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A D’Amico1
*, M Santonico2
, G Pennazza2
, Y Cavalieri3
, G Farullo3
and Enrico Finazzi Agrò4
1
Department of Electronic Engineering -University of Rome “Tor Vergata” -Via del Politecnico 1,00133, Roma
2
Unit of Electronics for Sensor Systems-Department of Engineering-University of Campus Bio-Medico di Roma-Via Alvaro del Portillo, 21-00128, Roma
3
Urology Specialization Medicine-University of Rome “Tor Vergata”
4
Department of Surgical and Experimental Medicine-University of Rome “Tor Vergata”
*Corresponding author: A D’Amico, Department of Electronic Engineering -University of Rome “Tor Vergata” -Via del Politecnico 1,00133, Roma
Submission: November 13, 2017; Published: February 22, 2018
A Sensor Multiplatform for Non Invasive
Diagnosis of Prostate Cancer
Introduction
Prostate cancer (PCa) is the most common tumor among
male solid tumors [1]. Diagnosis of PCa is based on digital rectal
examination (DRE), prostate-specific antigen (PSA) blood test, and
transrectal ultrasound-guided (TRUS) biopsy of the prostate [2].
Screening for early detection of PCa represents one of the most
debated topics in scientific literature [3]. In the last decades, the
use of PSA as the standard screening method in population has led
to a reduction in advanced disease at diagnosis and PCa-related
mortality but also to a large increase in the number of unnecessary
prostate biopsies [4]. Serum level of PSA also raises in other
prostate’s diseases, as BPH or prostatitis [5], implicating several
limits in term of sensibility and specificity. It is indeed estimated
that 15% of men with normal serum level of PSA are afflicted with
PCa, which is high grade in 15% of cases [6]. On the other hand,
this lack of specificity has been associated with a frequent detection
of low-risk localized disease (“overdiagnosis”), that is tumors that
would not have caused clinical consequences during patients
lifetime, with the potential side effects and high health care costs of
the consequent unnecessary treatment (“overtreatment”) [4]. The
introduction in clinical practice of new non-invasive techniques
for detection of significant disease would help us to reduce the
number of unnecessary prostate biopsies and the over diagnosis
and overtreatment of Prostate Cancer.
Mini Review
1/3Copyright © All rights are reserved by A D’Amico.
Volume 1 - Issue - 2
Abstract
This work underlines the utility of a multiplatform based on the use of both artificial olfaction and taste systems that show the ability to perform
both gas and bio liquid chemical imaging. Preliminary results related to the investigation of prostate cancer suggest that high performance levels with
diagnostic and screening purposes can be reached with non invasive experimental procedures.
Technique Description
Figure 1: Overview of the measure chain used with the different approaches (volatile headspace analysis on-line and off-line,
liquid analysis).
Significances of
Bioengineering & BiosciencesC CRIMSON PUBLISHERS
Wings to the Research
ISSN 2637-8078
Significances Bioeng Biosci Copyright © A D’Amico
2/3How to cite this article: A D’Amico, M Santonico, G Pennazza, Y Cavalieri, G Farullo. A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer.
Significances Bioeng Biosci. 1(2). SBB.000509.2018. DOI: 10.31031/SBB.2018.01.000509
Volume 1 - Issue - 2
Along this direction different methods have been developed
and tested for a non invasive diagnostic procedure and preliminary
results suggest that a satisfactory efficiency can be achieved for a
first diagnosis or screening activity.
The basic idea is to analyse the VOC head space of urine
samples from the view point of both olfaction and taste and utilize
four strictly related techniques constituting a useful platform for an
almost complete collection of chemical data from the urines.
The four approaches for the measurements of the urine head
space (HS) characteristics are the following:
I.	 Direct measurements of the urine head space through an
electronic nose (EN) optimized for the purpose;
II.	 Use of a system, called Tenax, to store the VOCs which will
be analysed in a second moment by an EN;
III.	 Use of the volatile compounds of the (HS) to activate an
electronic tongue(ET) in suitable liquids;
IV.	 Direct analysis of the urine head space by an (ET).
In Figure 1 the different techniques are schematically shown.
