Structure of subproject proposal (total length 4-10 pages,
clarifying figures are welcome)
1.1 Subproject full title: Reduction of hospital mortality by micro/nanotechnologybased diagnostic tools
1.2 Subproject Acronym: Nano-ROM
1.3 RISKMAN Research Area: RA2 - System Performance Monitoring and
Diagnostics
2.1 Proposing organisation: ARC Seibersdof research GmBH
2.2 Contact person name: Dr. Gerhard Malainer
2.3 Address: A-2444 Seibersdorf, Austria
2.4 Tel: ++43-50550-3701
2.5 Fax: ++43-50550-3444
2.6 Email: gerhard.malainer@arcs.ac.at
2.7 Web site: http://www.arcs.ac.at/UL/ULB
2.8 Participating organisations and companies, name and country:
ARC Seibersdorf research GmbH (Austria)
Cantion (Denmark)
Sepsis Forum (Members from Belgium, France, Israel)
Robert Koch Institute (Germany)
National Center for Surveillance of Nosocomial Infections (Germany)
3. Proposal summary (1/3 page)
Nosocomial (= hospital-acquired) infections are substantially responsible for the
continuously increasing incidence of mortality in hospitals. In counteracting this
development, early preventive diagnosis is critical. Here, new rapid, nano- and
microbased diagnostic systems show great potential. The aim of the proposed
multidisciplinary consortium is to generate new micro/nanotechnology-assisted
diagnostic strategies to reduce the incidence of nosocomial infection-related
mortality. The project will focus on Sepsis, a severe clinical condition caused by
infection, which particularly manifests in elderly, immunocompromised, and critically
ill patients. Sepsis annually affects estimated 700.000 individuals in Europe and
several millions worldwide with mortality rates of 28-50%. This project aims at
establishing novel DNA microarray - and cantilever technology assays for fast,
nucleic-acid-based diagnosis of microbes causing sepsis (in particular especially
virulent and resistant ones) and their antibiotic resistances. The final goal is to
implement these newly developed diagnostic tools in the daily clinical practise after
thorough evaluation.
4. Objectives (1/3 page)
The major objective of the project is to develop improved strategies for diagnosis,
prognosis and personalised therapy for combating nosocomial infections affecting
typically patients who are immuncompromised because of age, underlying diseases,
or medical or surgical treatment. To achieve this goal conventional methods in
infectious disease diagnosis, which all require microbial growth and therefore last at
least 24 hours, shall be extended by new, nucleic-acid based DNA microarray- and
cantilever assays allowing a diagnosis within a few hours. A fast and reliable
diagnosis is particularly critical in infections affecting patients already under bad
health conditions and in such cases can decide over life or death. Sepsis, as one of
these clinical scenarios, will be the focus of this study. Oligonucleotide probes will be
designed and evaluated, first for identification of the most relevant bacterial species
involved in sepsis, and second for detection of antibiotic resistances these pathogens
typically display. These two sets of detection probes will be both applied to two
different technical platforms, namely DNA microarrays and cantilever technology. The
platforms will be compared in their performance and finally tried to be implemented in
the daily clinical practise.
5. Deliverables (new products, new processes and services, radical innovations;
prime deliverable is expected to be a breakthrough in applicable knowledge to be
transferred to industry and society):
A novel fast, reliable, nucleic acid based assay for -in particular highly virulent and
resistant- bacterial species and antibiotic resistance detection in sepsis taking
advantage of nanotechnology tools such as DNA microarrays and cantilevers.
In more detail:
 Specifity-confirmed oligonucleotide probes which allow the identification and
differentiation of all sepsis-relevant infectious bacterial species.
 Oligonucleotide probes for detection of antibiotic resistance genes found typically
in the focused sepsis-relevant bacteria.
 Oligonucleotide microarray for pathogen identification (BactID-chip)
 Cantilever-based assay for pathogen identification (BactID-Cant) using the same
probe set as for the BactID microarray
 Oligonucleotide microarray assay for antibiotic resistance detection (ABR-chip)
 Cantilever-based assay for antibiotic resistance detection (ABR-Cant) using the
ABR-chip probe set
6. Justification and potential impact (economic impact, direct and indirect economic
benefits, European dimension, training and education, conformity with EC societal
objectives: quality of life, health, safety, working conditions, employment, and
environment)
With the great and prolonged morbidity associated with sepsis and the intensive care
required, the healthcare expenditures for treating patients with sepsis in Europe and
elsewhere in the world are profound. Despite enormous investment in intensive care,
sepsis is still associated with mortality rates ranging from 28% to 50%. Due to the
lack of fast diagnostic assays medical doctors face the problem to be forced to use
broad spetrum antibiotics instead of specifically microbe-targeted drugs which leads
to a further increase of antibiotic resistant bacterial strains. As a consequence, the
development of new drugs becomes more and more difficult and expensive
increasing health expenditures further.
The novel diagnostic tools developed in this project should not only reduce mortality
rates associated with nosocomial infections but also inhibit a further increase in
antibiotic resistance since they allow a more specific antibiotic therapy.
.
