a world of extreme miniaturization...total revenue 2014: 360m€ 445 m€ in 2016 > 1 billion €...
TRANSCRIPT
The potential of nanolectronics in healthcare
MCH 50 jaar viering– 1 oktober 2016
Johan Van Helleputte, Senior Vice-President Strategic Development O.R.
A world of extreme miniaturization
2
SCOPE OF THE TALK
ICT
(health care processes)
NANOTECHNOLOGY
SEMICONDUTORS BIG DATA
Seen from an imec viewpoint as privileged player in nanoelectronics
Outline
1. Some high level challenges in health care
2. Why are semiconductors heavily involved in healthcare 3. A vision on the revolution of healthcare and some concrete examples and impact for first-line medicine
Some major health care challenges
4
Global healthcare spending
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
196019701980199020002009
Totalspendingonhealthcareasa
percentageofGDP
USA
Europe
Japan
Data from EFPIA (http://www.efpia.eu/pharmaceutical-industry-
figures-edition-2012)
17.4%
8.5% 9.6%
$2.6T
$6.5T
$1.9T
$1.2T
=
=
=
US Health Spending Drivers
$2.6T
0 500
Cardiovascular
Diabetes
Lung disease
Alzheimer's
(in $B)
$430B
$150-170B
US
31%
Hospital
care
20%
Physician/
clinical
20%
Other
care Nursing home care
Home health care
Professional services
10%
Drugs
19%
Other
Chronic disease 75% of $2.6T
7/10 deaths
Data from Martin A.B., et al., Health Affairs, 2012.
US Health Spending Drivers
$2.6T
0 500
Cardiovascular
Diabetes
Lung disease
Alzheimer's
(in $B)
$430B
$150-170B
US 2010
31%
Hospital
care
20%
Physician/
clinical
20%
Other
care Nursing home care
Home health care
Professional services
10%
Drugs
19%
Other
Chronic disease 75% of $2.6T
7/10 deaths
Data from Martin A.B., et al., Health Affairs, 2012.
1. Shift: hospital other settings. 2. Efficacy, efficiency to increase AND cost of technology to drop: extreme miniaturization for expensive equipment 3. Optimization of health care processes (ICT-driven) for cost saving
60%
60%
51%
50%
48%
47%
40%
30%
Asthma
Cardiac Arrythmias
Migrane
Rheumatoid arthritis
Osteoporosis
Hepatitis C virus
Incontinence
Alzheimer's
Oncology
Spears et al. TRENDS in Molecular
Medicine Vol. 7 No. 5 May 2001
Therapeutic Area Effective Rate (%)
Pharma Challenge: pressure on block buster model (2001)
25%
EFFICACY OF DRUGS – 10 years later
Sourc
e: “
Pers
onaliz
ed M
edic
ine”
, Jam
es W
eis
and
Lily
Ch
an, A
pri
l 20
10
Need for personalized (precision) medicine (initially driven by Herceptin case).
Decision making in Healthcare requires collecting and analyzing increasingly complex data
Challenge of Big Data
- Unraveling of (multi-factor) disease mechanisms
- Genetic mapping through DNA Sequencing
- Co-morbidity interactions
- Multi-omic approaches - Disease monitoring & management (“zorgplan”)
- Precision/personalized disease models (in a further future)
- …
11
NEW MEDICAL ENTITIES (NME) – some key facts
1) 12 – 14 years from idea to market introduction
2) At a cost of 2 to 5 B$/NME
3) With an attrition rate of >65% at the end of Phase III clinical phase
12
WHY IS THIS?