The first approach considers the application of an EN to the
urine head space in order to build, through a chemical image of it,
the possibility to compare healthy and diseased individuals.
The possibility to obtain a chemical image from urine is
confirmed by several works in this field [7,8]. The first evidences
show that the headspace of biological fluids is typical of certain
pathologies. An important aspect to take into account is the
presence of simultaneous influence of other factors that can reduce
the predictive power of the technique. One of these is the sampling
technique used to measure the urine. In some preliminary studies
the headspace has been measured within two hours and the
methods did not permit to apply the technique in a multicentre
study. This aspect has required the development of dedicated and
more efficient sampling protocols. In particular the possibility
to store VOCs could be a valid approach. In parallel a second
component for the platform has been tested.
It is represented by the VOCs analysis technique which uses
a Tenax tube as a storing system for the gaseous head space. One
of the main advantages is represented by the possibility of non
contaminant gas transportation. In fact the storing action can be
done even many days before the moment where the measurement
by an EN of the conserved gas is done. Another significant advantage
of this technique is the fact that the increase of the adsorbing time
produces a chemical amplification very useful when certain VOCs
are present at very low concentration (ppb or lower).
Athirdfeatureofthisapproachconcernstheuseofatemperature
differentiated desorption(TDD) which can allow the VOCs output
at different temperature intervals which are responsible of the
selection of desorbed VOCs. TDD is proved to be very useful for a
better analysis with the EN due to the fact that in this way sensors
constituting the EN are not charged simultaneously by all the
adsorbed chemicals.
Figure 2: Typical response fingerprint registered for the liquid (left) and gas (right) composition of a urine sample as output of
the sensor system.
The third component of the platform is the electronic tongue
(ET) which can perform chemical imaging of water or other liquids
when they are contaminated by additives which can be liquid or
gaseous or even soluble particles. In our case the urine head space
sample is fed into the reference liquid where it releases some
substances that are representative of the kind of urine under test.
In the first experiments a voltammetric sensor has been used. The
system composed of a dedicated electronic interface to detect small
signals with an optimized S/N ratio is the last version developed at
University Campus Bio-Medico di Roma [9]. The peculiarity of this
sensor system is the possibility to build a chemical image directly
from liquids. Providing different potentials to the electrodes
3/3How to cite this article: A D’Amico, M Santonico, G Pennazza, Y Cavalieri, G Farullo. A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer.
Significances Bioeng Biosci. 1(2). SBB.000509.2018. DOI: 10.31031/SBB.2018.01.000509
Significances Bioeng Biosci Copyright © A D’Amico
Volume 1 - Issue - 2
immersed in the solution allows to detect small changes of current
due to the chemical features of the sample. Each current response
permits to built a specific fingerprint of the samples as the one
provided by the EN for the headspace. In the Figure 2 a typical urine
fingerprint is shown.
The fourth component concerns the direct use of the (ET) to
perform chemical imaging of the liquid sample; in this case it is
possible to detect other useful features able to contribute to the
performance increase of the global platform characteristics. It is
worth pointing out that the urine is only one of the possible biologic
liquid that can be advantageously analysed by the diagnostic
platform.
The different techniques described above, can be applied
individually or jointly. In each case the number of sensors could
be very high. The obtained fingerprints are based on non-selective
sensors. This is valid both for headspace sensors and liquid
sensors. All sensor responses can be analysed using multivariate
approaches distinguishing in unsupervised and supervised
technique. In the first case it is possible to obtain information about
the macroscopic behaviours of data and their correlation with the
pathologies considered in the study. These analyses are performed
taking into account the standard deviation distribution of the data,
elaborating for example a Principal Component Analysis (PCA)
model. A different approach can be used when the sensors or the
sensor systems are calibrated to specific substances. In this case a
model based on a supervised approach (e.g. Partial least square–
Discriminant Analysis) can be utilized and validated to predict the
concentration of a specific compound both in liquid and gas phase.
