Implementation Techniques for Transcutaneous Carbon Dioxide Monitoring: Approaches for Wearable Smart Health Applications.

Wearable smart health applications aim to continuously monitor critical physiological parameters without disrupting patients' daily activities, such as giving a blood sample for lab analysis. For example, the partial pressure of arterial carbon dioxide, the critical indicator of ventilation efficacy reflecting the respiratory and acid-base status of the human body, is measured invasively from the arteries. Therefore, it can momentarily be monitored in a clinical setting when the arterial blood sample is taken. Although a noninvasive surrogate method for estimating the partial pressure of arterial carbon dioxide exists (i.e., transcutaneous carbon dioxide monitoring), it is primarily limited to intensive care units and comes in the form of a large bedside device. Nevertheless, recent advancements in the luminescence sensing field have enabled a promising technology that can be incorporated into a wearable device for the continuous and remote monitoring of ventilation efficacy. In this review, we examine existing and nascent techniques for sensing transcutaneous carbon dioxide and highlight novel wearable transcutaneous carbon dioxide monitors by comparing their performance with the traditional bedside counterparts. We also discuss future directions of transcutaneous carbon dioxide monitoring in next-generation smart health applications.

Optimizing Transcutaneous Oxygen Measurement Sites on Humans.

This study utilizes an optical method of transcutaneous oxygen sensing that has the potential to revolutionize at-home care. This technique is based on quenching the luminescence of a platinum porphyrin film. Since oxygen quenches luminescence, its lifetime is further measured to assess the partial pressure of transcutaneous oxygen diffusing through the skin. Unlike conventional transcutaneous oxygen monitors that use electrochemical sensors, the luminescence-based sensor allows the use of dry electrodes that do not require heating and reduce the risk of accidental skin irritations or burns. These properties not only improve patient safety but also allow the creation of miniature wearable transcutaneous oxygen sensors for continuous and accurate remote respiratory monitoring. To this end, it is critical to assess the efficiency of the wearable sensor by determining the optimal location for its placement on the body. Depending on the location on the body, physiological factors such as blood flow rate and skin thickness affect dermal perfusion of transcutaneous oxygen. In this work, four healthy volunteers participated in subject testing. We assessed each participant at the following locations: thumb, top of the wrist, forearm, thigh, and shin. All locations consistently reported accurate and reliable data. Among them, the thumb demonstrated shorter settling times and the most uniform luminescence lifetime values.

A Transcutaneous Carbon Dioxide Monitor Based on Time-Domain Dual Lifetime Referencing.

The partial pressure of arterial carbon dioxide plays a critical role in assessing the acid-base and respiratory status of the human body. Typically, this measurement is invasive and can only be taken momentarily when an arterial blood sample is drawn. Transcutaneous monitoring is a noninvasive surrogate method that provides a continuous measure of arterial carbon dioxide. Unfortunately, current technology is limited to bedside instruments mainly used in intensive care units. We developed a first-of-its-kind miniaturized transcutaneous carbon dioxide monitor that utilizes a luminescence sensing film and a time-domain dual lifetime referencing method. Gas cell experiments confirmed the monitor's ability to accurately identify changes in the partial pressure of carbon dioxide within the clinically significant range. Compared to the luminescence intensity-based technique, the time-domain dual lifetime referencing method is less prone to measurement errors caused by changes in excitation strength, reducing the maximum error from  âˆ¼ 40% to  âˆ¼ 3% and resulting in more reliable readings. Additionally, we analyzed the sensing film by investigating its behavior under various confounding factors and its susceptibility to measurement drift. Finally, a human subject test demonstrated the effectiveness of the applied method in detecting even slight changes in transcutaneous carbon dioxide, as small as  âˆ¼ 0.7%, during hyperventilation. The prototype, which consumes 30.1 mW of power, is a wearable wristband with compact dimensions of 37 mm× 32 mm.

A Prototype Wearable Device for Noninvasive Monitoring of Transcutaneous Oxygen.

