Emerging

Blood Gas Monitors

How they can help with COVID-19

Ulkuhan Guler, Ian Costanzo, and Devdip Sen

T
he world has been in tated almost every nation across the ration (SpO2)], even in patients who
combat with COVID- globe, from the Far East to Europe, appear to be breathing normally [2].
19 since December Latin America, Russia, and India. Under normal conditions, these lev-
2019. The United States Around the world, physicians have els are far below those that cause
has been paralyzed, been documenting their experiences death [3]. For most people, the nor-
with the highest number of cases and under the heavy siege of the pan- mal SpO2 $ 93% at sea level, requir-
more deaths than any other coun- demic, emphasizing the presence ing no therapy [4].
try. However, the disease has devas- of silent hypoxia and hypoxemia Silent hypoxia occurs after severe ac­­
[1]. This deceptive side of COVID-19 ute respiratory syndrome coronavirus 2
Digital Object Identifier 10.1109/MSSC.2020.3021839 leads to deficient levels of oxygen (the strain of the coronavirus respon-
Date of current version: 18 November 2020 (O2) [e.g., 60% or less blood O2 satu- sible for COVID-19) attacks the lungs’

© IEEE 2020. This article is free to access and download, IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 33
along with rights for full text and data mining, re-use and
Authorized
analysis
licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.

Physicians have been documenting their
experiences under the heavy siege of the
pandemic, emphasizing the presence of silent
hypoxia and hypoxemia.
cells, causing the air sacs to collapse
and leading to a decline in the O2 lev-
els in the blood. However, since the
lungs are not yet filled with fluids,
they can still expel carbon dioxide
(CO2) [1]. Patients try to compensate
for the low O2 levels by breathing
faster and deeper. This early phase
is called silent hypoxia because
patients do not present with short-
ness of breath caused by the buildup
of CO2 in the lungs. As the disease
progresses, it is reported that fluid
can start building in the lungs. The
lungs are unable to expel CO2, and
the deadlier second phase of the
disease begins in 20 –30% of the
patients [1]. Unfortunately, by the
time this visible symptom presents,
the damage has already been done to
the lungs.
As in the COVID-19 example, respi-
ratory failure is unpredictable in nature
and can become life threatening in a
matter of minutes [5]. Changes in vital
sign parameters often reveal impor-
tant markers of the onset of a dete-
rioration in health, leading to severe
consequences. Frequent alterations in
respiration parameters reflect com-
promised neurological and cardiopul-
monary functions [6]. Quantifying the
real-time dynamics and physiological
distributions of blood gas measure-
ments of CO2 and O2 are imperative to
both clinicians and researchers. These
data provide a detailed understand-
ing of physiological and pathological
conditions. In this context, long-term
aggregation of the data from respira-
tory parameters measurement may
offer novel insights into respiratory
diseases that are not fully understood,
such as COVID-19.
The ability to continuously moni-
tor a person’s respiration rate and
effort, coupled with his or her blood
gas content of O2 and CO2, would
provide significant and invaluable
34 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE
Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
insight into the individual’s well-being
[7], [8]. Patients with respiratory dis-
orders, from mild issues to severe
complications requiring ­mechanical
ventilation, are at risk for acute
res­­piratory failure [9]. Changes in a
patient’s respiratory rate can also
indicate a critical medical event that
may require immediate intervention
and admission to the intensive care
unit (ICU) [10]. Factors such as post-
operative respiratory complications,
premature births, severe infection
and trauma, certain psychiatric and
psychological conditions such as
claustrophobia and anxiety, and
diseases including chronic obstruc-
tive pulmonary disease (COPD) and
COVID-19 can cause abnormal respi-
ratory activity. Therefore, it is of the
utmost importance to have the abil-
ity to sense and measure respiratory
parameters in a continuous, reliable,
and accurate manner across different
conditions [11], [12].
The need for continuous and re­­
mote monitoring is clearly e ­ vident
for COVID-19-infected patients as well
as for the contact tracing of poten-
tial patients. Due to the threat of the
disease and the likelihood of getting
infected, many patients are reluc-
tant to visit health-care centers. By
the time a patient starts to experi-
ence shortness of breath, indicating a
buildup of fluid in the lungs, it may be
too late. Many patients are admitted to
hospitals only after COVID-19-related
pneumonia has reached an advanced
stage. This significant delay in treat-
ing patients who enter the emergency
room has critically strained health-
care systems throughout the world.
This strain has led to a high mortality
rate, especially in the early weeks of
the COVID-19 breakout. A miniatur-
ized blood gas monitor attached to a
patient’s body can help with monitor-
ing individuals in their home. A person
should not have to choose between
a fear of getting sick and receiving
proper care.
Since the severity of COVID-19 var-
ies widely depending on the individ-
ual who contracts it, we must respond
to the infection by personalizing the
treatment. Roughly 30% of COVID-19
patients have cloudy lungs, low lev-
els of O2 in their blood, and shortness
of breath [1]. These are indications
of the improper functioning of the
lungs. Surprisingly, a large number of
patients have normal-looking lungs
but low blood O2 [2], each requiring
a unique treatment. Patients with
shortness of breath require imme-
diate access to mechanical ventila-
tors. Those with only low O2 need
less-intensive therapy. In COVID-19
treatment, a side effect of mechanical
ventilation, which fills the lungs with
forced air to increase a patient’s intake
of O2, is damage to the thin air sacs of
the lungs. Because air sacs are respon-
sible for O2 exchange, damaged air
sacs simply exacerbate the situation.
As a result of the heavy use of ventila-
tors in the early phases of COVID-19
treatment, death rates have reached
60% in some ICUs. Studies have shown
that mechanical ventilation takes its
toll on the lungs [13]. Therefore, early
detection and treatment could lower
the number of deaths from COVID-19.
On the other hand, the sheer num-
ber of patients requiring intervention
has led to an acute shortage of ven-
tilators and put tremendous strain
on our fragile health-care systems.
Additionally, it has placed our health-
care workers and first responders
at high risk of contracting the virus.
Ventilating a patient is a complicated
procedure, consuming considerable
resources to administer and maintain
care. Connecting intravenous and
arterial lines for infusing medicine via
registered infusion pumps; admin-
istering sedatives to patients (who
often accidentally remove the breath-
ing tubes), and inserting breathing
tubes and bladder tubes are some
of the examples of the medical pro-
cedures that require an orchestrated
team of experts.
 In conclusion, remote and continu-
ous monitoring of blood gas content
with a miniaturized, noninvasive, and
comfortable device is essential, not
only for known respiratory diseases,
including COPD and sleep apnea in
adults and babies, but for uprising
diseases such as COVID-19. Moreover,
offering personalized medicine for
patients experiencing the same disease
in various conditions would be possi-
ble with remote and continuous moni-
toring of blood gas content. In this
article, we cover emerging blood gas
monitoring devices and techniques to
create the sensors and IC structures to
transform bulky benchtop instruments
into miniaturized, next-generation bio-
medical devices. We also explore cur-
rently available technologies, with a
short glance back to the evolution of
blood gas sensing systems.
State-of-the-Art Blood Gas
Monitoring Sensors
Today, many smartwatches and fit-
ness trackers come with sensors to
measure physiological parameters and
activity, such as heart rate and move-
ment, and support software to track
exercise and diet [18], [23]. Hospitals
are starting to use wearables that wire-
lessly transmit data to a base station
in a ward to monitor patients’ postsur-
gery conditions [24], [25]. Research-
ers are looking for ways to leverage
machine learning and artificial intel-
ligence to make these tools “smarter.”
These advancements have demon-
strated exceptional promise in provid-
ing an infrastructure for performing
medicine in a futuristic way, where
health-care providers and patients are
better connected and informed.
However, amid this transforma-
tion, there has been little progress
in miniaturizing respiration devices
to a suitable form factor for long-
term wear and comfort. Research and
development of wearables has heavily
focused on pulse oximeters and elec-
trocardiograms (ECGs) [20], [26]. The
respiration rate and blood O2 satura-
tion, well-known respiration param-
eters, are only a subset of respiration
parameters. Beyond that, there are
IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 35
Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
A miniaturized blood gas monitor attached
to a patient’s body can help with monitoring
individuals in their home.
more parameters, such as blood O2
and CO2 partial pressures, which
have medical significance and the
potential for being measured nonin-
vasively from the body.
Currently, in the hospital setting,
respiration parameters are observed
using bedside instruments with
wired probes attached to the patient.
The invention of these instruments
follows a pretty impressive history
that begins just before World War
II and includes rapid technological
development after 1970. Figure 1
offers a snapshot of the evolution of
respiration monitoring technologies
from 1956 to 2020.
Before the late 1950s, blood gas
analysis was performed using blood
samples drawn from an arterial or a
venous line. Arterial blood gas moni-
toring remains the gold standard for
respiration assessment. During the
late 1950s, inventors John W. Severing-
haus, A. Freeman Bradley, and Leland
Clark developed electrodes that would
enable the revolutionary electrochem-
ical transcutaneous sensors still used
today [27]. During the early 1970s,
Takou Aoyagi and Michio Kishi cre-
ated the first practical pulse oximeter,
under the Nihon Kohden Company.
They devised a mathematical formula
that distinguishes O2 absorption data
from pulse information. This way, pul-
satile noise is removed [16]. Through
the next two decades, noninvasive res­­
piration monitors became staples in
hospital wards around the world. In
particular, pulse oximetry began to
dominate through its relative simplic-
ity and ease of use.
Pulse oximeters are some of the
most widely used medical sensors and
are becoming commonplace in wear-
able fitness trackers [18], [23]. During
the 2010s, companies including FitBit
and Apple released high-quality health
and fitness trackers to the consumer
market. These products generated a
desire for smart and connected medi-
cal tools and for giving individu-
als more control over their well-being.
During the past couple of years, uni-
versities such as the University of Cali-
fornia, Berkley, Worcester Polytechnic
Institute, and Northwestern University
developed new and exciting respira-
tion monitoring devices [20]–[22].
This research has been driven by
concerns about effective remote and
continuous monitoring and patient
comfort. Improving the quality of
remote care has increased demand
for hospital-grade wearable medi-
cal devices. These new instruments
would enable medical professionals
to safely monitor patients from indi-
viduals’ homes, reducing long and
expensive hospital stays and poten-
tially speeding up recovery. In this
section, we briefly discuss the vari-
ous types of state-of-the-art respira-
tion probes and electrodes that are
in use in the health-care industry.
Pulse Oximeters:
Photoplethysmography
Photoplethysmography (PPG) is an opti-
cal method to measure the change
in blood volume in a capillary bed. A
pulse oximeter is an instrument that
illuminates the skin through LEDs,
typically placed on a fingertip or an
ear lobe, and it captures the transmit-
ted and reflected light with a photo-
detector (PD). It measures changes in
light absorption by the tissue. The
difference in light intensity is related
to the change in the blood volume to
the capillaries in the dermis and sub-
cutaneous tissue. Two wavelengths
of light, typically red and infrared,
are harnessed due to the different
absorption spectra for oxygenated
and deoxygenated hemoglobin. Some
pulse oximeters use green or blue
light instead of infrared [28]. The
ratio of these two waveforms is used
to infer the percentage of hemoglobin
 loaded with O2, which is also called a
patient’s SpO2.

