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An Injectable System for Subcutaneous Photoplethysmography, Accelerometry, and Thermometry in Animals
Abstract and Figures
Obtaining physiological data from animals in a non-obtrusive and continuous manner is important to veterinary science. This paper demonstrates the design and deployment of a miniaturized capsule-based system for subdermal injection to provide real-time and continuous heart-rate, movement, and core-body-temperature measurements. The presented device incorporates sensors for photoplethysmography, motion detection, and temperature measurements. A Bluetooth-Low-Energy enabled microcontroller configures the sensors, digitizes the sensor information, and wirelessly connects with external devices. The device is powered by a CR425 battery for this paper, and various other battery solutions are available based upon the use case. The design uses only commercially available integrated circuits in order to reduce the development cost and be modular. The encapsulation is a combination of medical epoxy and poly(methyl methacrylate) that fits within a 6-gauge hypodermic needle. The preliminary evaluation of the device included an in vitro assessment of its thermal response and measurement accuracy, the impact of one-month implantation on surrounding tissue, the power consumption with duty-cycling of various sensors, and a measurement of physiological signals in a rat and a chicken. Having a form factor and implantation method similar to existing devices for animals, this novel system is a useful platform for both scientists and veterinarians to better study a diverse range of animals.
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... This size of the implant fits into a commercially available standard 6-gauge surgical needle and allows for an easier implantation method that minimizes the incision size. The contributions of this paper include the addition of biopotential hardware, packaging innovations to accommodate electrode interfaces for bioelectric measurements and to enhance biocompatibility, a significant reduction of power consumption by the implant's electronics, and the development of a receiver platform for data aggregation with respect to the earlier versions of the system [39], [40]. Sections II, III, and IV of the paper contain a description of the implant's hardware development, embedded software, and manufacturing techniques, respectively. ...
... The developed injectable electronic system includes various sensors, front-end circuits, a microcontroller with a wireless radio system, and a power management unit (Fig. 1). Our earlier design had a printed circuit board (PCB) size of 3.6 × 30 mm 2 [40]. This new design retained all of those previously discussed components along with the inclusion of a new ECG & BioZ AFE and other circuit strategies such that the system is still the same size as before. ...
... The CR pin-type batteries have a lower self-discharge rate and a more compact construction making them suitable for our application. Previously we had used CR425 and CR435 type batteries that have a nominal voltage of 3.0 V [40]. A few drawbacks with those batteries were the inability to be recharged, limited shelf life, difficulty in soldering the terminals, and the nominal voltage being marginally suitable for the green LEDs. ...
Unobtrusive acquisition of physiological and behavioral data from freely moving animals is important to many applications including animal research, veterinary science, animal husbandry, pet monitoring, etc. This paper reports a miniaturized, injectable, and multimodal implant for real-time measurements of heart rate, breathing rate, movement, and subcutaneous temperature with future extensions to blood pressure and oxygen saturation. To estimate these vital signs, the presented device incorporates sensors of various modalities: photoplethysmography, electrocardiography, accelerometry, magnetometry, and thermometry. A rechargeable battery drives the system containing a system-on-chip with Bluetooth low energy capability and multiple sensor front-end circuits. The implant electronics are isolated from the animal’s extracellular fluid by a dual-layer encapsulation of biomedical epoxy and poly(methyl methacrylate) that fits into a 6-gauge surgical needle to allow for subcutaneous injection. Electrically conductive epoxy is used to create electrodes on the surface of the encapsulation for biopotential measurements. With a 3-meter wireless range from a custom receiver, this implant can continuously transmit data from all the sensors for 20 hours, which can support 2-3 months of duty-cycled and intermittent recording between battery recharges. The system was tested in vivo where the acquired heart rate and breathing rate estimations showed an error of less than 2 beats per minute compared to the gold standard. Longer-term evaluation of tissue reaction showed an acceptable level of immune responses with minimal effect on the sensing performance. This novel system has the potential to provide new insights with greater depth in veterinary research and practice, and animal welfare management.