Conclusions
Purpose of this brief note on the prostate cancer detection,
which does represent but only one of the possible examples that
strongly impact our society, is to underline the importance of the
pluridisciplinary approach which is more than necessary when
an effective diagnostic method has to be tested for its practical
utilization in a screening context. Medical people and engineers
more and more should learn how to melt their respective cultures
in common objectives especially those concerning the people
health. Here we have considered a platform of techniques whose
destiny is certainly that to play a significant role in those particular
moments that deal with a prompt and non invasive diagnosis. It is
worth pointing out that the platform here introduced can be easily
utilized by medical people due to the friendly approach considered
in the design phase of the measurement systems.
References
1.	 American Cancer Society. Cancer facts & figures 2016.
2.	 Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, et al. (2014) EAU
guidelines on prostate cancer. part 1: screening, diagnosis, and local
treatment with curative intent-update 2013. Eur Urol 65(1): 124-137.
3.	 Loeb S (2014) Guideline of guidelines: prostate cancer screening. BJUI
114(3): 323-325.
4.	 Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, et al. (2014)
Overdiagnosis and overtreatment of prostate cancer. Eur Urol 65(6):
1046-1055.
5.	 Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, et al. (1994)
Comparison of digital rectal examination and serum prostate specific
antigen in the early detection of prostate cancer: results of a multicenter
clinical trial of 6,630 men. J Urol 151(5): 1283-1290.
6.	 Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al.
(2004) Prevalence of prostate cancer among men with a prostate-
specific antigen level < or =4.0 ng per milliliter. N Engl J Med 350(22):
2239-2246.
7.	 Asimakopoulos AD, Del Fabbro D, Miano R, Santonico M, Capuano R,
et al. (2014) Prostate cancer diagnosis through electronic nose in the
urine headspace setting: a pilot study. Prostate cancer and prostatic
diseases 17(2): 206-211.
8.	 Bernabei M, Pennazzaa G, Santonicoa M, Corsi C, Roscioni C, et al. (2008)
A preliminary study on the possibility to diagnose urinary tract cancers
by an electronic nose. Sensors and Actuators B: Chemical 131(1): 1-4.
9.	 Santonico M, Pennazza G, Grasso S, D’Amico A, Bizzarri M (2013) Design
and test of a biosensor-based multisensorial system: A proof of concept
study. Sensors 13(12): 16625-16640.
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Crimson Publishers -A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer

  • 1. A D’Amico1 *, M Santonico2 , G Pennazza2 , Y Cavalieri3 , G Farullo3 and Enrico Finazzi Agrò4 1 Department of Electronic Engineering -University of Rome “Tor Vergata” -Via del Politecnico 1,00133, Roma 2 Unit of Electronics for Sensor Systems-Department of Engineering-University of Campus Bio-Medico di Roma-Via Alvaro del Portillo, 21-00128, Roma 3 Urology Specialization Medicine-University of Rome “Tor Vergata” 4 Department of Surgical and Experimental Medicine-University of Rome “Tor Vergata” *Corresponding author: A D’Amico, Department of Electronic Engineering -University of Rome “Tor Vergata” -Via del Politecnico 1,00133, Roma Submission: November 13, 2017; Published: February 22, 2018 A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer Introduction Prostate cancer (PCa) is the most common tumor among male solid tumors [1]. Diagnosis of PCa is based on digital rectal examination (DRE), prostate-specific antigen (PSA) blood test, and transrectal ultrasound-guided (TRUS) biopsy of the prostate [2]. Screening for early detection of PCa represents one of the most debated topics in scientific literature [3]. In the last decades, the use of PSA as the standard screening method in population has led to a reduction in advanced disease at diagnosis and PCa-related mortality but also to a large increase in the number of unnecessary prostate biopsies [4]. Serum level of PSA also raises in other prostate’s diseases, as BPH or prostatitis [5], implicating several limits in term of sensibility and specificity. It is indeed estimated that 15% of men with normal serum level of PSA are afflicted with PCa, which is high grade in 15% of cases [6]. On the other hand, this lack of specificity has been associated with a frequent detection of low-risk localized disease (“overdiagnosis”), that is tumors that would not have caused clinical consequences during patients lifetime, with the potential side effects and high health care costs of the consequent unnecessary treatment (“overtreatment”) [4]. The introduction in clinical practice of new non-invasive techniques for detection of significant disease would help us to reduce the number of unnecessary prostate biopsies and the over diagnosis and overtreatment of Prostate Cancer. Mini Review 1/3Copyright © All rights are reserved by A D’Amico. Volume 1 - Issue - 2 Abstract This work underlines the utility of a multiplatform based on the use of both artificial olfaction and taste systems that show the ability to perform both gas and bio liquid chemical imaging. Preliminary results related to the investigation of prostate cancer suggest that high performance levels with diagnostic and screening purposes can be reached with non invasive experimental procedures. Technique Description Figure 1: Overview of the measure chain used with the different approaches (volatile headspace analysis on-line and off-line, liquid analysis). Significances of Bioengineering & BiosciencesC CRIMSON PUBLISHERS Wings to the Research ISSN 2637-8078