Transcutaneous oxygen monitoring is a noninvasive method for measuring the partial pressure of oxygen diffusing through the skin, which strongly correlates with changes in dissolved oxygen in the arteries. Luminescent oxygen sensing is one of the techniques for assessing transcutaneous oxygen. Intensity- and lifetime-based measurements are two well-known methods used in this technique. The latter is more immune to optical path changes and reflections, making the measurements less vulnerable to motion artifacts and skin color changes. Although the lifetime-based method is promising, the acquisition of high-resolution lifetime data is crucial for accurate transcutaneous oxygen measurements from the human body when skin is not heated. We have built a compact prototype along with its custom firmware for the lifetime estimation of transcutaneous oxygen with a provision of a wearable device. Furthermore, we performed a small experiment study on three healthy human volunteers to prove the concept of measuring oxygen diffusing from the skin without heating. Lastly, the prototype successfully detected changes in lifetime values driven by the changes in transcutaneous oxygen partial pressure due to pressure-induced arterial occlusion and hypoxic gas delivery. The prototype resolved a minimum change of 1.34 ns in a lifetime that corresponds to 0.031 mmHg in response to slow changes in the oxygen pressure in the volunteer's body caused by hypoxic gas delivery. The prototype is believed to be the first in the literature to successfully conduct measurements in human subjects using the lifetime-based technique.

Wireless Photometry Prototype for Tri-Color Excitation and Multi-Region Recording.

Visualizing neuronal activation and neurotransmitter release by using fluorescent sensors is increasingly popular. The main drawback of contemporary multi-color or multi-region fiber photometry systems is the tethered structure that prevents the free movement of the animals. Although wireless photometry devices exist, a review of literature has shown that these devices can only optically stimulate or excite with a single wavelength simultaneously, and the lifetime of the battery is short. To tackle this limitation, we present a prototype for implementing a fully wireless photometry system with multi-color and multi-region functions. This paper introduces an integrated circuit (IC) prototype fabricated in TSMC 180 nm CMOS process technology. The prototype includes 3-channel optical excitation, 2-channel optical recording, wireless power transfer, and wireless data telemetry blocks. The recording front end has an average gain of 107 dB and consumes 620 µW of power. The light-emitting diode (LED) driver block provides a peak current of 20 mA for optical excitation. The rectifier, the core of the wireless power transmission, operates with 63% power conversion efficiency at 13.56 MHz and a maximum of 87% at 2 MHz. The system is validated in a laboratory bench test environment and compared with state-of-the-art technologies. The optical excitation and recording front end and the wireless power transfer circuit evaluated in this paper will form the basis for a future miniaturized final device with a shank that can be used in in vivo experiments.

Respiratory Monitoring: Current State of the Art and Future Roads.

In this article, we present current methodologies, available technologies, and demands for monitoring various respiratory parameters. We discuss the importance of noninvasive techniques for remote and continuous monitoring and challenges involved in the current "smart and connected health" era. We conducted an extensive literature review on the medical significance of monitoring respiratory vital parameters, along with the current methods and solutions with their respective advantages and disadvantages. We discuss the challenges of developing a noninvasive, wearable, wireless system that continuously monitors respiration parameters and opportunities in the field and then determine the requirements of a state-of-the-art system. Noninvasive techniques provide a significant amount of medical information for a continuous patient monitoring system. Contact methods offer more advantages than non-contact methods; however, reducing the size and power of contact methods is critical for enabling a wearable, wireless medical monitoring system. Continuous and accurate remote monitoring, along with other physiological data, can help caregivers improve the quality of care and allow patients greater freedom outside the hospital. Such monitoring systems could lead to highly tailored treatment plans, shorten patient stays at medical facilities, and reduce the cost of treatment.

Towards a Tri-Color Wireless Photometry System for the Monitoring of Neuronal Activity in the Basal Forebrain and Hippocampus.

Healthy cholinergic function is important for brain function, and disruption of the system is thought to be the cause of dementia, including Alzheimer's disease. The 'Cholinergic Hypothesis' theorizes that cognitive decline is due disruption of the cholinergic system, defined by the low concentration of neurotransmitters such as acetylcholine (ACh) and neurotransmitter-releasing elements such as calcium ions (Ca2+). The ability to measure ACh and Ca2+ concentrations enables researchers to make inferences on the relationship between these indicators that play a role in the onset of neurological conditions. Current commercial devices have one or more of the following limitations: i) they are tethered making it difficult to verify in naturally behaving animal subjects, ii) they are capable of only measuring a single indicator at any given time, or iii) they have multiple shanks that penetrate the cortex. We propose a tri-color miniaturized photometry system capable of optically stimulating indicators in neurons located in the hippocampus and basal forebrain and optically reading the neurons' response. The resulting device has an average gain of 123 dB and a power consumption of 29 mW, comparable to other state-of-the-art devices.