... The miniaturized wireless system consists of commercial-off-theshelf (COTS) ICs and communicates via Bluetooth Low Energy (BLE) protocol. The overall system also includes an IMU and a temperature sensor and is encapsulated into an injectable implant [94]. The designed system successfully acquired PPG signals using light sources of different wavelengths from rats and chickens during in vivo experiments. ...
... In this work, the same material (Epo-Tek ® H20E, Epoxy Technology, Inc., Billerica, MA, USA) is utilized to create the electrode surfaces in the implant. The method of electrode preparation is improvised to fit with the packaging method described in [94]. This process of making conductive epoxy electrodes provides more flexibility in terms of physical outcome. ...
... This work aims to develop a minimally-invasive injectable sensor system for animals using commercially available ICs to wirelessly monitor both physiological indicators and activity patterns. The presented multimodal implant (Figure 6.1) is an enhanced version of our previous designs [94], [97], [136] and ...
The relentless pursuit of financial efficiency has encouraged the development of intensive animal management systems, where the care of the animal is sometimes compromised. As the physical or emotional stress on the animals summons the conscience of the consumers, the public's interest in animal welfare is continuing to rise. While several qualitative and quantitative measures are used to assess the long-term welfare of an animal, the physiological and behavioral states of the animals are the only quantifiable measures of the short-term responses of animal welfare. Moreover, studying the vital signs [e.g., heart rate (HR), breathing rate (BR), blood pressure (BP), core body temperature, etc.] and behavioral traits of freely moving animals can provide significant insights to veterinarians, animal researchers, and biomedical engineers. Monitoring of animals is also necessary for the pharmaceutical industries, where the safety and efficacy of human drugs are tested on animal models. Wireless sensor systems attached to individual animals can provide specific physio-behavioral information about each animal continuously. However, an externally attached device on a freely moving animal would have unfavorable impacts on its natural behavior and comfort. Moreover, the recordings from a wearable sensor would suffer from the obstruction created by the layer of skin and fur. An implantable system, on the other hand, can avoid the difficulties related to the attachment of sensors to the animal and can be minimally obtrusive, depending on the size of the implant. In this research, a subcutaneously injectable implant equipped with several sensing capabilities is developed using commercial-off-the-shelf components.
First, the transparently encapsulated implant includes a biophotonic front-end circuit that can acquire photoplethysmography (PPG) signals. The designed system successfully recorded PPG signals using light sources of different wavelengths from rats and chickens during \textit{in vivo} experiments. As PPG systems are highly power-consuming, a low-power custom-integrated PPG front-end circuit has been validated by developing a wearable wristband for humans that has the potential to reduce the implant’s battery usage in the future. Second, the developed system is capable of biopotential (electrocardiography or ECG) and bioimpedance (BIOZ) measurements that can provide deeper insight into the cardiovascular system. Despite the difficulties of interfacing conductive electrodes in implants, two techniques for manufacturing electrode surfaces on the implant are proposed, and the accuracy of the system is validated with a commercial ECG amplifier during the in-vivo experiments. The combination of this biophotonic and bioelectric sensing would enable the estimation of HR, BR, oxygen saturation in the blood (pulse oximetry), pulse transit time (PTT) which is correlated with BP, tissue hydration level, etc. Third, a temperature sensor has been added to read the core body temperature, which has been validated using an in-vitro setup. Lastly, an inertial measurement unit (IMU) that integrates an accelerometer and a magnetometer are included in the system. Accelerometry can track various micro and macro activities by classifying the tri-axial data, whereas magnetometry can register an animal's physical orientation.
All these sensor electronics, along with a wireless microcontroller and a pin-type battery, are coated with biocompatible materials and packaged into a capsule-shaped cylinder with a diameter of 4 mm. This miniaturized implant fits into a commercially available injector (similar to the ones used for RFID tags) and allows for an easier injection method avoiding any surgical procedure on the animal. The contribution of this research includes the design and development of the implantable system, optimization of the hardware and software to reduce the power consumption, packaging innovations to accommodate electrical interfaces within the injectable form factor, and the in-vivo animal experiments for the validation of individual sensors.
... physical activity monitoring and health care applications [4] [5]. In these applications, the sensors are powered by battery, thus high energy efficiency is required to extend battery life. ...