- Limited data points (budgetary reasons/technology)
- Lack of early abortion
- Transition from animal to human model often problematic
- Quality clinical trials (a lot of drop-outs)
- Logistic nightmare clinical trials (esp. phase III)
- More severe attitude payors & regulators
We are seeing severe changes in health landscape
13
Trends
Low hanging fruit over, patent cliff, blockbuster model under pressure, higher pressure payors & regulators, …
Broken Pipelines Pharma
1
Efficacy of therapies increasingly requested (cDx) on individual cases, … Power shift to
Payors All
2
cDX, disease management, personalized (precision) medicine, preventive medicine, …
Moving Beyond traditional Diagnosis
Pharma/Dx
3
Source: Johns Hopkins Medicine
14
Trends
Better & cheaper tools becoming available for Dx (diagnostics) & Rx (therapy), potential of ICT & semiconductors, better insights in disease mechanisms, …
Shift in Technology
Focus Dx
4
Shift Shift from point-of-care (POC) to point-of-need (PON)
Increasing Push For Near Patient Testing
Patients
5
Reimbursement strategies reconsidered (outcome based)
Reimburse-ment Strategies
Evolving All
6
Source: Johns Hopkins Medicine
We are seeing severe changes in health landscape
Diagnostics trend from central labs to Point-of-Need
PON
Source: Adapted from Roche investor deck
15
16
Right biomarkers Disease
mechanisms
Diagnostics & cDx
Therapy
Precision disease management
- Therapy compliance - Dose optimization (toxicity) - Therapy resistance
Health care cycle
Big Data
17
Right biomarkers Disease
mechanisms Diagnostics
& cDx Therapy
Precision disease management
- Therapy compliance - Dose optimization (toxicity) - Therapy resistance
Health care cycle
Big Data
Role of NanoElectronics in LS (at imec)
= role for nanoelectronics
Semiconductors for Life sciences
Why imec in healthcare?
▸ Total revenue 2014: 360M€ 445 M€ IN 2016
▸ > 1 Billion € infrastructure installed
▸ >1.4 Billion € new investments planned & being
deployed)
▸ Partnerships with > 600 companies & 208
universities on a global scale
▸ 37 spin-off companies
▸ Headcount 2015: 2300 (excl. iMinds = +1000)
- 1613 imec staff
- 385 industrial residents
- 300 PhD students
- 73 nationalities
FACTS & FIGURES
89% contract
R&D
11% subsidy
RESEARCH PROGRAMS
ELECTRONICS FOR HEALTHCARE & LIFE STYLE
W IRELESSCOMMUNICATION
IMAGE SENSORS & VISION SYSTEMS
ENERGY SENSOR SYSTEMS
FLEX IBLE ELECTRONICS
CORE CMOS
LITHOGRAPHY DEVICES INTERCONNECTS
AP
PL
ICA
TIO
N
DR
IVEN
RESE
AR
CH
TE
CH
NO
LO
GY
D
RIV
EN
RESE
AR
CH
HETEROGENEOUS INTEGRATION
MEMS SENSOR PHOTONICS
Imec has grown over the past 30 years into the largest independent research center for nano-electronics
It uses its unique expertise, infrastructure and technology tool box (horizontal layer) to build game changing
application oriented platforms (verticals) deeply rooted in the horizontal backbone.
21
22
Goals & ambitions in health care
Supercomputers run by consumers
1950 $6,000,000
cm-sized switches
5,000 operations/sec
27 tons
2015 $500
14 nm switches
>30,000,000,000 operations/sec
140 grams
x109
History repeats itself in Life Sciences
x109
Dx
Healthcare @ imec
Body Area Networks
External measurements: ECG,
EEG, galvanic skin response, pulse
oximetry, blood pressure, sweat,
accelerometers, etc.
Life Science Technologies
Measurements of molecules and cells:
molecular diagnostics (DNA, proteins,
metabolites), cytometry, point-of-care
diagnostics, bioreactors, DNA sequencing
Applications: Cancer, infectious diseases,
regenerative therapy, neurodegenerative
diseases, pre-natal diagnosis, consumer health
(biomarker-based), companion Dx
Applications: Neurodegenerative diseases,
consumer health (stress, fitness), cardiovascular
health monitoring
JHU/imec confidential information - December 2014 25
Health patch ECG PATCH
▸ Ultra-low power ECG patch
▸ Bluetooth ultra low energy
▸ Embedded algorithms
▸ 30 days autonomy
RISE IN VALUE CHAIN IS PAYING OFF:
5-YEAR PARTNERSHIP WITH CARDIONET/now
Biotelemetry First FDA approval @ imec/BT
27
WIRELESS EEG
Applications:
▸ Improving traffic safety through drowsiness monitoring
▸ E-learning that adapts to the user’s concentration
▸ Accurate EEG monitoring at home, e.g. epilepsy patients
FROM PLATFORM TO PRODUCT FOR CLINICAL RESEARCH - “with imec R&D innovations inside”
http://www2.imec.be/be_en/press/imec-news/neuropro.html
Miniature spectrometer-on-a-chip with the performance of a bench-top instrument at a fraction of the size and cost
Wearable high-performance spectrometer
conventional bench-top instrument with comparable sensitivity
SiNx photonics
30
TOWARDS < 100€ ‘Genome Chip’
31
From: https://www.genome.gov/27541954/dna-sequencing-costs/
OK for clinical targeted seq applications
Pacific Biosciences single molecule real time sequencing instrument
imec confidential information –2015
Goal: democratizing of DNA sequencing and a crucial pillar for precision medicine
Core $500k machine…
on single, disposable chip
NEXT-next-GEN DNA Sequencing instrumentation-on-a-chip
Single molecule
real time DNA
sequencing
imec confidential information - 2015
7x faster 3x smaller 2x cheaper
Grand challenge: biocompatible miniature electronics
that directly interfaces with the body’s control system:
neurons
34
NEUROSCIENCE LAB-ON-A-CHIP
35
100 µm x 50 µm shank
456 electrodes and amplifiers
52 channels
Low noise: 4µV rms
Recording + stimulation
Replacing >100 kg of tools
for a current neuro-science
experiment!
