yellow line placement, indicating that the resistance detected by the envelope detector increased. There is also a positive amplitude change in the bottom graph, however, it is harder to discern. This confirms that we have a working impedance plethysmograph, as a flexing event increases the resistance to blood flow, much like a blood clot would increase resistance. The flex test shows that our device can accurately track changes in resistance in the blood.  

COMSOL Model

Description of the model

We chose a 2D asymmetric model. We built 4 rectangles, from radius equals zero out it was bone, blood, muscle, and then skin. We then added two points to our diagram, which acted as a “band” for which we could send current. The one at the bottom was set to an electric potential of zero, which acted as our ground, while the one at the top was set to the current density that is in the current density equation below. We then had to change the types of materials we were using to create a more accurate representation of our limb. We also changed the material properties such as density and electrical conductivity, as shown in the table below. We had the electrical conductivity of the skin set to an oscillating value, since we are sending an oscillating current into the body.

Type of Study

We started with a stationary study, then went to a time-dependent study. 

• Point 1: radius 0.101 m, z = 0.15 m

• Point 2: radius 0.101 m, z = 0.05 m 

• Calculation for normal Current density on the top segment: 

Our current value/Surface area of segment = 1/(2π*0.101*0.05)

• Electrical potential on the bottom: 0 (Ground)

• Physics: AC/DC (Electric Currents) 

As expected, in our model there is a hot and cold spot, corresponding to the 2 electrode bands. The bottom band was the ground, which is represented as a dark blue band as the voltage there is 0. The top band was the electrode that was directly connected to the end of the Howland Current Source circuit, which is represented by the bright red band with a voltage of 3 volts. The model shows the permeation of the voltage through the different layers, which shows the top outer layer having the highest concentration, with the concentration decreasing as the voltage goes through each layer. By the time the voltage reaches the bone on the upper half, it has decreased by about 1 volt, whereas from the bottom outer layer to the bone shows an increase of 1 volt. This behavior makes sense for our project, as it confirms that the voltage is essentially following a crescent shape, going from the top electrode to top skin to top muscle/blood/bone then flowing down and leaving through the bottom electrode.