ALTIUMLIVECHALLENGES IN THE DESIGN OF LAB-ON-PCB PLATFORMS

Despina MoschouLecturer (Assistant Professor)Electronic and Electrical EngineeringC3Bio, University of Bath, UK

Munich16th January 2019

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Outline

2 Lab-on-Chip technology

Lab-on-PCB?

Current design approaches

Current challenges

Next steps

1 Who we are?

Bath, UK

University of Bath

C3Bio: Centre for Biosensors, Bioelectronics and Biodevices

Multidisciplinary research centre established in March 2018

• 15 core academics

• 18 affiliated academics

• 10 postdocs

• ~30 PhD students

Faculty of Engineering & Design

Faculty of Science Faculty of Humanities & Social Sciences

Chemical Engineering Biology & Biochemistry Health

Electronic & Electrical Engineering Chemistry Psychology

Mechanical Engineering Computer Science

Pharmacy & Pharmacology

Physics

https://www.bath.ac.uk/research-centres/centre-for-biosensors-bioelectronics-and-biodevices/

Dr Pedro EstrelaDirector

Prof Chris FrostDeputy Director

@C3Bio_Bath

Research Mission

Research mission:

• develop technology that improves biomedical diagnosis,

environmental monitoring, industrial bioprocesses and scientific

understanding of biological functions

• bridge the gap between different disciplines converging into fit-for-

purpose devices

• achieve real-life impact with its research, addressing specific clinical,

environmental and industrial needs

end-user engagement | multidisciplinary training

Lab-on-Chip

Trend for smarter multi-functional microchips → μTAS (micro Total Analysis Systems) aka LoC (Lab-on-a-Chip)= Systems of reduced size and weight, performing sample handling steps together with analytical measurements

Manz et al., “Miniaturized total chemical analysis systems: A novel concept for chemical sensing”, Sensors and Actuators B: Chemical, vol 1, 1990, 244-248; A. Tudos et al. , Lab on a Chip, 2001, 1, 83-95

∝Microfluidic components:μfluidic channels Chem/bio detectors/sensorsμvalves separatorsμpumps μmixers+ …….

IC Components:Transistors DiodesCapacitors Inductors+ …………..

Democratize healthcare for everybodyIn one sentence: We can clearly expect lab-on-a-chip to save numerous lives.

New, cross-disciplinary field

MicroelectronicsMicroscale fluid

mechanics

Biochemistry

Microfabrication

Chemistry-surface modifications

Biology/medicine

Lab-on-Chip impact

• Unique advantages:• Miniaturization• Low reagent volumes• Rapid analysis time• Early detection• Automation/portability

Whitesides G.., “The origins and the future of microfluidics”, Nature, vol 442, 2006, 368-373Volpatti et al, “Commercialization of microfluidic devices”, Trends in Biotechnology July 2014, Vol. 32, No. 7

• Indicative applications:• Point-of-Care medical diagnostics• Environmental monitoring• Defence/security• Food safety• Regenerative medicine• Chemical synthesis• Drug screening/discovery• ………

• LoC market:• 2013 valued @ $1.6 billion• Expected CAGR: 18-29%• 2018 market size: $3.6–5.7 billion• Mainly attributed to diagnostics• Start-up scene booming

Lab-on-Chip components

separators

μmixers

Chem-bio detectors/sensors

μfluidic channelsμvalves

μpumps

Integration

CMOS Glass Polymers Paper

Semiconductor fabrication techniques

Well-known Cost-effective Cost-effective

Sophisticated circuits Transparent, biocompatible

Easy polymer processing Printable

Commercialized components

Commercialized components

Elastic, flexible, transparent, biocompatible, versatile

Stackable, filtering

μfluidics integration Electronics integration Electronics integration Few μfluidics demonstrated

Overall cost Expensive Mass-manufacturing? Detection sensitivity

INTEGRATION

Lab-on-PCB

• First suggested in the ‘90s, however side-lined by easier microfluidic fabrication processes (soft lithography, glass/polymer processing)

• Recently LOC integration main focus → PCBs ideal integration platform:

• Long-standing industrial infrastructure (low-cost upscaling)• Adequate microfabrication capabilities• Intuitive integration of electronics

Moschou D and Tserepi A., “The Lab-on-PCB approach: Tackling the μTAS commercial upscaling bottleneck”, Lab on a Chip, 2017,17, 1388-1405

IoT eraCooling applications

MF MANUFACTURING: EUROPEAN INITIATIVE FOR THE STANDARDIZATION AND MANUFACTURABILITY OF COMPLEX MICROFLUIDIC DEVICESUNIVERSITY OF TWENTE, MESA+

DNA amplification Lab-on-PCB

Moschou et al., Sensors and Actuators B: Chemical, vol 199, 2014, 470-478; Moschou et al., Proc SPIE 8765, 2013, 87650L; Jolly et al, Biosensors and Bioelectronics 123, 244-250

PCB biosensors

Tseng H.-Y. et al., Development of an electrochemical biosensor array for quantitative polymerase chain reaction utilizing three-metal printed circuit board technology, Sensors and Actuators B: Chemical, Volume 204, 1 December2014, Pages 459–466Pu Z. et al., A flexible electrochemical glucose sensor with composite nanostructured surface of the working electrode, Sensors and Actuators B: Chemical, Volume 230, July 2016, Pages 801–809Li X. et al., Simultaneous detection of lactate and glucose by integrated printed circuit board based array sensing chip, Analytica Chimica Acta, Volume 771, 10 April 2013, Pages 102–107

DNA sensors

Flexible glucose sensors

Lactate and glucose sensors

First upscaling efforts

Inlet

Prototyped PCB reference electrodes Prototyped 3-layer PCB microfluidics

ReferenceelectrodesLayer#1:(Ag/AgCl)

SensingelectrodesLayer #2: (Au)

MicrofluidicsLayer #3

Moschou et al., Sensors 2015, 15(8), 18102-18113.Moschou et al., Biosensors and Bioelectronics, 2016, 86, 805-810.Moschou et al, mTAS 2016, Dublin, Ireland, 9-13 October 2016.