An Infra-Red-Based Prototype for a Miniaturized Transcutaneous Carbon Dioxide Monitor.

New types of miniaturized biomedical devices transform contemporary diagnostic and therapeutic techniques in medicine. This evolution has demonstrated exceptional promise in providing infrastructures for enabling precision health by creating diverse sensing modalities. To this end, this paper presents a prototype for transcutaneous carbon dioxide monitoring to diversify the measurable critical parameters for human health. Transcutaneous carbon dioxide monitoring is a noninvasive, surrogate method of assessing the partial pressure of carbon dioxide in the blood. The partial pressure of carbon dioxide is a vital index that can help understand momentarily changing ventilation trends. Therefore, it needs to be reported continuously to monitor the ventilatory status of critically ill patients. The proposed prototype employs an infrared LED as the excitation source. The infrared emission, which decreases in response to an increasing carbon dioxide concentration, is applied to a thermopile sensor that can detect the infrared intensity variations precisely. We have measured the changes in the partial pressure of carbon dioxide in the range of 0-120 mmHg, which covers humans' typical values, 35-45 mmHg. The prototype occupies an area of 25 cm2 (50 mm × 50 mm) and consumes 85 mW power.

A Noninvasive Miniaturized Transcutaneous Oxygen Monitor.

Transcutaneous monitoring is a noninvasive method to continuously measure the partial pressures of oxygen and carbon dioxide that diffuse through the skin and correlate closely with changes in blood gases. However, the contemporary commercially available electrochemical-based technology requires a heating mechanism and a bulky, corded, and expensive sensing unit. This study aims to demonstrate a prototype noninvasive, miniaturized monitor that uses luminescence-based technology to measure the partial pressure of transcutaneous oxygen, a surrogate of the partial pressure of arterial oxygen. To be able to build a robust measurement system, we conducted experiments to understand the temperature and humidity dependence of oxygen-sensitive platinum-porphyrin films. We performed a detailed analysis of both intensity and lifetime measurement techniques. To verify the performance, we tested the prototype in a small ex-vivo experiment involving three healthy human volunteers. We measured variations in the partial pressure of transcutaneous oxygen values due to pressure-induced arterial and venous occlusions on the volunteers' fingertips. The system resolves changes in the partial pressure of oxygen from 0 to 418 mmHg in the lab bench-top testing, covering the medically relevant range of 50-150 mmHg. Under fixed humidity, temperature, and the partial pressure of oxygen conditions, the sensor shows a 2% drift over 60 hours. The prototype consumes 9 mW of power from a 2.2 V external DC power supply.

A Trimodal Wireless Implantable Neural Interface System-on-Chip.

A wireless and battery-less trimodal neural interface system-on-chip (SoC), capable of 16-ch neural recording, 8-ch electrical stimulation, and 16-ch optical stimulation, all integrated on a 5 ×  3 mm2 chip fabricated in 0.35-µm standard CMOS process. The trimodal SoC is designed to be inductively powered and communicated. The downlink data telemetry utilizes on-off keying pulse-position modulation (OOK-PPM) of the power carrier to deliver configuration and control commands at 50 kbps. The analog front-end (AFE) provides adjustable mid-band gain of 55-70 dB, low/high cut-off frequencies of 1-100 Hz/10 kHz, and input-referred noise of 3.46 µVrms within 1 Hz-50 kHz band. AFE outputs of every two-channel are digitized by a 50 kS/s 10-bit SAR-ADC, and multiplexed together to form a 6.78 Mbps data stream to be sent out by OOK modulating a 434 MHz RF carrier through a power amplifier (PA) and 6 cm monopole antenna, which form the uplink data telemetry. Optical stimulation has a switched-capacitor based stimulation (SCS) architecture, which can sequentially charge four storage capacitor banks up to 4 V and discharge them in selected µLEDs at instantaneous current levels of up to 24.8 mA on demand. Electrical stimulation is supported by four independently driven stimulating sites at 5-bit controllable current levels in ±(25-775) µA range, while active/passive charge balancing circuits ensure safety. In vivo testing was conducted on four anesthetized rats to verify the functionality of the trimodal SoC.