New wearable digital health device tracks EKG and lactate levels

Engineers at the University of California San Diego have developed a new flexible wearable device that for the first time simultaneously measures electrocardiogram (EKG) heart signals and tracks levels of lactate, a marker of physical activity. The Chem-Phys patch could have a wide range of applications, including helping athletes improve performance and monitoring patients with heart disease.

Hybrid patch design rationale and fabrication

The Chem–Phys hybrid multi-sensor system must be compact and easy to wear in a location that offers adequate access to both electrocardiogram signals and perspiration for lactate measurements. The design must also minimize sensor-body motion, must minimize co-interference between the sensing modalities and be low-cost. These requirements motivate a flexible epidermal electronic design that can be worn on the chest and fabricated using screen-printing technology.

The design of the sensing system is shown in Fig. 1. The biosensors were fabricated via conventional low-cost screen-printing technique (conceptually illustrated in Fig. 1a) utilizing custom-designed stencils (photograph in Fig. 1b). The biosensing patches were printed onto a highly flexible, thin polyester sheet (50 μm thickness) for realizing highly conformable sensor patch that adheres well to the human skin without causing any discomfort. An array of fabricated sensors is shown in Fig. 1c. The total patch size was dictated by the bipolar electrocardiogram electrodes, which must be separated by a minimum distance to attain a high-quality signal48. Typically, single-lead monitoring systems, such as the present design, are used for basic heart monitoring, arrhythmias diagnosis or studying the effect of exercise on the heart, and are placed in the vicinity of the conventional V1–V6 chest-lead locations. Electrode size, separation and placement parameters were determined through a series of experiments involving the placement of Ag/AgCl-based electrocardiogram electrodes of various sizes (1 × 1, 1.5 × 1.5, 1.5 × 1 and 2 × 2 cm2) and separation distances (1–6 cm) on subjects with different chest sizes, and observing the resulting electrocardiogram waveforms. The study revealed that a compact patch that provides favourable electrocardiogram signal could be realized by placing 1.5 × 1.5 cm2 electrocardiogram electrodes across the V1 and V2 lead sites with an inter-electrode distance of 4 cm, thereby measuring from the vantage point of the septal surface of the heart as suitable for diagnostics of arrhythmias and the effects of exercise on the heart. This sets an upper-end size of the patch to be 7 × 2 cm2. The chest region is not only convenient for measurement of electrocardiogram, but also has a high-sweat rate during physical excursion49,50, and can thus serve as an appropriate location to also measure lactate levels in human perspiration. In addition, the epidermis and muscle tissues over these locations do not experience complex 3D strains and remain fairly stable even during intense physical activities, making measurements here especially convenient. Since the performance of amperometric lactate electrodes is not compromised by reducing their dimension, they were fabricated between the two electrocardiogram electrodes, as shown in Fig. 1d. Each of the three electrodes have an active area of 3 × 2.5 mm. The working electrodes were printed using prussian blue ink due to the high selectivity of prussian blue towards hydrogen peroxide, a byproduct of the enzymatic oxidation of lactate38,51 (Fig. 1e). The reference electrode was printed using Ag/AgCl. Since sweat can provide an alternate electrically conductive pathway between the electrocardiogram electrodes and also between the electrocardiogram and amperometric electrodes, thus leading to a potential distortion of the recorded electrocardiogram signal, a printed hydrophobic layer of Ecoflex was used to separate the amperometric biosensor from the electrocardiogram electrodes. This effectively increases the impedance between the electrocardiogram and amperometric electrodes via sweat, thus minimizing the cross-talk between the two sensors. The entire Chem–Phys patch is highly flexible and can be smoothly mated on curved surfaces. Such flexibility is crucial for achieving unobtrusive wearable devices that cause no hindrance or irritation to the wearer.

Figure 1: Fabrication and function of the Chem–Phys hybrid sensor patch. (a) Schematic showing the screen-printing process. (b) Image of the Chem–Phys printing stencil. (c) An array of printed Chem–Phys flexible patches. (d) Image of a Chem–Phys patch along with the wireless electronics. (e) Schematic showing the LOx-based lactate biosensor along with the enzymatic and detection reactions. (f) Block diagram of the wireless readout circuit. Full size image

The Chem–Phys patch was interfaced to a custom-PCB featuring a potentiostat and analogue-to-digital converter for amperometric data acquisition, an AFE for electrocardiogram data acquisition, and a BLE chip for wireless transmission (Fig. 1d,f).

In-vitro characterization of the lactate biosensor

Lactate concentration in human sweat depends on a person’s metabolism and level of exertion, and typically ranges from 0 to 25 mM (ref. 52). A wide linear-detection range, coupled with a fast response time is thus essential for continuous epidermal monitoring of lactate. The operating potential of −0.1 V (versus to Ag/AgCl) was selected based on the onset potential for electro-oxidation of lactate by the fabricated biosensor, obtained during cyclic voltammetry studies. When the biosensor comes in contact with lactate, the immobilized LOx enzyme catalyses the oxidation of lactate to generate pyruvate and H 2 O 2 . The prussian blue transducer then selectively reduces the H 2 O 2 to generate electrons to quantify the lactate concentration (Fig. 1e). Figure 2a shows the amperometric response of the lactate biosensor to increasing lactate concentrations in the physiological range of 0–28 mM. It is evidenced from this figure that the biosensor responds linearly to the lactate concentrations in this range with a sensitivity of 96 nA/mM.