Institute Integrated Circuits and

2020: Worcester Polytechnic
Pulse oximeters are valuable tools,

FIGURE 1:  A timeline of advancements in respiration monitoring from 1956 to 2020 [14]–[22]. PtcO2: partial pressure of O2; PaO2: arterial partial pressure of O2; PPG: photoplethysmogra-
Systems Lab demonstrates
as they enable medical practitioners

2020: Berkley demonstrates

an ASIC for a wearable

an ASIC for an implantable
and nonprofessionals, who have only

PtcO2 sensor [22].

minimal basic training, to easily moni-

PtcO2 sensor [21].

tor O2 saturation and heart rates. Pulse
oximeters measure peripheral O2
saturation. O2 saturation and O2 par-
tial pressure (or tension) are related

sensor with pulse oximetery

2019: SenTec introduces a
through the dissociation curve, given

combined PtcO2 and PO2

in Figure 2, which in many cases
enables O2 saturation to be used as
demonstrates a wearable pulse
2019: Northwestern University

a surrogate measurement of O2 par-

(OxiVent) [41].
tial pressure.
oximeter on a flexible

Pulse oximeters are not perfect,

organic photodiodes and LEDs [19].

and they do have some drawbacks.
substrate [20].

2018: Lim et al. publish flexible Many factors, such as acidity (pH),
PtcO2 monitoring optode using
temperature, hemoglobin count,
and the partial pressure of CO 2 ,
can shift the dissociation curve on
an individual basis. Additionally,
pulse oximeters have been found
with a PPG heartrate
2015: Fitbit releases

to provide inaccurate results and

the charge HR,

to have limited performance in cer-

fitness tracker

phy; ASIC: application-specified IC; pH: acidity; OLED: organic light-emitting diode; OPD: organic photodetector.
a wrist-warn

tain settings. Different skin colors

2007: Eberhard publishes a method
monitor.

can affect the absorption of the

1993: Larsen, Linnet, and Vesterager propose

sensing photons; t his ca n cause

a solid-state glass pH electrode for PtcCO2.
to optically measure PtcCO2.

erroneous readings if not corrected

[29]–[31]. Low blood pressure and
vasoactive drugs can also cause
algorithms to reduce errors
1995: Masimo introduces

in pulse oximeters due to

motion artifacts and poor

false readings [31], [32]. Another

issue related to poor perfusion is
that SpO2 readings from finger-tip
pulse oximetry change with limb
perfusion.

temperature, particularly if the fin-

gers and hands are too cold [33].
Motion artifacts from movement, a
1976: First commercial

widely studied problem, can cause

sensors are available.
values match PaO2 values

the American Physiological Society.)

1956: Clark invents a 1972: Aoyagi and Kishi develop
demonstrates that PtcO2

transcutaneous gas

pulse oximetery. (Source: [16];

when the skin is heated

reprinted with permission from

false readings and interrupt con-

HP OLV-5100 Ear Pulse Oximeter
1972: Lübbers group

tinuous measurements [34]–[36].

One major issue involves the pres-
ence of carboxyhemoglobin and
to 43–44°.

methemoglobin, such as in carbon

invent a CO2 and O2 monitoring device.

monoxide poisoning and methemo-

globinemia. These molecules have
1958: Severinghaus and Bradley

permission from The American

a bs or b a nce patterns similar to

(Source: [15]; reprinted with

oxyhemoglobin and therefore cause

platinum-based O2

falsely elevated readings [31].

Physiological Society.)

electrode [14].