Signal filtering (LFPs , APs)
Analog-to-digital conversion
Digital interface to small PCB
Direct link to PC
Next generation request >1400 electrodes on a shaft
of < 20 micron diameter, sponsored by leading foundations
36
K.U.LeuvenUniversity Hospital
VIBBiotechnology
imecNanoelectronics
NeuroElectronics Research Flanders
Combining very complementary expertise and critical mass in a unique way at a single
site for exploring the dynamics of neuronal connections in our brain.
37
circulating tumor cell
38
CYTOMETRIE: measuring characteristics of cells
circulating tumor cell
CTC diagnostic
market will be $7.9B
by 2018 Transparency Market Research
“Circulating Tumor Cells (CTCs) and
Cancer Stem Cells (CSCs) Market –
Global Scenario, Trends, Size, Growth and
Industry Analysis, 2011 – 2018.”
CTC-based diagnostics will require improved cell detection and isolation solutions that combine high throughput, high sensitivity, multi-modal detection (fluorescence + imaging), and the ability to isolate cells of interest for downstream analysis by next-gen sequencing. We are working on a platform cell manipulation technology that supports the required specifications.
CURRENT CYTOMETRY APPROACHES
• Amnis ImageStream • Flow cytometry with microscopic
imaging
• Conventional microscope
• 1000 cells/s
• Research tool, not for clinical use
FACS (Fluorescence-activated cell sorting)
▸ Beckman-Coulter, Sony (iCyt), Applied Biosystems, BD Biosciences
▸ Research tool (complex to operate)
▸ Biomarker based
data rich
fast
on-chip
cell-sorter
imaging
cytometer
FACS
blue ocean
red sea
40
High-throughput imaging flow cytometer
Input
Output stream 1
Output stream 2
Fast microfluidic bubble-jet
cell routing
Aim is to scale to 20,000,000 cells/s
(identification & sorting)
>1000-fold improvement over current system
Allowing for new applications such as detecting
single circulating tumor cells in a blood
sample.
On-chip high-resolution imaging for
cell classification
In-flow cell tomography
MCF-7
cell
In-flow phase contrast
imaging
41
MiLab Moving the needle in Diagnostics
42
Blood cells
Proteins
Lipids
RNA/DNA viruses
BLOOD CONTAINS A TREASURE OF INFORMATION
... and much more
Diagnostic Testing is largely confined to the centralized laboratory
IN VITRO DIAGNOSTICS USING BLOOD SAMPLES
Takes a few minutes
Decentralized (portable)
at point-of-need
Preferably directed towards prevention,
next to supporting therapeutic decisions
& disease management
Takes one to a few hours (hospital) to
a few days (physician)
Centralized
Curative
CURRENT DIAGNOSTICS FUTURE DIAGNOSTICS
INTEGRATE MULTIPLE STEPS ON A SINGLE CHIP
Example : Hepatitis C virus
NUCLEIC ACID AMPLIFICATION (PCR)
LYSIS + NUCLEIC ACID EXTRACTION
PLASMA SEPARATION
BLOOD
Sample prep on chip !
