Study of Stress Levels in Various Materials in Total Knee Replacements Under Static Condition
Development of a bionanodevice for detecting stress levels
Transcript of Development of a bionanodevice for detecting stress levels
Development of a bionanodevice for detecting stress levels
S Nomura1,3
, S Handri1, and H Honda
2,3
1 Top Runner Incubation Center for Academia-Industry Fusion, Nagaoka University of
Technology, 1603-1 Kamitomioka, Nagaoka 940-2188, Japan 2 Department of Bioengineering, Nagaoka University of Technology, 1603-1
Kamitomioka, Nagaoka 940-2188, Japan
Abstract. Recent advances in molecular analysis techniques have enabled scientists to assess
the tiny amounts of biochemical substances secreted in our bodies. This has revealed that the
levels of various secretory hormones and immune substances vary sensitively with the mental
state of a person. Such hormones and immune substances exhibit transient increases with
various psychological stressors. They thus have the potential to be used as a novel biometric
for monitoring stress. Biomarkers that occur in saliva can be monitored non-invasively and are
thus potentially useful as practical indicators of mental stress. Stress biomarkers are considered
to be released into the blood stream or other secretory fluids by physiological stress reactions.
Stress biomarkers are expected to be detectable in sweat and other humoral fluids that are
exuded from the skin surface. Based on this, we have developed a bionanodevice for detecting
stress by capturing stress biomarkers on the skin surface in a non-invasive manner. A prototype
bionanodevice is described in which a motor protein is introduced for molecular handling.
1. Introduction
Mental health problems represent an acute global problem. They are not just problems of individuals
but they also represent a social problem. The International Labor Organization reported various effects
of mental health problems on society; for example, it estimated the financial cost of mental health
problems in the European Union to be about 3 to 4 % of the GNP [1]. However, it is generally difficult
for individuals to monitor their own mental stress levels making it hard to manage mental stress
unaided. It is thus important to devise a practical methodology for evaluating, managing, and
controlling mental stress.
Recent advances in molecular analysis techniques allow scientists to monitor tiny amounts of
substances contained in human secretory fluids. The levels of some hormones and immune substances
in the body have been found to vary in response to a person’s mental state. For example, salivary
immunoglobulin A (IgA) transiently increases in response to short-term psychological stressors such as
mental arithmetic tasks, stroop tasks, and academic presentations [2]. Therefore, the levels of such
substances are expected to be useful as novel biometrics for stress. Several such potential stress
biomarkers have been reported in behavioural medicine and psychophysiological studies [3].
Moreover, since these substances are secreted into the blood stream or external/internal secretory
fluids through activation of physiological stress reactions, they are expected to be determinable by
analyzing sweat and other humoral fluids that are exuded from the skin. This gave us the idea of
3 Corresponding authors. E-mail: [email protected], [email protected]
International Symposium on Global Multidisciplinary Engineering 2011 (S-GME2011) IOP PublishingIOP Conf. Series: Materials Science and Engineering 21 (2011) 012029 doi:10.1088/1757-899X/21/1/012029
Published under licence by IOP Publishing Ltd 1
developing a bionanodevice for detecting stress that obtains tiny amounts of stress biomarkers from
the skin surface in a non-invasive manner.
In this paper, we briefly review previous stress biomarker studies; in particular, we consider the
results of our past studies on potential stress biomarkers. We also describe a prototype bionanodevice
that employs a motor protein for molecular handling.
2. Stress biomarkers: background and example
2.1. Physiological stress reaction pathways
A wide range of secretory substances have been reported to change their levels in response to certain
stressors. These substances are considered as potential biomarkers for stress. Seven biomarkers are
currently used as stress biomarkers; they include hormones, immune substances, proteins, and
enzymes and are the following: immunoglobulin A (IgA), cortisol, chromogranin A (CgA), alpha
amylase, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S), and
testosterone (TE) [2].
The reaction mechanisms of these substances in response to mental stress are considered in relation
to the human physiological stress reaction pathways. The two internal stress reaction pathways are the
hypothalamus-pituitary-adrenal (HPA) and sympatho-adrenal-medullary (SAM) systems [4] (Figure
1). The above seven biomarkers are considered to be released into the blood or other secretory fluids
and thus reflect the activation of one of the two reaction pathways: IgA, CgA, and amylase are
considered to reflect SAM activation, while cortisol, DHEA, and DHEA-S are considered to reflect
HPA activation.
Stress biomarker studies investigate secretory hormones and immune substances that accurately
reflect activation of the HPA or SAM system so that they can be used as objective indicators of mental
stress levels. Below, two important biomarkers in this field, IgA and cortisol, are described.
Figure 1. Stress reaction pathway and a method for detecting stress levels using a
bionanodevice.
Pituitary
ANS Center
Cerebral Cortex
Adrenal cortex
Adrenal Medulla
Hypothalamus
DHEA Cortisol
N, NE
IgA Amylase
Stressor
SA
M s
ystemH
PA
System
Bio-nanodevicetoward stress detection
Specimen collectionOn-site analysis
International Symposium on Global Multidisciplinary Engineering 2011 (S-GME2011) IOP PublishingIOP Conf. Series: Materials Science and Engineering 21 (2011) 012029 doi:10.1088/1757-899X/21/1/012029
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2.2. Possible stress biomarkers: immunoglobulin A (IgA) and cortisol
Immunoglobulin A (IgA) is one of the most important substances in the human immune system. IgA
functions non-specifically and thus plays a very important role in our health (e.g., inhibiting
pathogenic viruses from entering epithelial cells). Thus, salivary IgA is frequently referred to as our
first line of defense against influenza or other respiratory tract infections. Behavioral medicine studies
conducted in the 1970s revealed that salivary IgA levels vary in response to various psychological
factors, including desirable and undesirable daily events, daily hassles, negative and positive moods,
academic stress, stressful short-term cognitive tasks, and relaxation [5]. We observed temporarily
elevated IgA levels in university students who were studying for their final examinations [6] (Figure
2).