The relative ease of use and abil-

ity to measure SpO2 and heart rate
make the pulse oximeter a valuable
tool from the operating room to the
ambulance and the home environ-
ment. However, some physicians have
concerns about overreliance on this

36 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 surrogate measurement. It should be
noted that oxygenation is not ventila-
tion. In many cases, patients have a
reasonable O2 saturation level but still
have a breathing problem due to high
CO2 levels. These high CO2 levels can
be caused by underlying conditions
that prevent the patient from exhaling
correctly. Therefore, in current prac-
tice, the invasive blood gas measure-
ment has not been entirely replaced.
Considering this need, we claim that
noninvasive multimode blood gas mon-
itoring solutions should be explored
[22], [38], [39].
reference silver (Ag)/Ag chloride elec- loss. This is known as retinopathy
trode. The potential difference caused of prematurity. Transcutaneous O2
by the pH can be related to the CO2 electrodes, such as those developed
concentration with the Henderson– by Clark [14] and later improved
Hasselbalch equation [42]. by Severinghaus [15], enable the
Historically, transcutaneous O2 accurate measurement of O2 with-
has been measured using Clark elec- out having to take an arterial blood
trodes. During the 1950s, concerns sample from infants.
grew over O2-related blindness in The Clark-style O2 electrode works
premature infants. If premature infants on the reduction reaction on a plati-
receive excessive O2, the underde- num cathode coupled with oxida-
veloped blood vessels in their eyes tion on an AG anode. The reduction
could be damaged, and the result- reaction generates a current that is
ing scar tissue can cause vision proportional to the concentration of

Electrochemical Transcutaneous 100

Electrodes 2.3 DPG
Transcutaneous sensors have been a 90 Temperature
mainstay in the medical field since PtcCO2
80
the 1970s. Severinghaus invented the pH
% Oxygen Saturation (SO2)

70 FHbF
first stable electrode for measuring FCOHb
CO2 in the blood in 1953, improv- 60 FMetHb 2.3 DPG
ing on Richard Stow’s electrode [27]. Temperature
50
Lelend Clark introduced the plati- PtcCO2
num (Pt)-based O2-sensing electrode 40 pH
in 1956 [14]. It has been used with
30
good success, especially with neonate
patients and in wound treatment. 20
Severinghaus would later improve
10
on that design and combine it with
his CO2 sensors. In 1993, Larsen and 0
0 10 20 30 40 50 60 70 80 90 100
Linnet published findings on a solid-
Partial Pressure of Oxygen (PtcO2) (mmHg)
state CO2 electrode that was more sta-
ble and reliable than previous designs
[40]. Electrochemical electrodes are FIGURE 2:  The relationship between blood saturation and blood partial pressure. Param-
eters that can shift this relationship are highlighted. Adapted from [37]. mmHG: millimeters
still the standard for transcutane- of mercury; DPG: disphosphoglycerate; HbF: fetal hemoglobin; COHb: carboxyhemoglobin;
ous measurements today. However, MetHb: methemoglobin.
newer optical methods may begin to
replace the 60-year-old technology
[17], [41]. An example cross section
Ag/AgCl Reference Electrode
of an electrochemical transcutane- Pt Electrode (O2) or
Electronics
ous sensor is illustrated in Figure 3. pH Electrode (CO2)
The basic concept for the electro- Housing
chemical transcutaneous CO2 elec- Heater Adhesive
trode is as follows. The CO2 diffuses Membrane
from the tissue through a CO2-perme-
able membrane to an electrolyte-cov- 42–45° C
ered glass electrode. The CO2 reacts Blood Gas Diffusion Epidermis
with the water in the solution, forming
carbonic acid and changing the elec- Derma
trolyte solution’s pH. The change in
the pH of the solution is related to the
concentration of CO2, which causes Subcutaneous Tissue
a potential difference to develop
between the glass electrode and the FIGURE 3: An electrochemical transcutaneous gas sensor. Ag/AgCl: silver/silver chloride; Pt: platinum.

IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 37

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 O2. Clark electrodes measure the
transcutaneous partial pressure of O2
150 (PtcO2). The PtcO2 is linearly related
to the arterial partial pressure of O2
(PaO2) at an increased temperature
of ~44° C, typically with a small dc
100
PtcO2 (mmHg)

offset due to O2 consumed by the tis-

sue and other metabolic processes
[43], as exhibited in Figure 4. Other
50 factors can impact the relationship
between the PtcO2 and PaO2, such as
the temperature to which the skin is
heated. A higher temperature brings
the partial pressure of O2 in the tissue
50 100 150 200
PaO2 (mmHg) closer to the arterial tension; however,
it also increases O2 consumption by
cells in the tissue.
Electrochemical sensors have a lag
FIGURE 4:  The relationship between the PtcO2 and PaO2. Adapted from [43].
time between a change in the arterial
tension and the value measured at
the sensor. The lag is approximately
15–30 s, with transcutaneous CO2
diffusing faster than transcutane-
ous O2 [44]. Electrochemical sensors
PD
also suffer long stabilization periods
(minutes) and drift; therefore, they
LED LED
require regular recalibration [8], [41],
[44]. The accuracy and measurement
Luminescent Sensing Film times of electrochemical transcu-
Epidermis taneous monitors can be im­­ proved
through local heating with tempera-
Blood Gas Diffusion
tures between 42 and 45° C. How-
Derma
ever, this heating creates local hot
spots, which can potentially damage a
patient’s skin.

Subcutaneous Tissue Photophysical O2 Probes

Luminescent O2 sensors for transcu-
(a) taneous sensing have been explored
0.12 since the 1980s. However, they fell
out of fashion with the popular-
0.1
Exciting ity and success of pulse oximetry.
Spectrum
Intensity (a.u.)

0.08 Recently, luminescent O2 sensors

Intensity

2
cO

have begun reemerging as a compact

Pt

Emission 0.06
g

Less O2 way to monitor transcutaneous O2,

in
s

Spectrum
ea

0.04 which will help overcome some of

cr

More O2 40 mmHg
In

the limitations of using pulse oxim-

450 650 0.02 120 mmHg
etry alone [22], [38], [39], [41]. Lumi-
Wavelength (nm) nescent O2 sensors are also finding
0
(b) 0 10 20 30 40 50 use in wound treatment to assess tis-
Time (µs)
sue oxygenation [21].
(c) Photophysical O2 sensors rely on
luminescence to detect O2. The sen-
sor consists of luminescent dyes sus-
FIGURE 5:  (a) A cross section of a luminescent O2 sensor. (b) A Stokes shift of luminescent
O2 sensing dye. (c) The luminescent lifetime of the sensor versus the O2 concentration. pended in a polymer matrix and is
a.u.: arbitrary unit. excited with an LED; the response is

38 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 measured with a PD, as depicted in
Figure 5. When the dye is exposed to
a short wavelength (i.e., blue light), it
reemits light at a longer wavelength
(red/orange). The intensity and life-
time of the luminescence are depen-
dent on the concentration of O2. In
low-O2 environments, a large num-
ber of photons are emitted by the
film. In the presence of O2, the light
is quenched as energy is transferred
to the O2 molecule instead of being
emitted as a photon. A PD circuit
measures the emitted photons’ life-
time (or intensity) to determine the
O2 concentration in the surrounding
environment of the dye.
Emerging Next-Generation
Blood Gas Monitors
Despite the massive efforts demon-
strated in creating a new portfolio
of next-generation smart and con-
nected biomedical devices, limited
studies have been presented for
wearable/implantable ­technology
in the critical field of blood gas
analysis. Transcutaneous blood gas
monitoring using electrochemical
probes and bedside units has been
quite successful in the past. However,
the presence of a heating element
has negatively affected the transi-
tion of the technology from bedside
monitoring to a long-term wearable.
Designing a heating element on a
wearable will drastically increase the
device size and power requirements,
limiting the ­wearable’s use for con-
tinuous, long-term monitoring. In
this section, we discuss emerging
next-generation blood gas monitor-
ing systems, including transcutane-
ous and PPG, particularly monitoring
O2 content.
Featured PPG-Based Monitors
PPG-Based Monitor in a System-on-
Chip With Bluetooth Low Energy
Work presented in [45] proposed an
all-in-one, battery-powered system-
on-chip (SoC) health-monitoring patch
for continuous evaluation in a home
setting. The SoC is designed in a
55-nm technology node that provides
an optimum solution for the cointe-
gration of advanced low-power ana-
log/radio frequency (RF) and digital
blocks. A system diagram of the PPG
readout is presented in Figure 6. The
PPG readout consists of a current-
sensing stage and a fully differential
transimpedance stage. A 16-b analog-
to-digital converter (ADC) with a digi-
tal-assisted dc-current-cancellation
loop follows the amplifier to maintain
a high dynamic range. The dc-can-
cellation loop helps to reduce the dc
component (the ambient component)
in the signal, facilitating a higher ac
gain and more dynamic range.
The SoC was integrated into a
disposable medical-grade encapsula-
tion, as presented in [26] and shown
in Figure 7. The wearable health patch
incorporates a pulse oximeter, a bio-
impedance sensor, a thermometer,
and an ECG. The system integrates the
SoC, external electrodes, LEDs, PDs,
Bluetooth Low Energy (BLE) antenna,

