Funded by the European Union - GA 737089 1

ChipScope, a new microscope on a chip

with superresolution capabilities

J. Daniel Pradesdprades@el.ub.edu

University of BarcelonaDepartment of Electronic and Biomedical Engineering

FET-OPEN “Overcoming the Limits of Diffraction with SuperresolutionLighting on a Chip”, 2017-2020.

Workshop: “European Initiatives for the Next Generation of Nanoscopies in Biosciences”

Funded by the European Union - GA 737089 2

Introduction: Optical Microscopy Limits

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Introduction: Optical Microscopy Limits

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Introduction: Superresolution Microscopy

E. Beitzig, S. W. Hell, and W. E. Moerner, “How the optical microscope became a nanoscope,” in The Nobel Prize in Chemistry, The Nobel lectures (Stockholm University, 2014).

Funded by the European Union - GA 737089 5

Introduction: Superresolution Microscopy

Scientific Reports volume 6, Article number: 27290 (2016)

Structured Light

Stimulated Emission

Localization

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Introduction: Superresolution Microscopy

2m

• Time consuming• Sample preparation• Harsh light intensities• Cost of the instrument

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The Idea

▪ An optical microscope on a chip …

▪ … with superresolution capabilities

𝐟𝐞𝐚𝐭𝐮𝐫𝐞 𝐬𝐢𝐳𝐞 <𝛌

𝟐

2m

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The Idea

1m

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Superresolution on a ChipScope

o Sample in contact with Light pixels (LEDS)

o Lensless microscope

o Shadow imaging

o ~ 100W/cm2 up to kW/cm2

(~10kW/cm2 STORM, ~150 MW/cm2 STED)

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The components

<𝛌

𝟐

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The imaging modes

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The imaging modes

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The imaging modes

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G. Scholz et al.

Lensless microscopes

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o Array of individually addresable LEDs with size < λ/2

• 64x64 LEDs of 50nm

• 16x16 LEDs of 1μm

• 32x32 LEDs of 200nm

Imaging modes in ChipScope

Funded by the European Union - GA 737089 16

Metalorganic Chemical Vapor Phase Epitaxy (MOVPE)

GaN growth for blue LEDs:• 60 wafers, 2 inch diameter • 400 LEDs per wafer • 24.000 LEDs per growth run

Key components: individually addressable nanoLED array

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Key components: individually addressable nanoLED array

Micro/nano GaN LED arrays• processing • nanocharacerization

Funded by the European Union - GA 737089 18

Key components: individually addressable nanoLED array

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Key components: nano LED Optical simulations

Multiscale simulation

ITO

ITO

air

air

Ga

NG

aN

sapphire

sapphire

sapphire

air

Water

Ga

N

Funded by the European Union - GA 737089 20

Electricfield

Key components: nano LED Optical simulations

MQW emission

Fluidic microchannel

Simulation of 100nm LED array

Funded by the European Union - GA 737089 21

Geiger Mode:• Bias: (10%-20%) ABOVE VBD

• BINARY device

• Count rate limited

• Gain: “infinite” !!

Key components: SPAD detector

R.Haitz, J.Appl.Phys. 35, 1370 (1964), J.Appl.Phys. 36, 3123 (1965)

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Key components. SPAD detector

Fabricated in 0.35um CMOS

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Key components: Sample holder

waste

Block diagram of biosensor fluidics

1

2

3

4

5

aspire

pump

ChipScope

microfluidics fluidic valves

fluid:

syringe

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Key components: Sample holder

Thermally stabilized holder

Microfluidicchannel

Temperature sensor

Tubing

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Microscope system integration

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Microscope system integration

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~200 um

SPADSU8

3 mm 450-550 um

LEDs array

SU8 200 um

650 um 800um

550 um<100 um 350 um

Gap

2 mm

200 um

3 mm

X - stage

Y - stage

Z -

stag

e

800um

~100 um

SPAD COARSEMARK

Peltier

Heat Sink

Tilt&Rotation - stage

uFluidics inlet/outlet

675 um 6" metallized wafer piece1 cm

uChannel

Hydraulic Temperature Stabilizer @ 37ºC

Microscope system integration

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Microscope system integration

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Patterns for calibration

DNA Origami Nano rulers

Position & Bightness patterns

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(a) Isolation of vital tissue from patient lung(b) Preparing small tissue samples for outgrowth8c) Brightfield Images from isolated cells in 2D culture (mag. 20x, fibroblasts marked by red circles)

Demonstration application

(c )

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Biocompatibility studies

M a D o L L 4 7 5 h o u r s lo n g te r m e x p o s u r e

W a v e le n g th (n m )

Re

lati

ve

Ap

op

tos

is %

940

630

588

525

465

375

Sta

uro

sp

or i

n 1

µM

0

5

1 0

1 5

2 0

2 5

5 0

1 0 0

1 5 0

Phototoxicity

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Biocompatibility studies

Biocompatible materials

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CMOS Avalanche PhotodiodesElectronics

NanoLED arrays

Image proc. and reconstruction

Microsystems for life sciences

Tissues for intra-cell structure obs.

Dissemination and Training

Multiphysics simulations

Ludwig-Maximilians-Universität München

Universitat de Barcelona

Technische UniversitätBraunschweig

Austrian Instituteof Technology

University of Rome

Expert Ymaging SL

MedizinischeUniversität Wien

Swiss FoundationFor Research in Microtechnology

DNA nanorulers

Consortium

Funded by the European Union - GA 737089 34

1. To proof-the-concept of ChipScope by demonstrating microscopy of living tissues with:

• direct imaging with superresolution

• molecular fluorescent imaging with superresolution

• real-time operation (>10 frames per second)

2. To establish the technological basis as well as theoretical understanding of the ChipScope concept:

• realizing highest resolution, separately addressable, nanoLED arrays, pixel sizes <Abbe’s Limit

• integrated with photodetectors with single photon and ns detection capabilities

• developing theoretical background in optical interaction between nanoLED arrays and nano-objects

3. To promote the ChipScope concept in the scientific, the industrial and the social environment:

• disseminating the advantages of ChipScope to a broad scientific community to trigger further applications in multiple fields

• communicating the opportunities offered by ChipScope for business creation and social improvement

• approaching the ChipScope results to decision makers and politicians to facilitate a better use of them.

Conclusions

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An optical microscope on a chip with superresolution capabilities

Conclusions: microscope on a chip

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The ChipScope

project is funded by

the European Union’s

Research

Programme Horizon

2020