ELISA Lab-on-PCB

Layer #1

Layer #2

Layer #3

LODcolorimetry=28.22pg/mLLODamperometry=126.75pg/mL

Optical detection Electrochemical detection

IFN-γ recovery(Tuberculosis biomarker) in human serum

10 100 1000-1

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IFN-γ concentration (pg/mL)

1000 10000TREM-1 concentration (pg/mL)

10 100 1000

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Amperometry

Abso

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IFN-γ concentration (pg/mL)

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Nominal Colorimetry Sensor0

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10 100 1000-0.06-0.04-0.020.000.020.040.060.080.100.120.140.160.180.20

IFN-γ TREM-1

Absr

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IFN-γ concentration (pg/mL)

1000 10000TREM-1 concentration (pg/mL)

DNA electrochemical PCB-based biosensors

Jolly et al., Biosensors and Bioelectronics 123, 244-250Jolly et al, NanobBiotech conference, 13-15/11/2017, Montreux, Switzerland

Sensing electrode surface characteristics

Soft gold Hard gold

Figure S1. Atomic Force Microscopy (AFM) 3D images of soft and hard gold PCB electrode surfaces.

Figure S3. Relative chemical composition of soft and hard gold PCB electrodes before (BC) and after (AC) Piranha cleaning, comparing a) gold vs organic film and b) gold vs copper, as derived by X-ray photoelectron spectroscopy (XPS) analysis of the surfaces.

The CHIRP project

• Increasing sugar consumption → global diabetes epidemic• Diabetes prevalence rapidly increasing in low/middle-income

countries (Turkey: 13.6%, double the global average)• Turkey: increased childhood obesity, very young population (0-

14 year olds: 25.5% of population)• CHIRP vision: make a pre-diabetes diagnostic test for mass

population preventative screening of children• Painless, reliable, disposable patch

Currently available solutions for diabetes screening

• Low-cost, but invasive

Non-invasive, high-cost

Non-invasive, disposable???

CHIRP project

CHIRP concept

4 partners (UK-Turkey)2 year projectProject budget: £279,898.86

Passive PCB microfluidics

• Hydrogel microneedle array for ISF extraction• Attachment on flexible Lab-on-PCB platform• Plasma treated, hydrophilic microfluidics to extract sample from microneedlesVasilakis, N., Moschou, D. et al, 2016. Long-lasting FR-4 surface hydrophilisation towards commercial PCB passive microfluidics. Applied Surface Science, 368, pp. 69-75.

Flexible PCB sensing platform

D. Moschou et al, "A PCB-based electrochemical glucose biosensing platform," in 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS 2016), Dublin, Ireland, 2016, pp. 1047-1048.Y. Zhong, T. Shi, Z. Liu, S. Cheng, Y. Huang, X. Tao, et al., "Ultrasensitive non-enzymatic glucose sensors based on different copper oxide nanostructures by in-situ growth,“ Sensors and Actuators B: Chemical, vol. 236, pp. 326-333, 2016.

• In situ growth on Cu electrodes

• Inkjet printing of CuOnanoparticles on gold plated electrodes

Indicative ongoing projects

Infectious disease andantimicrobial resistance diagnosisfor low and middle incomeeconomies

Inkjet printed BioFETbiosensors

Brain-on-Chi

Biofuel cells

Challenges & next steps

• Challenges:• Unconventional structures: custom - made stack file accompanying Gerber files• Microfluidic geometries more curved as opposed to corners in electronic design: time

consuming design process• No design rules for Lab-on-PCB devices yet• No standard process for fluidically tight cavities across PCB manufacturers• Still Lab-on-PCB not well-known across industry

• Next steps:• New custom-made stacks with advanced Altium stack manager capabilities• Exploitation of Draftsman documents and cavity creation with Altium tools• Creation of microfluidic component libraries in Altium• Work with manufacturers globally to identify optimum processes• Further dissemination of Lab-on-PCB technology• Workshops, summer schools, textbook for Lab-on-PCB designers

Embedded component Altium capability

Industrial engagement

EIPC Summer Conference Edinburgh Global PCB market and local manufacturing: “Strategies to maintain profitability in the European PCB Industry”Date: June 9 & 10, 2016

PCB BioMEMsWorkshops in UK

Many european academic groups working on PCB-based prototypes…

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Conclusions

1 Lab-on-Chip technology: future of personalized healthcare devices

Lab-on-PCB: ideal integration platform for mass manufacturing

Altium capabilities enable CAD design of such devices

Unconventional PCB design and stacks for Lab-on-PCB applications

Future improvements:Exploitation of draftsman capabilitiesCustom stack definitionExploitation of mechanical cavity design functionsLibraries for microfluidic components

Acknowledgementshttps://www.bath.ac.uk/research-centres/centre-for-biosensors-bioelectronics-and-biodevices/

Thank you!

Questions?

E-mail: D.Moschou@bath.ac.uk