7. Description of the work (technological approaches and methods, work tasks, their
description, deliverables and work effort in person months) marked according to the
following components (RTD = Research, technological development and innovationrelated activities, DEM = Demonstration activities, TRA = Training)
WP1: Probe design
Technical approach / methods: Use of appropiate softwares
- ARB suite software for designing specific probes within
the 16 S rRNA genes of sepsis-relevant bacterial
species
- Software developed by iSenseIt for designing probes
and multiplex PCR primers for detection of antibiotic
resistance genes
Work effort in person months : 4 (=RTD)
Partners involved: ARC Seibersdorf research GmbH
WP2: Working protocol for DNA microarray assays
(BactID-chip + ABR-chip)
Technical approach / methods:
- Evaluation and comparison of DNA isolation methods
- Comparison of different target labelling methods
- Probe specifity testing
Work effort in person months : 44 (RTD 42 TRA 2)
Partners involved: ARC Seibersdorf research GmbH
WP3: Working protocol for cantilever assays
(BactID-Cant + ABR-Cant)
Technical approach / methods:
- Tests on probe to substrate coupling , on target to
cantilever tip coupling respectively
- Probe specifity testing
Work effort in person months : 15 (RTD 13 , TRA 2)
Partners involved: Cantion
WP4: Evaluation and clincial implementation of developed assays
Technical approach / methods:
- Tests on specifity and reliabilty of all kinds of
developed assays (BactID-chip, BactID-Cant, ABRchip and ABR-Cant) using reference bacterial strains
and sepsis patient samples (blood , blood cultures)
- Conventional diagnostic tests on pathogen
identification and antibiotic resistance to evaluate data
from the newly developed diagnostic tools
- Training activities
- Implementation of assays in selected diagnostic labs
Work effort in person months : ARCS 20 (16RTD, 4DEM), Cantion 15 (12RTD,
3DEM), Clinics 10 (8RTD, 2 TRA)
Partners involved: ARC Seibersdorf, Cantion, Clinical partners (Sepsis Forum, RKI,
National center for surveillance of nosocomial infections)
8. Partners involved, partner profiles (business idea, size, competence) and the role
of each partner
Partner
Chief scientist
Business idea
Competence
Role in proj
ARC Seibersdorf
Christa Nöhammer
Austrian center for
cDNA and
Probe desig
research GmbH,
Biotechnology unit
applied research
(Seiberdorf, Austria)
Cantion
(Lyngby, Denmark)
Carsten Faltum
(CEO)
Jean L. Vincent,
(International society) (Erasmus Hospital,
Belgium)
Jean Carlet (Hospital
St. Joseph, France)
Charles Sprung
(Hadassah Hebrew
University, Jerusalem)
Robert Koch Institute Prof. Witte
(Head of Staphylo(RKI, )
coccus reference
Wernigerode,
center)
Germany
National Center for Prof. Rüden
Sepsis Forum
Surveillance of
Nosocomial
Infections
SME
Society
RKI = German
reference center for
microbiologyrelated aspects
Surveillance of
Nosocomial
Infections
oligonucleotide
Developmen
microarrays, , probe BactID- and
design, slide surface microarrays
chemistry
Cantion designs,
Developmen
develops and
BactID- and
manufactures
cantilever as
advanced biochips
for label free detection
of molecules (cantilever technology)
Specific interest in Supply with
sepsis, collections of strains and
sepsis-relevant
patient samp
pathogens
Among others they
all
have a Staphylococcus strain
collection
Access to
nosocomial infection
causing microbes
Berlin, Germany
9. Resources for total subproject and for each partner (resources needed: personnel,
equipment etc; costs, work effort in person months)
ARCS:
Cantion:
Clinical Partners:
68 person months = 455.600 Euro (calculated with 50 Euro/hr)
Material 75.000 Euro
30person months = 201.000 Euro
Material 50.000 Euro
10 person months = 67.000 Euro
Material 20.000 Euro
Total subproject : 868.600 Euro (total costs for person months: 723.600 Euro;
total material costs: 145.000 Euro)
10. Duration (starting date, duration in months)
WP1
WP2
WP3
WP4
starting date
month 0
month 1
month 3
month 21
duration in months
4 months
20 months
12 months
16 months
Supply with
strains
Supply with
strains
Total duration of the project: 36 months
11. Financial plan
First year: 247.900 Euro (person months), 45.000 Euro (material)
Second year: 201.000 Euro (person months), 40.000 Euro (material)
Third year: 274.700 Euro (person months), 60.000 Euro (material)
Total: 723.600 euro (person months), 145.000 Euro (material)
12. Other issues (e.g. ethical, gender, EC policy related issues)
The project will be performed in accordance with the ethical principles in widely
recognised international texts or codes of practise. All patient samples, collected for
WP4, will be coded and identifed only by the code.
One of the basic criteria defined by the Eurpoean Commission for Research
activities to be funded in the 6th frame program is the focus on nanotechnology and
health. This project will cover both aspects applying nanotechnology to develop new
tools in infectious disease diagnosis to reduce nosocomial infection-related mortality
in hospitals. The creation of a consortium with complementary expertises (DNA
microarrays, Cantilever technology, clinicians) will enable a multidisciplinary
approach to realize the focused task.