This document describes an integrated platform to enable point-of-care theranostic applications in primary care. The platform consists of three components: TheraTEST for sample analysis, TheraPOC for device operation, and TheraGUIDE for treatment guidance. TheraTEST uses a cartridge-based system to simultaneously test samples for multiple pathogens and antibiotic resistance in under 30 minutes. The platform aims to improve clinical outcomes, reduce costs, and combat antibiotic resistance through rapid diagnostics and treatment guidance at the point of care. The project involves 16 partners across 9 countries to develop and validate the integrated platform over 4 years with an 11 million euro budget.

1. An Integrated Platform Enabling Theranostic Applications at the
Point of Primary Care
• Industry-driven project to accelerate the adoption “Antimicrobial resistance – also known as drug
resistance – occurs when microorganisms
of theranostic applications in Primary Care. such as bacteria, viruses, fungi and parasites
change in ways that render the medications used
to cure the infections they cause ineffective …
• Built around the high-incidence clinical case of This is a major concern because a resistant
infection may kill, can spread to others, and
early-diagnosing lower respiratory tract infections. imposes huge costs
to individuals and society ...
Lack of government commitment to address these
• Simultaneous test for different pathogens and issues, poor surveillance and a diminishing arsenal
of tools to diagnose, treat and prevent also hinder
their antibiotic resistance aiming to enhanced the control of drug resistance.”
clinical outcomes, improved patient healthcare World Health Day 2011 key health issue, World
Health Organization (WHO)
and reduced costs.
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2. Objective
 Improve treatment efficiency and reduce current pathogens antibiotic
resistance growth by eliminating diagnostic uncertainties and pointing out
the correct specific treatment.
 Achieve a faster clinical turnaround by enabling clinical decision-making
in less than 30 minutes from sample extraction to result delivery.
 Improve analytical performance by employing novel detection techniques
with higher specificity and sensitivity than currently being used alternative
POC analytical methods.
 Stress usability and robustness by promoting the development of
standard analytical and operational platforms.
 Provide economic systems by promoting therapeutic education and
compliance to generate more efficient healthcare economics.
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3. Medical System Overview
TheraTEST - Analytical Platform
Multiple Nucleic Acid Detection without Amplification (PCR)
Disposable Cartridge based in Lab-on-Chip Technology
TheraPOC - Operational Platform
Universal Control Module (POC & Information Instruments)
Plug & Play Semantic interoperability
TheraGUIDE - Therapeutic platform
Applications set build on a Convergent ITC Platform
General Practitioners Support
Fight antibiotic Misuse and Abuse
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4. TheraTEST: Overview
 Built around the high- Result
incidence clinical case of Therapy
early-diagnosing in CA-LRTI.
STEP 1 STEP 4
 In-line to meet the usability 30 Minutes
requirements defined by the
CLIA-waived standards of the
FDA, also applicable for the
European IVD markets.
STEP 2 STEP 3
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5. TheraTEST: Analytical Protocol
 Simplification of the assay into
Suspension Buffer
Lysis (Enz + Cntrls) few steps.
NA purification
Lysis
Buffer Lab-on-a-Chip (LOC) technology
based cartridge.
Liquid Management
Shear (pumping and valves)
Fragmentation  No NA amplification needed.
Probes
Wash buffer Multiplexed assay (8 pathogens
Mag. beads +
Temperature Control panel) with Time to Result under
Hybridization Hyb. buffer
Magnetic Field
30 minutes.
(Enhance
 LASER-based optical detection
hybridization and
purification)
Detection interpreted by automatic
Waste Detection setup algorithms.
Cartridge Envelope Instrument Interfaces
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6. TheraTEST
Automated Integrated Analytical System
P=P -P As
Sample Preparation & NA Extraction → ( the flow).speedthe DNA approaches the
difference
constriction, NA Fragmentation
increases and the coiled
1 2
→ NA Detection & Pathogen
Identification
Streptococcus pneumoniae studies
DNA molecules are elongated and then fragmented by
drag forces when the DNA is located in the constric-
1,8
tions. The series of constrictions are used to reduce the
Fluorescent
1,6 inlet outlet Detection Probe
1,4
Magnetic
Bead
NA concnetration (µg/ml)
microchannel
1,2
1,0
0,8
DNA
motion Figure 3: SEM image of a fragmentation constriction region.
0,6
0,4
Figure 4a shows optical microscopy images of com-
pleted glass microfluidic chips used for DNA fragmen-
0,2 constrictions tation. The lower image shows an example a single
fragmentation channel with multiple constrictions and
0,0
Lysis only on LOC With swab Without swab Figure 1: Schematic drawing of DNA fragmentation device multiple channels with constrictions. Figure 4b shows
using hydrodynamic shearing forces. P= P1-P2. an example of various fragmentation chip designs.
variance in the fragment length distribution. Figure 2 (a)
Micrococcus luteus studies shows a top-view of a single constriction with length L
1,0
and width d, and main channel width a. The angled
0,9
constriction design reduces bubble entry into the frag-
0,8 mentation stream [11].
NA concnetration (µg/ml)
0,7
series
0,6
0,5
parallel
0,4
0,3
0,2
0,1
After collecting samples from different European hospitals, TheraEDGE is
(b)
0,0
currently in pre-clinical validation phase. The different sample-preparation
Lysis only on LOC With swab Without swab
and detection operations have been demonstrated independently.
LOC Tube
Figure 2: Top-view schematic drawing of fragmentation
constriction with length L and width d.
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and fabricated: series constrictions and parallel chan-
nels. The fragmentation devices are fabricated entirely
from glass (Borofloat) substrates. A single lithography
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tion structures and etched in the glass substrate using

7. TheraPOC & TheraGUIDE
Patient GP
TheraPOC Client Protocol
Alarms
Reminders & TheraPOC
feedback Administration
Clinical Interface
(TCP/IP)
Treatment Guidelines
Follow-up TheraPOC
Standard Instrument Interoperability Protocols
POCT1-A2 DML (LPOCT)
TheraGUIDE
Standard Interoperability Protocols
HL7(PDQ)
IHE XDS POCT1-A2 ORI (LPOCT)
eMR HIS

8. Conclusions
 Turnaround times of 30 minutes seem feasible with the current
simplified analytical protocol and system.
 Both the instrument and cartridge prototypes are in-line to meet the
usability requirements defined by the CLIA-waived standards of the FDA,
which would also be applicable for the European IVD markets.
 The overall system and its disposables designed and fabricated at an
affordable by public healthcare systems cost.
 Currently in pre-clinical verification phase; sensitivity being enhanced
(currently 10pM → 1pM aimed).
 The different sample-preparation and detection operations have been
demonstrated independently.
 It has the potential of enhancing antibiotic resistance policies and
promoting tailored medicine.
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9. The Team
• 4 Year Project
• Budget: 11 M€
• Consortium: 16 partners
• 9 Different Countries