MiLab: Low cost, accurate, cloud-connected, multi-omic
diagnostics that works via open standard on a device you
already own
CRP
Troponin
CK-MB
Triglycerides
HDL
LDL
Neutrophil/Lympho
cyte ratio
Multi-omic
47
The Partners: JHM & IMEC
PARTNERSHIPJOHNS HOPKINS UNIV
PRESS RELEASE
Imec and Johns Hopkins University team to expand healthcare applications
for silicon nanotech
Leuven (Belgium) October 24, 2013 - Researchers and physicians at Johns Hopkins University will
collaborate with the nanoelectronics R&D center imec to advance silicon applications in healthcare,
beginning with development of a device to enable a broad range of clinical tests. The corresponding
tests will be performed outside the laboratory. The collaboration, announced today, will combine the
Johns Hopkins clinical and research expertise with imec’s nanoelectronics capabilities. The two
organizations plan to forge strategic ties with additional collaborators in the healthcare and technology
sectors.
“Johns Hopkins has always prioritized innovative and transformative research opportunities,” said
Landon King, MD, the David Marine Professor of Medicine and executive vice dean of the school of
medicine. “Our new collaboration with imec is such an opportunity, and we very much look forward to
leveraging our respective strengths across the university in biomedical and nanotechnology research to
improve patient diagnosis and care throughout the world.”
Imec and Johns Hopkins University hope to develop the next generation of “lab on a chip” concepts
based on imec technology. The idea is that such a disposable chip could be loaded with a sample of
blood, saliva or urine and then quickly analyzed using a smartphone, tablet or computer, making
diagnostic testing faster and easier for applications such as disease monitoring and management, disease
surveillance, rural health care and clinical trials. Compared with the current system of sending samples
to a laboratory for testing, such an advance would be “the healthcare equivalent of transforming a rotary
telephone into the iPhone,” said Drew Pardoll, MD, PhD, the Martin Abeloff Professor of Oncology.
Pardoll leads the advisory board for the Johns Hopkins-imec collaboration, which will work to extend
new applications of silicon nanotechnology into multiple areas of medicine.
“This relationship with Johns Hopkins is an important step toward creating a powerful cross-disciplinary
ecosystem with consumer electronics and mobile companies, medical device manufacturers, research
centers and the broader bio-pharma and semiconductor industries, to create the combined expertise
required to address huge healthcare challenges that lie ahead,” stated Luc Van den Hove, CEO at imec.
“Only through close collaboration will we be able to develop technology solutions for more accurate,
reliable and low-cost diagnostics that pave the way to better, predictive and preventive home-based
personal health care.”
Rudi Cartuyvels, senior vice president of smart systems at imec, added, “The unique combination of
imec’s nanoelectronics expertise with Johns Hopkins’ proven medical sciences and clinical expertise will
disposable micro-fabricated
test
flexible: blood, saliva, urine
smart phone
health tracking
app + web services
Wireless link
<10 grams <1 cm3
~$10 < 15’ TTR
THE PARTNERS IMEC-JHU: A UNIQUE AND GLOBAL ALLIANCE
miLab / miDiagnostics INITIATIVE
60M€ series A (May 2015)
Accurate diagnostics anywhere, anytime for anyone
Low-cost, Si-based disposable
Leveraging standard semiconductor manufacturing:
scalable to low-cost mass production
Small form factor
Use ubiquitous device as interface (e.g. smartphone)
No separate instrument
Quantitative, accurate and clinically relevant
Sensitivity and specificity that matches reference
methods
Multi-omic
Integration of various assay and sensor types on one
platform
Currently 4 different “pathways” planned
Detection chip
~1 cm
2-4 cm
Fluidics chip
PCB with
radio, power,
control
Packagedisposable
microfabricated test
flexible:
blood, saliva, urine
smart phone
health tracking
app + web
services
Wireless link
<10 grams
<1 cm3
~$10
<15 min
Concept
MiLab : Dx for very different disease areas
Disease screening & Disease management &
follow-up
1
Point of Urgent & Critical Care
3
GP aid for distinguishing fever causes in patients
2
Key Analytes
Nucleic Acid Pathway
Antibody/Protein Pathway
Metabolite Pathway
Cell/Cytology Pathway
Key Applications
Consumer application
4
50
Time to result (TTR) in < 15’
Sou
rce:
Jo
hn
s H
op
kin
s M
edic
ine
Unmet medical needs
INFECTIOUS DISEASES in resource limited regions
• Urgent need for Point-of-Need (PON) MDx tests which match the WHO
ASSURED criteria (special focus on HIV, TB & Malaria):
- Affordable (around 2$)
- Sensitive
- Specific
- User-friendly
- Rapid (<15’) & Robust
- Equipment/instrument free
- Deliverable at place of need (not hospital or lab setting)
• Current POC Dx tests, mostly based upon lateral flow technology:
- Lack of sensitivity
- Lack of specificity
- Not instrument-free
- Often not quantitative
- No direct link to health care ITC network 51
PoN Viral load tester: very high need in developing countries
• Strong need for PON viral load tester: this is an unmet need in most of the developing
countries: - Need is very urgent and large (measuring pathogen/viral DNA or RNA concentrations is
crucial for efficient disease management (compliance, dose optimization, therapy resistance)
and for avoiding re-infection
- Only limited number of expensive viral load testers available in those countries and only in lab
environments (need for special infrastructure & medical expertise)
- In rural areas no access viral load testers. By lack of viral load testers, CD4+ count is done,
which is a poor measurement for disease management.