  • 2. Significances Bioeng Biosci Copyright © A D’Amico 2/3How to cite this article: A D’Amico, M Santonico, G Pennazza, Y Cavalieri, G Farullo. A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer. Significances Bioeng Biosci. 1(2). SBB.000509.2018. DOI: 10.31031/SBB.2018.01.000509 Volume 1 - Issue - 2 Along this direction different methods have been developed and tested for a non invasive diagnostic procedure and preliminary results suggest that a satisfactory efficiency can be achieved for a first diagnosis or screening activity. The basic idea is to analyse the VOC head space of urine samples from the view point of both olfaction and taste and utilize four strictly related techniques constituting a useful platform for an almost complete collection of chemical data from the urines. The four approaches for the measurements of the urine head space (HS) characteristics are the following: I. Direct measurements of the urine head space through an electronic nose (EN) optimized for the purpose; II. Use of a system, called Tenax, to store the VOCs which will be analysed in a second moment by an EN; III. Use of the volatile compounds of the (HS) to activate an electronic tongue(ET) in suitable liquids; IV. Direct analysis of the urine head space by an (ET). In Figure 1 the different techniques are schematically shown. The first approach considers the application of an EN to the urine head space in order to build, through a chemical image of it, the possibility to compare healthy and diseased individuals. The possibility to obtain a chemical image from urine is confirmed by several works in this field [7,8]. The first evidences show that the headspace of biological fluids is typical of certain pathologies. An important aspect to take into account is the presence of simultaneous influence of other factors that can reduce the predictive power of the technique. One of these is the sampling technique used to measure the urine. In some preliminary studies the headspace has been measured within two hours and the methods did not permit to apply the technique in a multicentre study. This aspect has required the development of dedicated and more efficient sampling protocols. In particular the possibility to store VOCs could be a valid approach. In parallel a second component for the platform has been tested. It is represented by the VOCs analysis technique which uses a Tenax tube as a storing system for the gaseous head space. One of the main advantages is represented by the possibility of non contaminant gas transportation. In fact the storing action can be done even many days before the moment where the measurement by an EN of the conserved gas is done. Another significant advantage of this technique is the fact that the increase of the adsorbing time produces a chemical amplification very useful when certain VOCs are present at very low concentration (ppb or lower). Athirdfeatureofthisapproachconcernstheuseofatemperature differentiated desorption(TDD) which can allow the VOCs output at different temperature intervals which are responsible of the selection of desorbed VOCs. TDD is proved to be very useful for a better analysis with the EN due to the fact that in this way sensors constituting the EN are not charged simultaneously by all the adsorbed chemicals. Figure 2: Typical response fingerprint registered for the liquid (left) and gas (right) composition of a urine sample as output of the sensor system. The third component of the platform is the electronic tongue (ET) which can perform chemical imaging of water or other liquids when they are contaminated by additives which can be liquid or gaseous or even soluble particles. In our case the urine head space sample is fed into the reference liquid where it releases some substances that are representative of the kind of urine under test. In the first experiments a voltammetric sensor has been used. The system composed of a dedicated electronic interface to detect small signals with an optimized S/N ratio is the last version developed at University Campus Bio-Medico di Roma [9]. The peculiarity of this sensor system is the possibility to build a chemical image directly from liquids. Providing different potentials to the electrodes