LED Readout FE
Digital
Driver –
+ – +
Current TIA / PPG
ADC CIC/FIR
Sensing INT
– + –
5 mA × 32 +

VBIA SN VBIA SP
5b dc Filter/
IDAC Register

Copied
M1 M2 N1 Signal N2
N1 N2
Current
VOPCM VONCM
VINP VINN VCG
VOP VON
– Signal –A VREFO
A1 + + A
+ 2 A4 +
VOPCM

VBIA SP Local Current – 3 –

Local VBIA SN
Feedback Feedback VONCM
N3 N4
Main Main
Feedback l1 l2 Feedback

Current-Sensing Stage TIA Stage With CMFB

FIGURE 6:  A system diagram of the PPG readout front end (FE). Adapted from [26]. TIA: transimpedance amplifier; ADC: analog-to-digital
converter; CIC/FIR: cascaded integrator-comb/finite impulse response; IDAC: inter-digital analog converter; CMFB: common-mode feedback;
INT: integer.

IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 39

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 and other matching circuitry on a
flexible printed circuit board (PCB).
Digital PPG-Based Monitor
As opposed to a well-controlled medi-
cal setting, biosignal acquisition in
a dynamic environment, such as a
home or an office, has been quite chal-
lenging. The signals degrade due to
many hard-to-control factors, includ-
ing motion artifacts, poor sensor
interfaces, environmental noise such
as power line coupling, and ambient
light. These external artifacts place
PPG LEDs and Photodiode
Electrodes
Temperature
demanding design specifications that
are necessary for any wearable de­­
vices. Work presented in [47] pro-
posed a multimodal biosensing SoC
that enables a reliable PPG-based
monitor sensor for live-use scenar-
ios. The PPG readout has a dynamic
range of 130 dB, which, according to
the authors’ best knowledge, is 11 dB
higher than any reported contempo-
rary device; hence, it is capable of tol-
erating strong ambient light.
The digital transimpedance ampli-
fier (TIA)-based approach in this article
Low Number of
Components
SoC
achieves the reported dynamic range
with no dc–serve loop requirement
in a dc-cancellation digital-to-analog
(DAC) converter. Its noise components
are akin to a conventional TIA, with-
out added ADC noise. The conversion
is processed in the digital domain,
enabling relatively easy digital sig-
nal process of the acquired data. The
architecture of the front end (FE) is
presented in Figure 8.
PPG-Based Monitor Dedicated to
Neonatal ICU Babies
A battery-free, wireless vital sign
monitoring system, with a soft and
noninvasive interface, has been pro-
posed in [20]. The so-called epider-
mal electronic system (EES) uses a
binodal pair of ultrathin modules, a
PPG sensor, and an ECG sensor. The
PPG EES consists of a pair of LEDs
(red and infrared), a PD, wireless
power circuits, an LED driver, an
inverting amplifier, analog circuits,
and a near-field communication
(NFC) SoC. A 14-b ADC digitizes the
captured signals. The RF capabili-
ties serve the dual purpose of data
communication and power transfer.
One should note that all the elec-
tronic components deployed in [20]
are off the shelf. The system dia-
gram is exhibited in Figure 9.

The PPG EES is mounted on an

Sensors Readouts for Storage Interface infant’s foot. The patch is designed
Data Collection
NTC
such that van der Waals forces are
Wired strong enough to adhere to the deli-
Sound
Temperature cate infant skin, with a minimal ther-
ECG ECG BIOZ mal load and mechanical strain. The
BIOZ
Sound encapsulation is water resistant,
Processing
PPG PPG improving system robustness. Water
resistance is necessary, as neonatal
ICU incubators have a humidity set-
01010101
Wireless ting of 80% to maintain temperature
homeostasis and prevent the dehy-
Power Management dration of premature infants.
Security
Data and Harvesting Charging Featured Fluorescent-Based
Application
Single Power
LDO(s)
dc–dc Monitors
Source Converters
Minimally Invasive O2 Monitor
The Lumee O2 platform has been
designed and developed to monitor
FIGURE 7:  The wearable health patch developed by the Interuniversity Microelectronics subcutaneous tissue O2 in the body,
­Center. Adapted from [26]. BIOZ: bioimpedance; LDO: Low dropout regulator. based on the principles of optical

40 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 spectroscopy and the phosphores- tion channel. The data transmis- the external piezo during the receive
cence quenching of metalloporphy- sion is performed by the amplitude mode after two times of flight follow-
rins [48], [49]. The system consists modulation of the ultrasound back- ing the transmission. The received sig-
of a hydrogel sensor, a pen injector, scattering, which is then received by nal is filtered, ­demodulated, amplified,
a console, and a spotlight reader
(Figure 10). The sensor implanted in
the subcutaneous tissue consists of
soft hydrogel with dimensions of 0.5
× 0.5 × 0.5 mm. The sensor is bio- LED Driver Timing Control
compatible and suitable to remain
permanently in the body. The pen
Digital TIA Integration Ambient Cancellation
is a sterile, single-use, disposable
injector to place the hydrogel at an
approximate depth of 2–6 mm from
the surface of the skin. A handheld Digital TIA
device is placed on the skin over the Resistive DAC
implanted hydrogel. The spotlight in VREF
this instrument uses optical signals
to communicate with the sensor to
receive the O2 data. The data from
the O2 are transmitted to the console RDAC Linearized
for postprocessing and analysis. by DEM

Implantable Deep-Tissue O2 Monitor

A fully wireless, implantable, real-time
deep-tissue O2 monitoring system is
presented in [21]. The monitor oper-
ates using a single ultrasound link for – Digital
N-Bit
INT Signal
both the uplink/downlink data trans- + ADC DOUT
VREF Process
mission and power. A high-voltage I=
RDAC Oversampling
driver excites an external piezo, Gin-band (SAR ADC)
sending ultrasound pulses into the
tissue when the system is in trans-
mit mode. These pulses arrive after
one time of flight. The monitor uses
these pulses for powering up the FIGURE 8:  The architecture of the Mediatek PPG FE with a digital TIA. Adapted from [47].
system and creating a communica- DEM: dynamic element matching; SAR: successive approximation register.

Data
Electrode NFC
Antialiasing

ADC CPU
Inst. ISO 15693
Filter

Amp Reader
Electrode ADC
Circular
Buffer
Temp.
NFC
IR ISO
LED Trans
PD 15693 BLE Host
Driver Z Amp GPIO Interface Interface
RED
Power

FIGURE 9:  A system diagram of Northwestern University’s medical sensor system. Adapted from [20]. ISO: International Organization for
Standardization. Inst: instrumentation; IR: infrared; Temp.: temperature; Trans Z: transimpedance; Amp: amplifier; GPIO: general purpose
input/output.

IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 41

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 and decoded to provide real-time
data. The miniaturized monitor, de­­
monstrated in Figure 11, employs a
lead zirconate–titanate piezo and a
luminescence sensor that consists of
a μLED for optical excitation, a bio-
compatible O2-sensitive ruthenium
(Ru) luminescent sensor, and an in­­
tegrated chip designed in a 65-nm,
low-power CMOS process. The sys-
tem has been tested in an in vitro
experiment. The initial results show
promise. A comparison of the pro-
posed O2 monitor and a commercial
O2 probe is given in Figure 12(c).
Noninvasive Transcutaneous
O2 Monitor
An integrated readout dedicated
for sensing the partial pressure of
transcutaneous O2 is presented in
[22]. The readout IC, designed in a
0.18-μm, 5-V CMOS process, excites
the O2-sensing luminescent film
with a blue LED and measures the
resulting current flowing through
a photodiode. Figure 13 shows the
top-level block diagram. The read-
out IC consists of two power man-
agement blocks, an analog FE (AFE),
and an LED driver block. The system
has two identical power manage-
ment blocks to isolate the power

Spotlight
PD

LED

Wavelength
630 nm

(a) (b)
Wavelength
800 nm

Lumee Oxygen

(c) (d) (e)

20
Baseline Occlusion Recovery
15
[O2] (µM)

10

0
–300 –200 –100 0 100 200 300 400 500
Time Relative to Start of Occlusions (s)
100
Baseline Occlusion Recovery
80
PtcO2 (mmHG)

60

40

20

0
–300 –200 –100 0 100 200 300 400 500
Time Relative to Start of Occlusions (s)
(f)

FIGURE 10:  The Profusa sensor system with (a) a hydrogel implantable sensor, (b) an injector device, (c) a console, and (d) a light source and
PD module. (e) A cross section showing the basic working principle. (f) Data showing the Profusa system detecting changes in the blood O2
status. Adapted from [48] and [49].

42 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 O2-Sensing Film LED
Optical µLED
Holder Thickness = 1.2 mm
Filter
Flex 4.5 mm
Piezo IC Board
3 mm

Volume ~4.5 mm3

Encapsulation

(a) (b)

FIGURE 11:  (a) An exploded view of (b) the implantable O2 sensor designed by University of California, Berkeley. Adapted from [21].

path between the LED driver and

the AFE. The power management Sensor IC
Sensor
blocks consist of 5-V CMOS devices Piezo Vrect
to withstand a wide range of battery φmod Active Rectifier Cstore
Vdc-dc
voltages for regular silicon LEDs and
Voltage Doubler
Modulation

organic LEDs. The AFE consists of

Switch

Power on Reset RO
two stages: a TIA and a variable-gain Clock
Bias and Reference
amplifier (VGA). The purpose of the Clock
LDOs Division
TIA is to sense the current gener-
φref φref
ated by the photodiode and convert ILED
OOK Demod. LED
it into voltage. The VGA provides the Driver
additional tunable gain required to CLK
VOOK φmod
measure low-intensity input signals. POR 10-bit
FSM TDC AFE Vmid
The film’s fluorescence can be Analog
Data φref
PD ILED
measured in terms of either inten-
sity or lifetime, as presented in [39].
The performance of the two tech- (a)
niques was analyzed and compared
1.96 mm
in [38]. The lifetime (decay time) NEOFOX O2 Probe
Wireless Sensor
O2 Concentration (mmHg)

and intensity (amplitude) were mea- 80

sured for different concentrations
of O2, ranging from 0.5 to 500 mm 60
of mercury. Figure 14(a) and (b) con-
1.96 mm

veys the result for both the low and 40

high reflectance, respectively. This
simulates the real-world example of 20
the instrument being used on indi-
viduals with different skin tones. 0
0 10 20 30 40
While both the intensity and the
Time (min)
lifetime are inversely proportional
(b) (c)
to the concentration of O2, which
can be observed from Figure 14(c),
the intensity of the reemitted light FIGURE 12:  (a) A system diagram of an implantable O2 sensor. (b) A micrograph of an SoC
in a 65-nm, low-power-CMOS process. (c) The system response to alternating streams of O2
varies strongly with the differences
and nitrogen. Adapted from [21]. AFE: analog FE; FSM: finite state machine; RO: ring oscillator;
in the optical path. The differences OOK Demod.: on/off keying demodulation; POR: power on reset; Ref.: reference; TDC: time-to-
in the lifetime measurement are digital converter; D-LDO: digital low-dropout regulator; A-LDO: analog low-dropout regulator.

IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 43

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 significantly smaller for the two
reflecting surfaces, as seen in Fig-
ure 14(d), which is an indicator that
this method is less susceptible to
skin color differences.
The performance of the readout
chip was tested on the human body by
placing a fingertip on the sensor head,
as demonstrated in Figure 15(a). The
output was sampled every 5 s. Dur-
ing the first 90 s, O2 values were
measured with normal blood circu-
lation. After that, for the following
90 s, blood circulation was restricted
by wrapping a string around the
finger to create an occlusion. The
average lifetime during normal cir-
culation was 51.7 μs, whereas it was
62.5 μs during the occlusion period.
The measured results are presented
in Figure 15(b).
Discussion
As discussed in the previous section,
emerging fluorescent-based O2 moni-
tors demonstrate promising results.
However, there are many challenges
associated with the design, develop­­
ment, fabrication, and implementation
of such devices. These difficulties
are present in the form of software
and hardware constraints, form fac-
tors, weights, low power require-
ments, battery life, and wireless
operation. The biocompatibility of
encapsulation, water resistance, and
a device’s shape and size all play
vital roles in users’ experiences and
the equipment’s effectiveness. These
emerging instruments should be
small and lightweight to prevent inju-
ries to patients. For externally applied
devices, the effect of materials on
skin integrity is critical to the moni-
tors’ essential requirements of safety.
For any wearable/implantable tech-
nology, power consumption by the
communication system is the main
culprit. Different energy harvesting
schemes will need to be explored
to meet the power demands, as the
presence of a continuous and robust
power supply is the main require-
ment for constant monitoring.
Beyond the Requirements of the
Food and Drug Administration
For any wearable/implantable device
to be considered and evaluated as a
medical-grade instrument, a certain
degree of accuracy is expected, reduc-
ing the rate of false positives and, even
worse, false negatives. According to the
U.S. Food and Drug Administration,

VBATT
VDD VBIASP
VREF
BGR VPCAS
VDD
LDO Bias VBIASN
POR
POR VBIAS1-4
X2
Power Management

EN
VISEN VRAMP
IIND Current Σ VCO
VLED Sense
VSUM RAMPH
SAFE
Clock
Q S RAMPL

+
VREFOSC
Driver Q R
Pt-Porphyrin Film
Oxygen

VDRV –
DRVCTL PWM VREFCOMP
LED Driver
VDIODEP
RCTL
IINP VTIAOP
+ – – + VAFEOP

TIA VGA
IINN VTIAON
– + + –
VAFEON

VDIODEN Analog FE

FIGURE 13:  A block diagram of the readout IC designed by the Worcester Polytechnic Institute Integrated Circuits and Systems Lab [22]. VCO:
voltage-controlled oscillator; PWM: pulsewidth modulation; BGR: bandgap reference; VAFE: output voltage of the analog FE; REFOSC: oscillator
reference voltage; REFCOMP: comparator reference voltage; EN: enable signal.