• Many ID are spreading again or need to be contained: - TB
- Dengue fever
- West-Nile Virus
- HIV
- Malaria
- Sleeping sickness
- HCV
Need for easy to use and cheap PON viral load tester: none existing today: iLab is a perfect candidate.
Imec’s view on the FUTURE of MICROSCOPY
Microscope on chip
CMOS processing
SiN Photonics
Bio-sample
Hologram
Image reconstruction
Integrated light source
Traditional microscope
Diffraction pattern
On-Chip microscopy
Traditional phase-
contrast microscope
Lens-free imager @ imec
Intensity Phase
Human induced pluripotent stem cells
170 µm
54
Miniaturization of blood analysis devices
3-part white blood cell differential
Vercruysse et al., Lab on a chip, 2015
Granulocytes
Monocytes Lymphocytes Inte
rnal co
mp
lexity
Cell size (µm)
Ultra-fast PCR: 40 cycles in < 3 minutes
Scroll further
to 35 seconds
Temperature [°C] Time [s]
98.0 32s
96.0 2s
62.0 2s 40 cycles
Standard 30 cycles PCR > 45+ min.
57
NEXT STEPS
Creation platform & IP company: done (60 M€ SERIES A) Integration building blocks: on-going Clinical validation: starting early 2017 at Johns Hopkins Medicine Regulatory approval: planned 2018 Commercialization: planned for early 2019
58
BIG DATA
EXASCIENCE L IFE LAB
HIGH PERFORMANCE COMPUTING IN LIFE SCIENCES FOR BIG DATA
First focus
• 1. Analytics of DNA sequencing
• 2. In-silico modeling for drug development
Thank you so much!
Discussiepunten (cijfers 2012, ITINERA rapport 2014):
- 70 – 80% zorguitgaven voor chronische aandoeningen (staan ook in voor 70-80% mortaliteit) - 27% Belgen heeft chronische aandoening - Preventie in België is bedroevend laag (0.9%) in vergelijking OESO (2.9%) - Administratie is duurder: 5.2% tov 3.1% OESO gemiddelde - Curatieve zorg en revalidatie: 52.2% budget gezondheidszorg - Gezondheidzorg staat wel in voor 12% beroepsbevolking - Iedere 1% gewonnen kwalitatieve levensjaren op totale actieve bevolking = + 6% BBP (creatieve toegevoegde waarde, koopkracht,…) - België zeer hoge werkbelasting met 11 patiënten/verpleegkundige kwalititeitsrisico’s - 2/3 kwaliteitsproblemen gevolg van ondermaats functioneren in teamverband en van gebrekkige communicatie - Nood aan zorgcontinuum (nu sterk acuut probleemoplossend)
Discussiepunten (cijfers 2012, ITINERA rapport 2014):
- Nood aan complementaire, doelgerichte aanpak via integraal zorgplan - Impliceert ander betalingssysteem en verdienmodel (gezondheidswinst gedreven, geen zero sum game): combinatie van prestatiegericht en meerwaardengedreven - Nood aan meer horizontale organisatie ipv verticale specialisatie organisatiestructuur - Absolute nood aan geïntegreerde ICT systemen (intra & extra muros) als basis integrale zorg - Te veel regelgeving op micro-niveau en te hoge administratieve druk - Rol van overheid eerder kwaliteitsbewaking via kwaliteitsboordtabellen op basis van gezondheidswinst & TQM - Volgens Kaiser Permanente: ruimte voor 25% besparing zorgkosten zonder kwaliteitsverlies door: uniformisering, digitalisering en centralisering van gegevens - Quid koppelen van remgeld aan combinatie van:
• Verantwoordelijk gedrag van patiënt (keerzijde van empowerment) • Kwaliteit van de gekozen zorginstelling (concurrentiebevorderend)
Take away messages GPs