(a)
(b)
Figure 2. (a) Profile of mood states (POMS; a psychological scale) and (b) IgA
concentrations of undergraduate university students before (day I) and after (day
II) their final examinations (from [5]). Within-subjects design (n = 20) was
employed. POMS consist of six mood factors: tensionanxiety (TA),
depressiondejection (D), angerhostility (AH), vigor (V), fatigue (F), and
confusion (C)
0
5
10
15
20
25
30
T-A D A-H V F C
Day I
Day II
Sco
res
of
PO
MS
***
**
*****
**
*** p<0.001
** p<0.01
0
50
100
150
200
250
Day I Day II
IgA
Co
nce
ntr
atio
n [μ
g/m
L] ***
*** p <0.001
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Cortisol is the most potent glucocorticoid produced. It is secreted by the adrenal cortex. It plays an
important role in that it maintains adequate blood glucose levels. Cortisol is considered to be released
into the blood stream by activation of the HPA system, so it is a potential stress biomarker [4]. A
transient increase in salivary cortisol has been observed in response to short-term stressors such as
mental arithmetic, stroop tasks, and oral presentations [4,7]. Moreover, the level of cortisol released
immediately after waking has recently been reported to reflect chronic stress levels [8]. This was
confirmed by an experiment we conducted that demonstrated that performing mild exercise prior to
going to bed alleviates hypersecretion of cortisol after awakening (Figure 3).
Although there must be many potential mediators that affect the secretion of these stress biomarkers,
(e.g., sex, age, personality), this method promises to provide a completely new methodology for
objectively estimating stress levels.
Figure 3. Cortisol awakening response: the salivary cortisol
concentration immediately before going to bed (tn), immediately
after waking (t0), 30 min after waking (t15), and 45 min after
waking (t45). Within-subject design (n = 8) was employed. The
“Exercise” group performed mild exercise about an hour before
going to bed.
3. Bionanodevice for detecting human stress — a developing idea
The ultimate goal of the above-mentioned stress biomarker studies is on-site assessment of human
stress. As mentioned above, stress biomarkers can be released into the blood or saliva via activation of
the two physiological stress reaction pathways (i.e., HPA and SAM). Stress biomarkers are also
expected to be determinable by analyzing sweat and other humoral fluids that are exuded from the skin.
Therefore, an on-site stress detection device needs to be compact, integrated, sensitive, and non-
invasive.
A motor protein-powered device is a possible means for achieving this challenging goal. Motor
proteins perform nanoscale mechanical movements by using chemical energy generated by hydrolysis
of ATP. Various nanoscale platforms using motor proteins have been proposed [9]. We are currently
focusing on a molecular transport system that harnesses the actinmyosin interaction (Figure 4). The
-1.50
-1.00
-0.50
0.00
0.50
1.00
1.50
tn t0 t30 t45
Exercise
Control
Co
rtis
ol
Co
nce
ntr
atio
n(z
-sco
re) *
**
* p<.05, ** p<.01 vs tn
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actinmyosin interaction typically occurs in muscles; it is used to generate the extremely powerful
contractions of muscles. The platform shown in Figure 4 harnesses this motor protein interaction.
Since the actin filaments are attached to myosin, which is fixed to the substrate, the actin filaments can
act as a shuttle for transporting an attached cargo (antibodies of the target stress biomarker, in our
case). The spatial configuration of the substrate on which myosin or another motor protein are fixed is
critical for controlling the molecular transport system and thus for constructing an on-chip device.
Tracks are formed in poly(methylmethacrylate) or another substrate. These tracks constrain the actin
filaments while allowing them to move smoothly within the tracks [10].
Although these concepts are currently being demonstrated merely as proof of principle, they
promise to result in molecular handling technology for achieving on-site assessment of stress levels.
Figure 4. Actinmyosin platform for molecular transport system.
4. Conclusion
This paper reviewed previous stress biomarker studies including our experimental results and it
describes the concepts behind a bionanodevice for on-site assessment of stress levels. As mentioned
above, the problem of mental stress is currently a global crisis. Moreover, the difficulty of individuals
monitoring and managing their stress levels unaided makes mental stress more serious. Future studies
will contribute stress management research through the development of a means for objectively
measuring stress levels.
Acknowledgement
This study was financially supported by Program for Developing the Supporting System for Global
Multidisciplinary Engineering Establishment, Ministry of Education, Culture, Sports, Science and
Technology, Japan.
References
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Organization. Retrieved August 1, 2009, from http://ilo.org
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[3] Ader, R., Felten, L. & Cohen, N. (Eds.) (2001) Psychoneruoimmunology. 3rd ed. Academic Press.
International Symposium on Global Multidisciplinary Engineering 2011 (S-GME2011) IOP PublishingIOP Conf. Series: Materials Science and Engineering 21 (2011) 012029 doi:10.1088/1757-899X/21/1/012029
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[4] Kirschbaum, C & Hellhammer, D.H. (1994). Salivary cortisol in psychoneuroendocrine research:
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