... If ∆ > 0, the switch S2 shuts down earlier than the switch S4 does and the resistance of 2 is larger than that of 4 . Thus, most of the charge 2 from S4 is leaked ( 2 ) and the charge injected to C2 ( 2 ) is not zero and it is dominated by the charge 1 , ...
This paper proposes a clock strategy to improve the precision of power-efficient readout circuit for capacitive sensor. To achieve high power efficiency, capacitive sensor such as MEMS accelerometer is designed with open-loop architecture rather than close-loop one. In the open-loop architecture, the capacitance variation of sensing element is limited to femto-farad level in order to overcome nonlinearity problem. However, due to this limitation, the signal charge from sensing element is weak and the interference charge due to coupling capacitance between clock wires and sensing electrodes becomes a significant issue. Therefore, split clock bus is employed to meet this challenge, but the split clock bus introduces the timing mismatch which causes the charge injection sensitive to fabrication process and circuit operating voltage. As a result, the input offset, the variation of the offset and the nonlinearity of readout circuit will increase, and this will lead to reduction of precision. In this work, a clock scheme named "multi-nested clocks" is proposed to address the charge injection problem. The multi-nested clocks are demonstrated in a readout circuit fabricated using a 0.18-μ m BCD process. The measurement results show that compared to the readout circuit using traditional clock, the readout circuit using the multi-nested clocks significantly reduces the equivalent input offset from 1.66fF to 0.25fF, the offset variation from 1.4fF to 0.2fF and the nonlinearity from 5.5% to 0.9%.
... However, even with these securing measures, the weak attachment of the devices makes them susceptible to motion artifacts, impacting data accuracy [13]. Recently, injectable microchip implants, conventionally employed for animal identification, have shown its great potential as a promising alternative for monitoring animal health [14]- [17]. These injectable devices operating subcutaneously can improve coupling with tissue and enhance SNR compared to conventional wearables. ...
Utilizing injectable devices for monitoring animal health offers several advantages over traditional wearable devices, including improved signal-to-noise ratio (SNR) and enhanced immunity to motion artifacts. We present a wireless application-specific integrated circuit (ASIC) for injectable devices. The ASIC has multiple physiological sensing modalities including body temperature monitoring, electrocardiography (ECG), and photoplethysmography (PPG). The ASIC fabricated using the CMOS 180 nm process is sized to fit into an injectable microchip implant. The ASIC features a low-power design, drawing an average DC power of 155.3 μW, enabling the ASIC to be wirelessly powered through an inductive link. To capture the ECG signal, we designed the ECG analog frontend (AFE) with 0.3 Hz low cut-off frequency and 45-79 dB adjustable midband gain. To measure PPG, we employ an energy-efficient and safe switched-capacitor-based (SC) light emitting diode (LED) driver to illuminate an LED with milliampere-level current pulses. A SC integrator-based AFE converts the current of photodiode with a programmable transimpedance gain. A resistor-based Wheatstone Bridge (WhB) temperature sensor followed by an instrumentation amplifier (IA) provides 27–47 °C sensing range with 0.02 °C inaccuracy. Recorded physiological signals are sequentially sampled and quantized by a 10-bit analog-to-digital converter (ADC) with the successive approximation register (SAR) architecture. The SAR ADC features an energy-efficient switching scheme and achieves a 57.5 dB signal-to-noise-and-distortion ratio (SNDR) within 1 kHz bandwidth. Then, a back data telemetry transmits the baseband data via a backscatter scheme with intermediate-frequency assistance. The ASIC’s overall functionality and performance has been evaluated through an
in vivo
experiment.
... In order to provide the veterinarians and animal scientists a tool to assess the health and behavior of animals, we previously presented an implant with optical and motion-sensing capabilities which can be injected subcutaneously [9]. In the present work, we have included additional circuitry to enable the study of subcutaneous ECG in this form factor. ...