Figure 2: In-vitro characterization of Chem–Phys hybrid patch. (a) Amperometric response to increasing lactate concentration from 0 to 28 with 2 mM additions in phosphate buffer (pH 7.0). Applied voltage=−0.1 V versus Ag/AgCl. (b) Electrocardiogram signals using 3M Red Dot electrodes (top), and printed electrocardiogram sensor (bottom). Full size image

On-body characterization of the electrocardiogram electrodes

The ability of the printed electrocardiogram electrodes to record electrocardiogram signals was validated by comparing recordings from the fabricated electrodes with commercially-available 3M Red Dot electrocardiogram electrodes. As illustrated in Fig. 2b, on-body electrocardiogram signals recorded for the same subject using commercial and fabricated electrodes at the same location have similar morphologies when acquired using the same AFE circuitry. All on-body experiments were performed in strict compliance with the guidelines of Institutional Review Boards (IRB) and were approved by the Human Research Protections Program at University of California, San Diego (Project name: Epidermal Electrochemical Sensors and Biosensors. Project number: 130,003).

Epidermal evaluation of the Chem–Phys patch

The Chem–Phys hybrid patch (Fig. 3a) was fabricated and applied to three healthy male subjects on the fourth intercostal space of the chest (Fig. 3b). Dynamic changes in sweat-lactate levels and electrocardiogram signals were measured continuously during a bout of intense cycling. To ensure that the anaerobic metabolism was invoked, subjects were asked to mount a stationary cycle and maintain a steady cycling cadence while the cycling resistance increased periodically as illustrated in Fig. 3c.

Figure 3: On-body test configuration. (a) A photograph of Chem–Phys hybrid patch. (b) Location of the Chem–Phys patch for mounting on the human body—the fourth intercostal space of the chest. (c) Cycling resistance profile for on-body tests. (d) Effect of amperometric measurement on the electrocardiogram signal before cycling (no sweat state) and during cycling (sweating state). Full size image

Since electrocardiogram measurements were made via bipolar high-impedance electrodes, and lactate measurements were made by applying a constant potential via a low-impedance potentiostat output and measuring current, there is a possibility that a change in the applied potentiostat voltage (for example, during start-up) could interfere with electrocardiogram measurements during the settling time of the potentiostat. At the same time, sweat consists of many ions and could thus act as an electrically conductive medium that can shunt the lactate and electrocardiogram sensors, or the two electrocardiogram electrodes together. Co-sensor interference and shunting effects were mitigated by geometrically separating the lactate and electrocardiogram electrodes and printing two vertically oriented hydrophobic layers were next to the lactate biosensor, thereby facilitating flux of new perspiration across the biosensor itself, while minimizing shunting between the lactate and electrocardiogram sensors. To validate performance under concurrent hybrid sensing scenarios, the Chem–Phys sensor was mounted on a human subject and set to continuously record electrocardiogram before, during, and immediately after turning on the −0.1 V potentiostat output. Experimental results, obtained via a wireless Bluetooth link as shown in Fig. 3d, reveal that the potentiostat has a negligible effect on the morphology of the electrocardiogram signals, irrespective of whether the subject was in a resting or cycling state.

To validate performance under realistic conditions, the Chem–Phys patch was tested on three subjects during 15–30 min of intense cycling activity; continuous time-series results during each experiment are shown in Fig. 4. At the commencement of the cycling activity, each subject’s heart rate, extracted from electrocardiogram data, was within the normal resting range of 60 to 120 beats per minute (b.p.m.)53. At the same time, a negligible current response was measured by the lactate biosensor due to the lack of perspiration. With time, the resistance for cycling was increased, causing the subjects to exert increasing levels of effort to maintain constant cycling speed. This resulted in increasing heart rate and generation of sweat. At the onset of perspiration, lactate is released from the epidermis, and is selectively detected by the LOx-based biosensor. As the resistance increases, the sweat-lactate concentration too increases, as illustrated in Fig. 4a–c, showing a correlation between physical exertion, heart rate and, after a physiologic time delay, lactate generation. As the cycling continued, the sweat rate for each subject increased, leading to the well-documented phenomenon of dilution factor that causes decrease in the lactate concentration42. The final stage of the cycling bout involved a 3 min cool-down period. During this phase, as expected, the heart rate normalized back near to the normal resting heart rate. At the same time, the lactate concentration measured by the lactate biosensor continued to decrease.

Figure 4: Real-time on-body evaluation of the Chem–Phys hybrid patch showing the lactate levels and heart rate for three human subjects. (a–c) The corresponding blue plots represent the real-time lactate concentration profiles for each subject, while, the red plots depict the heart rate data obtained by the electrocardiogram electrodes of the Chem–Phys patch. The black plots correspond to the heart rate data recorded by the Basis Peak heart rate monitor. Typical real-time electrocardiogram data obtained before, during and after the cycling bout for each subject is also shown. (d) Additional heart rate data from subject #1. (e) Response of the control amperometric sensor (without LOx enzyme) for subject #1. Full size image

The lactate biosensor data for each subject resembles the expected sweat-lactate profile for increasing intensity workouts37. To validate that lactate, not other sweat constituents, was specifically measured, a control experiment in which an unmodified (LOx-free) amperometric biosensor was used under the same experimental conditions as above to subject #1. As shown in Fig. 4e, the control biosensor leads to a negligible current response without the presence of LOx, confirming the high selectivity of the lactate biosensor. To validate electrocardiogram data over long time series, even under the presence of experimentally-induced motion, heart rate as extracted from the electrocardiogram data is benchmarked against a commercial wristband heat rate monitor (BASIS) for subjects 1 and 3. Extracted heart rate data matched the wrist-worn device with a Pearson’s correlation coefficient of r=0.975. These on-body studies illustrate that the hybrid patch could monitor sweat lactate and electrocardiogram in a continuous and simultaneous manner, and that the hydrophobic barrier between the sensors assisted in minimizing potential cross-talk between the two sensing modalities. The data also demonstrates that such a barrier had minimal effect on the supply of oxygen to the enzyme electrode required for biocatalytic detection of lactate.