  • 3. 3/3How to cite this article: A D’Amico, M Santonico, G Pennazza, Y Cavalieri, G Farullo. A Sensor Multiplatform for Non Invasive Diagnosis of Prostate Cancer. Significances Bioeng Biosci. 1(2). SBB.000509.2018. DOI: 10.31031/SBB.2018.01.000509 Significances Bioeng Biosci Copyright © A D’Amico Volume 1 - Issue - 2 immersed in the solution allows to detect small changes of current due to the chemical features of the sample. Each current response permits to built a specific fingerprint of the samples as the one provided by the EN for the headspace. In the Figure 2 a typical urine fingerprint is shown. The fourth component concerns the direct use of the (ET) to perform chemical imaging of the liquid sample; in this case it is possible to detect other useful features able to contribute to the performance increase of the global platform characteristics. It is worth pointing out that the urine is only one of the possible biologic liquid that can be advantageously analysed by the diagnostic platform. The different techniques described above, can be applied individually or jointly. In each case the number of sensors could be very high. The obtained fingerprints are based on non-selective sensors. This is valid both for headspace sensors and liquid sensors. All sensor responses can be analysed using multivariate approaches distinguishing in unsupervised and supervised technique. In the first case it is possible to obtain information about the macroscopic behaviours of data and their correlation with the pathologies considered in the study. These analyses are performed taking into account the standard deviation distribution of the data, elaborating for example a Principal Component Analysis (PCA) model. A different approach can be used when the sensors or the sensor systems are calibrated to specific substances. In this case a model based on a supervised approach (e.g. Partial least square– Discriminant Analysis) can be utilized and validated to predict the concentration of a specific compound both in liquid and gas phase. Conclusions Purpose of this brief note on the prostate cancer detection, which does represent but only one of the possible examples that strongly impact our society, is to underline the importance of the pluridisciplinary approach which is more than necessary when an effective diagnostic method has to be tested for its practical utilization in a screening context. Medical people and engineers more and more should learn how to melt their respective cultures in common objectives especially those concerning the people health. Here we have considered a platform of techniques whose destiny is certainly that to play a significant role in those particular moments that deal with a prompt and non invasive diagnosis. It is worth pointing out that the platform here introduced can be easily utilized by medical people due to the friendly approach considered in the design phase of the measurement systems. References 1. American Cancer Society. Cancer facts & figures 2016. 2. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, et al. (2014) EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65(1): 124-137. 3. Loeb S (2014) Guideline of guidelines: prostate cancer screening. BJUI 114(3): 323-325. 4. Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, et al. (2014) Overdiagnosis and overtreatment of prostate cancer. Eur Urol 65(6): 1046-1055. 5. Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, et al. (1994) Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 151(5): 1283-1290. 6. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al. (2004) Prevalence of prostate cancer among men with a prostate- specific antigen level < or =4.0 ng per milliliter. N Engl J Med 350(22): 2239-2246. 7. Asimakopoulos AD, Del Fabbro D, Miano R, Santonico M, Capuano R, et al. (2014) Prostate cancer diagnosis through electronic nose in the urine headspace setting: a pilot study. Prostate cancer and prostatic diseases 17(2): 206-211. 8. Bernabei M, Pennazzaa G, Santonicoa M, Corsi C, Roscioni C, et al. (2008) A preliminary study on the possibility to diagnose urinary tract cancers by an electronic nose. Sensors and Actuators B: Chemical 131(1): 1-4. 9. Santonico M, Pennazza G, Grasso S, D’Amico A, Bizzarri M (2013) Design and test of a biosensor-based multisensorial system: A proof of concept study. Sensors 13(12): 16625-16640. Your subsequent submission with Crimson Publishers will attain the below benefits • High-level peer review and editorial services • Freely accessible online immediately upon publication • Authors retain the copyright to their work • Licensing it under a Creative Commons license • Visibility through different online platforms • Global attainment for your research • Article availability in different formats (Pdf, E-pub, Full Text) • Endless customer service • Reasonable Membership services • Reprints availability upon request • One step article tracking system For possible submissions Click Here Submit Article Creative Commons Attribution 4.0 International License