A major bottleneck in the manufacturing process of a medical implant capable of biopotential measurements is the design and assembly of a conductive electrode interface. This paper presents the use of a novel 3D-printing process to integrate conductive metal surfaces on a low-temperature co-fired ceramic base to be deployed as electrodes for electrocardiography (ECG) implants for small animals. In order to fit the ECG sensing system within the size of an injectable microchip implant, the electronics along with a pin-type lithium-ion battery are inserted into a cylindrical glass tube with both ends sealed by these 3D printed composite electrode discs using biomedical epoxy. In the scope of this paper, we present a proof-of-concept in vivo experiment for recording ECG from an avian animal model under local anesthesia to verify the electrode performance. Simultaneous recording with a commercial device validated the measurements, demonstrating promising accuracy in heart rate and breathing rate monitoring. This novel technology could open avenues for the mass manufacturing of miniaturized ECG implants.Clinical relevance- A novel manufacturing process and an implantable system are presented for continuous physiological monitoring of animals to be used by veterinarians, animal scientists, and biomedical researchers with potential future applications in human health monitoring.
... Thus, PPG is considered a likely candidate to address the challenges associated with ECG obtained using implants provided a suitable sensing solution can be designed. Implantable PPG solutions have been developed for, e.g., sheep [27] and other mammals [28]. Although potentially relevant, such solutions are proprietary and either require additional, external interfaces for power and data collection/processing, or depend on radiobased data transfer, making them infeasible for use in fish in seawater. ...
Background
Welfare challenges in salmon farming highlights the need to improve understanding of the fish’s response to its environment and rearing operations. This can be achieved by monitoring physiological responses such as heart rate (HR) for individual fish. Existing solutions for heart rate monitoring are typically based on Electrocardiography (ECG) which is sensitive to placement and electrode orientation. These factors are difficult to control and affects the reliability of the principle, prompting the desire to find an alternative to ECG for heart rate monitoring in fish. This study was aimed at adapting an optical photoplethysmography (PPG) sensor for this purpose. An embedded sensor unit measuring both PPG and ECG was developed and tested using anesthetized Atlantic salmon in a series of in-vivo experiments. HR was derived from PPG and compared to the ECG baseline to evaluate its efficacy in estimating heart rate.
Results
The results show that PPG HR was estimated with an accuracy of 0 . 7 ± 1 . 0% for 660 nm and 1 . 1 ± 1 . 2% for 880 nm wavelengths, respectively, relative to the ECG HR baseline. The results also indicate that PPG should be measured in the anterior part of the peritoneal cavity in the direction of the heart.
Conclusion
A PPG/ECG module was successfully adapted to measure both ECG and PPG in-vivo for anesthetized Atlantic salmon. Using ECG as baseline, PPG analysis results show that that HR can be accurately estimated from PPG. Thus, PPG has the potential to become an alternative to ECG HR measurements in fish.
Microcontrollers and field-programmable gate arrays have been largely leveraged in scientific instrumentation since decades. Recent advancements in the performance of these programmable digital devices, with hundreds of I/O pins, up to millions of logic cells, >10 Gb/s connectivity, and hundreds of MHz multiple clocks, have been accelerating this trend, extending the range of functions. The diversification of devices from very low-cost 8-bit microcontrollers up to 32-bit ARM-based ones and a system of chip combining programmable logic with processors make them ubiquitous in modern electronic systems, addressing diverse challenges from ultra-low power operation, with sub-µA quiescent current in sleep mode for portable and Internet of Things applications, to high-performance computing, such as in machine vision. In this Review, the main motivations (compactness, re-configurability, parallelization, low latency for sub-ns timing, and real-time control), the possible approaches of the adoption of embedded devices, and the achievable performances are discussed. Relevant examples of applications in opto-electronics, physics experiments, impedance, vibration, and temperature sensing from the recent literature are also reviewed. From this bird-eye view, key paradigms emerge, such as the blurring of boundaries between digital platforms and the pervasiveness of machine learning algorithms, significantly fostered by the possibility to be run in embedded devices for distributing intelligence in the environment.