44 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 ­ edical devices are categorized as
m with stretchable printed antennas
class 1, 2, and 3 depending on the
amount of risk, with class 1 pre-
senting the least danger. While it is
extremely important and necessary
to meet regulatory requirements for
safety and efficacy, designers should
keep in mind the basic needs of the
end user. The monitor should be easy
enough to use that it does not require
the intervention or interpretation
of medically trained personnel. It
should be comfortable to handle
and not cause any additional harm
and discomfort to the patient. Next-
minimizes pulling and skin damage
and small, high-density capacitors through newly developed patch mate-
and compact power transmitters and rial that bonds to the skin using van
receivers [20], [21]. In addition to adhe- der Waals force. Microfluidic channels
sives, materials, in general, that are further reduce the forces needed to
used to attach medical devices to the remove the patch [20].
body will play a key role in creating
comfortable and practical wearables/ Artificial Intelligence
implantables. Researchers at North- In current practice, collecting biosig-
western University have presented a nals from many patients for a cer-
stretchable and flexible substrate that tain amount of time faces multiple
0.6 0.6
AFE Output (V)

AFE Output (V)

generation flexible electronics and 0.4 0.4
PCBs need to be explored to facilitate Increasing Increasing
PO2 PO2
more comfortable devices.
0.2 0.2

Next-Generation Materials
0 0
Past attempts at medical wearables/ 0 25 50 75 100 0 25 50 75 100
implantables have been bulky, with Time (µs) Time (µs)
rigid PCBs embedded in silicon foam (a) (b)
or rubber housings [26], [50]. Medical 70
600
device designers should take advan- Data 1 Data 1
AFE Output (mV)

Fit 1 60
Fit 1

Fall Time (µs)

tage of new flexible PCB technology
500 Data 2 Data 2
and even flexible devices. Organic 50
Fit 2 Fit 2
devices, such as LEDs and PDs, have 40
been demonstrated to provide effective 400
30
FEs for medical sensors with improved
patient compliance [19], [28]. New 300 20
0 200 400 600 0 200 400 600
stretchable and flexible substrates will
Oxygen Partial Pressure (mmHg) Oxygen Partial Pressure (mmHg)
also facilitate more comfortable and
(c) (d)
reliable medical wearables [20]. One
of the significant problems is stability
FIGURE 14:  The fluorescence-based O2 sensor response. Fluorescence decay transients for dif-
with temperature and humidity, which
ferent O2 pressures (PO2) with (a) lower reflectance and (b) higher reflectance optical paths. The
is mainly limited by the encapsulation (c) intensity and (d) lifetime measurements for different O2 concentrations for both cases [38].
of the devices [19], [28]. Forming reli-
able connections between terminals
and flexible substrates is a significant
Normal 75
challenge and needs careful consid-
eration [51]. Researchers at the Geor- 70
gia Institute of Technology present 65
Lifetime (t) [µs]

stretchable copper and gold traces and

flexible connectors that can interface 60
with traditional IC packages [46]. 55
Occlusion
Truly flexible battery cells are an
emerging technology and not yet 50
widely available. There are small, 45 Normal Occlusion
semirigid lithium polymer cells avail-
able, but they cannot withstand much 40
0 50 100 150 200
bending and movement. Additionally, Ribbon Sample Time (s)
interfacing these batteries with a flex- (a) (b)
ible substrate is a challenge, as with
most ridged components. Wireless FIGURE 15:  (a) The test setup for transcutaneous measurements. (b) Transcutaneous O2 mea-
charging offers a possible solution surement on the human body [22].

IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 45

Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
 challenges, such as individual and
regular calibrations. Every human
body is unique; therefore, each
wearable may require individual
adjustments. In addition to this, the
drift in the sensing material through
time requires regular correction.
Long-term signal acquisition is also
susceptible to signal instability and
drift. Such problems may have a sig-
nificant impact on the accuracy of a
device. Having on-sensor deep learn-
ing algorithms can enable a trained
data set that will work as a feedback
system for the robust operation
and accuracy of devices, which will
reduce false negatives and positives.
Integrated deep learning algorithms
on devices may correct human-to-
human variations and drifts in read-
ings due to the device components
and environment, and they may
detect important features in respi-
ratory signals to assist physicians
with providing the highest qual-
ity analysis.
Conclusions
Next-generation blood gas monitors
are essential for the future of medi-
cal care. These new tools will be vital
for treating any diseases and condi-
tions that O2 affects or in which O2 is
affected, including new respiratory
diseases, such as COVID-19, and long-
standing health-care problems, such
as sleep apnea and COPD. Medical
devices and treatment plans that can
be personalized will improve qual-
ity of care for a significant number
of patients. This kind of care is not
possible without remote and continu-
ous monitoring of blood gas content,
especially for respiratory diseases.
In this article, we covered emerg-
ing blood gas monitoring devices
and techniques to create the sensors
and IC structures to transform bulky
benchtop instruments to miniatur-
ized, next-generation biomedical
devices. We also discussed some of
the challenges that engineers face
in developing medical wearables/
implantables and solutions to enable
these revolutionary devices to become
the new standard in medical care.
46 FA L L 2 0 2 0 IEEE SOLID-STATE CIRCUITS MAGAZINE
Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
References
[1] L. Gattinoni et al., “COVID-19 pneumonia:
Different respiratory treatments for differ-
ent phenotypes?” Intensive Care Med., vol.
46, no. 6, pp. 1099–1102, 2020. doi: 10.1007/
s00134-020-06033-2.
[2] R. Levitan. “The infection that’s silently
killing coronavirus patients.” NY Times.
https://www.nytimes.com/2020/04/20/
opinion/sunday/coronav ir us-testing
-pneumonia.html (accessed May 2020).
[3] G. B. Smith, D. R. Prytherch, P. E. Schmidt,
P. I. Featherstone, and P. Meredith, “A re-
ply to: Young C, Beasley R. “The associa-
tion between SpO2 values and mortality–
interpret with caution,” Resuscitation,
vol. 84, no. 2, p. e43, 2013. doi: 10.1016/
j.resuscitation.2012.11.009.
[4] K. Aung, “2018-guideline: Panel recom-
mends maintaining SpO2 at no higher than
96% in most acutely ill hospitalized pa-
tients,” ACP J. Club, vol. 170, no. 6, p. JC26,
2019. doi: 10.7326/ACPJ201903190-026.
[5] M. Folke, L. Cernerud, M. Ekström, and B.
Hök, “Critical review of non-invasive respi-
ratory monitoring in medical care,” Med.
Biol. Eng. Comput., vol. 41, no. 4, pp. 377–
383, 2003. doi: 10.1007/BF02348078.
[6] M. Hernandez-Silveira, K. Wieczorkows-
k i-Rettinger, S. A ng, and A . Burdett,
“Preliminary assessment of the sensi-
umvitals®: A low-cost wireless solution
for patient surveillance in the general
wards,” in Proc. 2015 37th Annu. Int. Conf.
IEEE Engineering Medicine Biology Soci-
ety (EMBC), pp. 4931–4937. doi: 10.1109/
EMBC.2015.7319498.
[7] S. R. Braun, Respiratory Rate and Pattern,
3rd ed. New York: Butterworths, 1990,
pp. 226–230.
[8] J. W. Severinghaus, P. Astrup, and J. Murray,
“Blood gas analysis and critical care medi-
cine,” Amer. J. Respiratory Crit. Care Med.,
vol. 157, no. 4, pp. S114–S122, Apr. 1998. doi:
10.1164/ajrccm.157.4.nhlb1-9.
[9] “Respiratory failure,” National Heart, Lung,
and Blood Institute, Bethesda, MD. Ac-
cessed: Apr. 2020. [Online]. Available: https://
www.nhlbi.nih.gov/health-topics/respiratory
-failure
[10] F. Al-Khalidi, R. Saatchi, D. Burke, H. El-
phick, and S. Tan, “Respiration rate moni-
toring methods: A review,” Pediatric Pul-
monol., vol. 46, no. 6, pp. 523–529, 2011.
doi: 10.1002/ppul.21416.
[11] M. Hernandez-Silveira et al., “Assessment
of the feasibility of an ultra-low power,
wireless digital patch for the continuous
ambulatory monitoring of vital signs,”
BMJ Open, vol. 5, no. 5, p. e006606, 2015.
doi: 10.1136/ bmjopen-2014-006606.
[12] D. Sen, I. Costanzo, and U. Guler, “Contem-
porary and nascent techniques for monitor-
ing of oxygenation as a vital sign,” in Proc.
IEEE Int. Midwest Symp. Circuits Systems,
(MWSCAS), Aug. 2020, pp. 647–650. doi:
10.1109/MWSCAS48704.2020.9184660.
[13] F. Curley, F. Gerard, M. Kevin, G. Leo, M.
Laffey, and G. John, “Mechanical ventila-
tion: Taking its toll on the lung,” Anesthe-
siology, J. Amer. Soc. Anesthesiologists,
vol. 111, no. 4, pp. 701–703, Oct. 2009. doi:
10.1097/01.anes.0000358753.29528.fb.
[14] Electrochemical device for chemical anal-
ysis, by L. Clark. (Nov. 1956) U.S. 2 913
386 A [Online]. Available: https://patents
.google.com/patent/US2913386A/en?q=c
lark+oxygen+electrode&inventor=Clark&
before=priority:19600101&after=priority:
19500101&sort=old
[15] J. Severinghaus and A. Bradley, “Elec-
trodes for blood pO2 and pCO2 determina-
tion,” J. Appl. Physiol., vol. 13, no. 3, pp.
515–520, 1958. doi: 10.1152/jappl.1958.
13.3.515.
[16] J. Severinghaus and Y. Honda, “History of
blood gas analysis. VII. Pulse oximetry,” J.
Clin. Monit., vol. 3, pp. 135–138, Apr. 1987.
doi: 10.1007/BF00858362.
[17] P. Eberhard, “The design, use, and results
of transcutaneous carbon dioxide analy-
sis: Current and future directions,” Anes-
thesia Analgesia, vol. 105, no. 6, pp.
S48–S52, Dec. 2007. doi: 10.1213/01.ane.
0000278642.16117.f8.
[18] “Fitbit fitness tracker.” Accessed on: Feb.
15, 2019. [Online]. Available: https://www
.fitbit.com/home
[19] C. J. Lim, S. Lee, J. H. Kim, H. J. Kil, Y. C.
Kim, and J. W. Park, “Wearable, lumines-
cent oxygen sensor for transcutaneous
oxygen monitoring,” ACS Appl. Mater.
Interfaces, vol. 10, no. 48, pp. 41,026 –
41,034, July 2018. doi: 10.1021/acsami.
8b13276.
[20] H. U. Chung et al., “Binodal, wireless epi-
dermal electronic systems with in-sensor
analytics for neonatal intensive care,”
Science, vol. 363, no. 6430, p. eaau0780,
2019. doi: 10.1126/science.aau0780.
[21] S. Sonmezoglu and M. M. Maharbiz, “34.4
a 4.5mm3 deep-tissue ultrasonic implant-
able luminescence oxygen sensor,” in
Proc. 2020 IEEE Int. Solid-State Circuits
Conf. (ISSCC), pp. 454–456. doi: 10.1109/
ISSCC19947.2020.9062946.
[22] I. Costanzo, D. Sen, and U. Guler, “An inte-
grated readout circuit for a transcutane-
ous oxygen sensing wearable device,” in
Proc. IEEE Custom Integrated Circuits Conf.
(CICC), Mar. 2020, pp. 1–4. doi: 10.1109/
CICC48029.2020.9075881.
[23] “Apple watch,” Apple, Cuper tino, C A ,
2020. [Online]. Available: https://www
.apple.com/apple-watch-series-5/health/
[24] SensiumVitals[textregistered]. Accessed
on: Jan. 31, 2019. [Online]. Available: https://
www.sensium.co.uk/
[25] “MightySat Rx,” Masimo, Irvine, CA, July
2020. Accessed: July 17, 2020. [Online]. Avail-
able: https://www.masimo.com/products/
monitors/spot-check/mightysatrx
[26] S. Song et al., “A 769 µw battery-powered
single-chip SoC with BLE for multi-modal
vital sign monitoring health patches,”
IEEE Trans. Biomed. Circuits Syst., vol. 13,
no. 6, pp. 1506–1517, 2019. doi: 10.1109/
TBCAS.2019.2945114.
[27] J. W. Severinghaus, “Career perspective:
John W. Severinghaus,” Extreme Physiol.
Med., vol. 2, Oct. 2013, Art no. 29. doi:
10.1186/2046-7648-2-29.
[28] C. M. Lochner, Y. Khan, A. Pierre, and A. C.
Arias, “All-organic optoelectronic sensor
for pulse oximetry,” Nature Commun., vol.
5, Dec. 2014, Art no. 5745. doi: 10.1038/
ncomms6745.
[29] P. E. Bickler, J. R. Feiner, and J. W. Sever-
inghaus, “Effects of skin pigmentation on
pulse oximeter accuracy at low saturation,”
Anesthesiology, vol. 102, no. 4, pp. 715–
719, Apr. 2005. doi: 10.1097/00000542-
200504000-00004. [Online]. Available:
https://anesthesiology.pubs.asahq.org/
article.aspx?articleid=1942319
[30] “The effects of dark skin pigmentation
and low saturation in oximetry,” Nonin,
Plymouth, MN, Aug. 2020. Accessed: Aug.
4, 2020. [Online]. Available: https://www
.nonin.com/resource/effects- of-sk in