Intestinal electrical stimulation via implants is already used to treat several disorders, like constipation or incontinence. Stimulation parameters are most often empiric and not based on systematic studies. One prerequisite to evaluate effects of intestinal electrical stimulation (IES) is a direct assessment of intestinal motility. Some common methods are strain gauge transducers or manometry. With both methods it is not possible to record the exact 3-dimensional movement. Therefore, we established a new method to record gastrointestinal motility with ultra miniaturized accelerometers, directly glued to the outer surface of the stomach, small intestine and colon. With this technique, we were able to record precise local motility changes after electrical stimulation. Due to the low energy demand and the small size of the system, it is potentially useful for chronic measurements at multiple sites of the intestinal tract. We will present our first results regarding stimulation dependent motility changes using up to 8 implanted accelerometers in an acute pig model. OAPA
Heart rate variability (HRV) is commonly used to assess autonomic functions and responses to environmental stimuli. It is usually derived from electrocardiographic signals; however, in the last few years, photoplethysmography has been successfully used to evaluate beat-to-beat time intervals and to assess changes in the human heart rate under several conditions. The present work describes a simple design of a photoplethysmograph, using a wearable earlobe sensor. Beat-to-beat time intervals were evaluated as the time between subsequent pulses, thus generating a signal representative of heart rate variability, which was compared to RR intervals from classic electrocardiography. Twenty-minute pulse photoplethysmography and ECG recordings were taken simultaneously from 10 healthy individuals. Ten additional subjects were recorded for 24 h. Comparisons were made of raw signals and on time-domain and frequency-domain HRV parameters. There were small differences between the inter-beat intervals evaluated with the two techniques. The current findings suggest that our wearable earlobe pulse photoplethysmograph may be suitable for short and long-term home measuring and monitoring of HRV parameters.
Background:
Persistent use of real-time continuous glucose monitoring (CGM) improves diabetes control in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D).
Methods:
PRECISE II was a nonrandomized, blinded, prospective, single-arm, multicenter study that evaluated the accuracy and safety of the implantable Eversense CGM system among adult participants with T1D and T2D (NCT02647905). The primary endpoint was the mean absolute relative difference (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference measurements through 90 days postinsertion for reference glucose values from 40 to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor longevity. The primary safety endpoint was the incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days postinsertion.
Results:
Ninety participants received the CGM system. The overall MARD value against reference glucose values was 8.8% (95% confidence interval: 8.1%-9.3%), which was significantly lower than the prespecified 20% performance goal for accuracy (P < 0.0001). Ninety-three percent of CGM values were within 20/20% of reference values over the total glucose range of 40-400 mg/dL. Clarke Error Grid analysis showed 99.2% of samples in the clinically acceptable error zones A (92.4%) and B (6.8%). Ninety-one percent of sensors were functional through day 90. One related SAE (1.1%) occurred during the study for removal of a sensor.
Conclusions:
The PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings through the intended 90-day sensor life with a favorable safety profile.
Animal-assisted therapies (AAT) are becoming increasingly common to help hospitalized patients, especially in oncology units. There is a critical need for methods and technologies that can enable a quantifiable understanding of AAT to objectively demonstrate its efficacy and improve its efficiency. In this paper, we present our preliminary efforts towards the development of wireless sensor systems to simultaneously detect the related behavioral (activity level, movement, stroking) and physiological signals (heart rate/variability) of humans and animals during their interaction. To detect heart rate, we tested two different techniques based on wearable or contactless electrocardiography. In this preliminary evaluation, we were able to assess these parameters successfully and identify the design challenges towards deployment of these systems in larger clinical studies.
Accelerometers are used to remotely monitor activity in various species in studies that quantify pain, document behavioural patterns, and measure individual activity differences. Studies validating accelerometers typically quantify various active states; however, targeting states specific to periods of inactivity, such as sitting, sleeping, and standing, has the potential to more accurately quantify inactive behaviours commonly associated with behavioural changes related to pain, sickness, or injury. Our objectives were two-fold: first, validate a commercially available accelerometer (Actical®) for quantifying inactivity in laying hens and, second, compare inactivity levels between hens with severely fractured keel bones and hens with minimal to no keel damage. Correlation between the inactivity level as measured by the accelerometer compared to live, focal observation of stationary, inactive behaviours was high; therefore, the Actical® accurately quantifies inactive states in laying hens. Following validation, the Actical® accelerometer was used to quantify inactivity level differences between hens with or without keel-bone damage. Severely fractured hens spent less time motionless, than hens with minimal to no keel damage. Further investigation into inactivity differences related to keel status before and after acquisition of keel fractures is warranted. Use of the accelerometer has the potential to improve animal welfare research by quantifying the effect of pain or sickness on activity level, mapping daily activity patterns, and measuring individual differences in general activity.
An animal's behaviour can be a useful indicator of their physiological and physical state. As resting, eating, walking and ruminating are the predominant daily activities of ruminant animals, monitoring these behaviours could provide valuable information for management decisions and individual animal health status. Traditional animal monitoring methods have relied on labour intensive, human observation of animals. Accelerometer technology offers the possibility to remotely monitor animal behaviour continuously 24/7. Commercially, an ear worn sensor would be the most suitable for the Australian sheep industry. Therefore, the aim of this current study was to determine the effectiveness of different methods of accelerometer deployment (collar, leg and eartag) to differentiate between three mutually exclusive behaviours in sheep: grazing, standing and walking. A subset of fourteen summary features were subjected to Quadratic Discriminant Analysis (QDA) with 94%, 96% and 99% of grazing, standing and walking events respectively, being correctly predicted from ear acceleration signals. These preliminary results are promising and indicate that an ear deployed accelerometer is capable of identifying basic sheep behaviours. Further research is required to assess the suitability of accelerometers for behaviour detection across different sheep classes, breeds and environments.
Knowledge of suckling behaviour in beef calves is important for understanding the health and wellbeing of both cows and calves. The present study was conducted to explore the use of tri-axial accelerometers to identify suckling bouts and suckling duration per bout in beef calves under free-range conditions. Three experiments were conducted: Experiment 1 was conducted to develop a model to characterise suckling in calves; Experiments 2 and 3 were conducted to apply the model when cattle were managed in pastoral paddock conditions. One Holstein Friesian and one Droughtmaster cow-calf pair were used in Experiment 1 for 2 days. The tri-axial accelerometer was fitted to a neck collar of the Droughtmaster calf and at the bottom and the right side of a halter on a Holstein Friesian calf on consecutive days. The initial model was developed using data collected from one calf for one day only to classify accelerometer data into suckling and non-suckling periods. In Experiment 2, 24 Belmont Red calves with accelerometers attached on the right side of the halters were visually observed for 10 days. The model was applied to raw data obtained through use of the accelerometers and the model could be used to successfully identify 98.8% of suckling bouts when compared with visually recorded behavioural data. The average suckling duration per bout recorded by accelerometers was 9.72 ± 0.20 min, whereas visually it was 9.32 ± 0.19 min. In Experiment 3, 20 Brahman calves fitted with accelerometers were visually observed for 6 h for 3 consecutive days. The model could be used to identify 95% of suckling bouts from the accelerometer data, corresponding to total number of suckling bouts observed visually. The average suckling duration per bout recorded by accelerometers was 13.69 ± 1.82 min, while with visual observations was 12.23 ± 1.77 min. The results indicate that accelerometers are a very effective tool to record suckling behaviour in beef calves in pastoral paddock conditions.
We studied circadian rhythms of body temperature and locomotor activity in antelope ground squirrels (Ammospermophilus leucurus) under laboratory conditions of a 12L:12D light-dark cycle and in constant darkness. Antelope ground squirrels are diurnally active and, exceptionally among ground squirrels and other closely related members of the squirrel family in general, they do not hibernate. Daily oscillations in body temperature consisted of a rise in temperature during the daytime activity phase of the circadian cycle and a decrease in temperature during the nighttime rest phase. The body temperature rhythms were robust (71% of maximal strength) with a daily range of oscillation of 4.6 °C, a daytime mean of 38.7 °C, and a nighttime mean of 34.1 °C (24-h overall mean 36.4 °C). The body temperature rhythm persisted in continuous darkness with a free-running period of 24.2 h. This pattern is similar to that of hibernating species of ground squirrels but with a wave form more similar to that of non-hibernating rodents. Daily oscillations in body temperature were correlated with individual bouts of activity, but daytime temperatures were higher than nighttime temperatures even when comparing short episodes of nocturnal activity that were as intense as diurnal activity. This suggests that although muscular thermogenesis associated with locomotor activity can modify the level of body temperature, the circadian rhythm of body temperature is not simply a consequence of the circadian rhythm of activity.