-pigmentation-in-oximetry
[31] E. D. Chan, M. M. Chan, and M. M. Chan,
“Pulse oximetry: Understanding its ba-
sic principles facilitates appreciation of
its limitations,” Respiratory Med., vol.
107, no. 6, pp. 789–799, June 2013. doi:
10.1016/j.rmed.2013.02.004.
 [32] S. DeMeulenaere, “Pulse oximetry: Uses
and limitations,” J. Nurse Practitioners,
vol. 3, no. 5, pp. 312–317, May 2007. doi:
10.1016/j.nurpra.2007.02.021.
[33] W. M. Schramm, A. Bartunek, and H. Gilly,
“Effect of local limb temperature on pulse
oximetry and the Plethysmographic pulse
wave,” Int. J. Clin. Monit. Comput., vol. 14,
no. 1, pp. 17–22, Feb. 1997. doi: 10.1007/
BF03356574.
[34] S. J. Barker and N. K. Shah, “Effects of motion
on the performance of pulse oximeters in
volunteers,” Anesthesiology, vol. 85, no. 4, pp.
774–781, Oct. 1996. doi: 10.1097/00000542-
199610000-00012. [Online]. Available: https://
anesthesiology.pubs.asahq.org/article
.aspx?articleid=1948423
[35] Y.-s. Yan, C. C. Poon, and Y.-t. Zhang, “Re-
duction of motion artifact in pulse oxim-
etry by smoothed pseudo Wigner-Ville dis-
tribution,” J. Neuroeng. Rehab., vol. 2, no.
1, p. 3, 2005. doi: 10.1186/1743-0003-2-3.
[36] P. J. Chacon et al., “A wearable pulse ox-
imeter with wireless communication and
motion artifact tailoring for continuous
use,” IEEE Trans. Biomed. Eng., vol. 66,
no. 6, pp. 1505–1513, 2019. doi: 10.1109/
TBME.2018.2874885.
[37] C. F. Poets. “Pulse oximetry vs. transcuta-
neous monitoring in neonates: Practi-
cal aspects.” acutecaretesting.org, Oct.
2003. https://acutecaretesting.org/en/
articles/pulse-oximetry-vs-transcutaneous
-monitoring-in-neonates-practical-aspects
(accessed Mar. 2019).
[38] I. Costanzo, D. Sen, and U. Guler, “Fluores-
cent intensity and lifetime measurement
of platinum-porphyrin film for determin-
ing the sensitivity of transcutaneous oxy-
gen sensor,” in Proc. IEEE Int. Symp. Cir-
cuits Systems (ISCAS), May 2020, pp. 1–4.
[39] I. Costanzo, D. Sen, and U. Guler, “A pro-
totype towards a transcutaneous oxygen
sensing wearable,” in Proc. IEEE Biomedi-
cal Circuits Systems Conf. (BioCAS), Oct.
2019, pp. 1–4. doi: 10.1109/BIOCAS.2019.
8919229.
[40] J. Larsen, N. Linnet, and P. Vesterager,
“Transcutaneous devices for the measure-
ments of pO2 and pCO2. State-of-the-art, es-
pecially emphasizing a pCO2 sensor based
on a solid-state glass pH sensor,” Ann. Biol.
Clin., vol. 51, nos. 10–11, pp. 899–902,
1993. [Online]. Available: https://pubmed
.ncbi.nlm.nih.gov/8210067
[41] W. van Weteringen et al., “Novel transcu-
taneous sensor combining optical tcPO2
and electrochemical tcPCO2 monitoring
with reflectance pulse oximetry,” Med.
Biol. Eng. Comput., vol. 58, no. 2, pp. 239–
247, Feb. 2020. doi: 10.1007/s11517-019-
02067-x.
[42] M. J. Sinclair, R. Ann Hart, H. M. Pope,
and E. J. M. Campbell, “The use of the
henderson-hasselbalch equation in rou-
tine medical practice,” Clin. Chimica Acta,
vol. 19, no. 1, pp. 63–69, Jan. 1968. doi:
10.1016/0009-8981(68)90189-7.
[43] D. C. Hutchison, G. Rocca, and D. Hon-
eybourne, “Estimation of arterial oxygen
tension in adult subjects using a transcu-
taneous electrode,” Thorax, vol. 36, no.
6, pp. 473–477, June 1981. doi: 10.1136/
thx.36.6.473.
[44] S. Kesten, K. Chapman, and A. Rebuck,
“ Re sp on s e c h a r ac te r ist ic s of a du a l
transcutaneous oxygen/carbon dioxide
monitoring system,” Chest, vol. 99, no. 5,
pp. 1211–1215, June 1991. doi: 10.1378/
chest.99.5.1211.
[45] M. Konijnenburg et al., “22.1 a 769µw bat-
tery-powered single-chip SoC with BLE for
multi-modal vital sign health patches,”
in Proc. 2019 IEEE Int. Solid-State Circuits
IEEE SOLID-STATE CIRCUITS MAGAZINE FA L L 2 0 2 0 47
Authorized licensed use limited to: Birla Institute of Technology & Science. Downloaded on April 09,2021 at 05:04:05 UTC from IEEE Xplore. Restrictions apply.
Conf. (ISSCC), pp. 360–362. doi: 10.1109/
ISSCC.2019.8662520.
[46] H. Kim et al., “Fully integrated, stretchable,
wireless skin-conformal bioelectronics
for continuous stress monitoring in daily
life,” Adv. Sci., vol. 7, no. 15, p. 2,000,810,
2020. doi: 10.1002/advs.202000810.
[Online]. Available: https://onlinelibrary.
w i l e y. c o m /d o i / a b s / 10 .10 0 2 / a d v s .
202000810
[47] Y. Shu et al., “26.1 a 4.5mm2 multimodal
biosensing SoC for PPG, ECG, BIOZ and
GSR acquisition in consumer wearable de-
vices,” in Proc. 2020 IEEE Int. Solid- State
Circuits Conf. (ISSCC), pp. 400–402. doi:
10.1109/ISSCC19947.2020.9063112.
[48] M. Montero-Baker, A. G. Schwindt, and T.
Bisdas, “Potential utility of tissue oxygen
sensors in perfusion monitoring,” Endovas-
cular Today, vol. 17, no. 5, pp. 60–64, 2018.
[49] S. C. Kanick, P. A. Schneider, B. Klitzman,
N. A. Wisniewski, and K. Rebrin, “Continu-
ous monitoring of interstitial tissue oxy-
gen using subcutaneous oxygen microsen-
sors: In vivo characterization in healthy
volunteers,” Microvascular Res., vol. 124,
pp. 6–18, July 2019. doi: 10.1016/j.mvr.
2019.02.002.
[50] R. G. Haahr, S. Duun, E. V. Thomsen, K.
Hoppe, and J. Branebjerg, “A wearable
“electronic patch” for wireless continu-
ous monitoring of chronically diseased
patients,” in Proc. 2008 5th Int. Summer
School Symp. Medical Devices Biosensors,
pp. 66–70. doi: 10.1109/ISSMDBS.2008.
4575018.
[51] P. Lall, H. Jang, B. Leever, and S. Miller,
“Folding-reliability of flexible electron-
ics in wearable applications,” in Proc.
ASME 2019 Int. Technical Conf. Exhibition
Packaging Integration Electronic Pho -
tonic Microsystems. doi: 10.1115/IPACK
2019-6584.
About the Authors
Ulkuhan Guler (uguler@wpi.edu) rece­
ived her B.Sc. degree in electronics and
telecommunication engineering from
Istanbul Technical University, Turkey;
her M.E degree in electronics engineer-
ing from the University of Tokyo; and
her Ph.D. degree from Bogazici Uni-
versity, Istanbul. She worked at the
National Research Institute of Electron-
ics and Cryptology, Gebze, Turkey,
from 2006 until 2015 as a principal
design engineer. In 2015, she joined
the Georgia Institute of Technology
as a postdoctoral research fellow. She
is currently an assistant professor at
Worcester Polytechnic Institute, Massa-
chusetts. Her research interest is ana-
log/mixed-signal IC design for sensing
interfaces, bioelectronics, and security
for health-care applications. She is a
Senior Member of IEEE and serves as a
reviewer for IEEE Journal of Solid-State
Circuits and on the technical program
committee of the IEEE Custom Inte-
grated Circuits Conference.
Ian Costanzo (imcostanzo@wpi
.edu) received his B.Sc. degree i n
mechanical engineering, with a
minor in electrical engineering from
Worcester Polytechnic Institute (WPI),
Massachusetts, in 2015. He received
his M.S. degree in electrical engineer-
ing in 2017, also from WPI. He is cur-
rently a Ph.D. candidate at the WPI
New England Center for Analog and
Mixed-Signal IC Design and the WPI
Integrated Circuits and Systems Lab.
His research interests cover a broad
range of circuits and systems, from
kilowatt radio-frequency (RF) subsys-
tems to microwatt data converters.
While completing his M.S. degree, he
worked on solid-state, high-power RF-
matching networks and RF amplifiers
for semiconductor processing appli-
cations. His Ph.D. research focuses
on analog and mixed-signal design
for a wearable wireless sensor patch
for monitoring respiratory functions
in premature infants. He is a Student
Member of IEEE.
Devdip Sen (dsen@wpi.edu) recei­­
ved his B.E. degree in electronics
engineering from the University of
Mumbai, India, in 2015 and his M.S.
degree in electrical and computer
engineering from Worcester Polytech-
nic Institute (WPI), Massachusetts, in
2017. He is currently a Ph.D. candidate
at the WPI New England Center for Ana-
log and Mixed-Signal IC Design and the
WPI Integrated Circuits and Systems
Lab. His research interests include bio-
medical instrumentation; sensors and
systems; low-power analog/mixed-
signal circuits and systems; wireless,
autonomously powered embedded
systems for biomedical applications;
and low-power data converters. His
Ph.D. research includes the develop-
ment of wearable, wireless sensors for
monitoring respiratory functions in
premature infants and wearable, wire-
less alert systems that would prevent
painful pressure ulcers (bedsores). He
serves as a reviewer for various IEEE
conferences, the ASEE student divi-
sion, and IEEE Transactions on Bio-
medical Circuits and Systems. He is a
Student Member of IEEE.