Tutorial on Digital Manufacturing

DIGITAL MANUFACTURING
 r
pe
“PDMS road”

pa
CE, EWOD,
etc.

hyd

thr
1994

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Whitesides Biebuyck Quake

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glass
MIMIC
1995 1997 2000

“Digital Manufacturing road”

Today $ • Digital 3D designs

• High-efficiency
PDMS fabrication
• Democratization of
access
MICROFLUIDICS SYSTEMS
FOR ORGAN-ON-A-CHIP
“Integration of several different processes on a single chip to form a system
for sample pretreatment, separation, and detection may allow for new
overall processes, improve efficiency, make possible automation, and
reduce manufacturing costs.”

CMOS culture
Batch processing cost/chip
• Alignment
• Bonding cost/chip
• Manual labor
THE PDMS DOMINATION IN MICROFLUIDICS

PDMS PROPERTIES

• Biocompatible (Implantable)
• Water-impermeable
• Gas-permeable
• Elastomeric
• Transparent
• (Fairly) Inexpensive
• Copyright-free
 Thermoplastics PDMS
Injection molding Soft lithography

 Many cheap replicas  Inexpensive (2D) mold

 The microfluidics illusion
Thermoplastics PDMS
Injection molding Soft lithography

$
$

 Many cheap replicas  Inexpensive (2D) mold

 Expensive (2D) mold  Expensive manual labor

Iteration of (3D) designs is expensive!

 Behind-the-scenes PDMS microfluidics

Picked for
publication
Hmm …
This one for
the art
show
maybe
Don’t show
this to
anyone

Don’t show
this either!
 3-D printed shoes
3-D printed cars

3-D printed buildings

THE 3-D PRINTING REVOLUTION

Art/Design/Food

clothing & jewelry

3D-Printing is now used for manufacturing of parts

• 3D design elements
that would require Chrome-alloy housing
much greater effort approved for use in GE jet
with other engines (1st 3D-Printed
production methods part approved for
aviation)
• Demand-oriented
production is cost-
effective because no BMW’s water
complex tools or pump for race
molds are needed cars
 3-D printed blood vessels 3-D printed bionic ears

3-D printed implants Johns Hopkins & Princeton

ITF - Germany
Siavash Mahdavi
3-D PRINTING FOR PERSONALIZED MEDICINE
3-D printed limbs 3-D printed stem cells 3-D printed tissues

Harvard
U. Edinburgh
 Basic Concepts #1

• 3D-Printing has 10 “efficiency advantages” over

other manufacturing technologies
3D-PRINTING

DIGITAL
MANUFACTURING
 3D-PRINTING
Modular Zero Unsold
3D Design Inventory

Complexity is Zero Lead

Free Time

Variety is Reduced
Free Waste

Finite-Element Assembly-Free
Modeling Fabrication

Exact cost Zero-Skill

projection Fabrication
 3D-PRINTING
Modular
3D Design

GrabCAD.com
 3D-PRINTING
Modular
3D Design

Complexity is
Free
 3D-PRINTING
Modular
3D Design

Complexity is
Free

Variety is
Free
 3D-PRINTING
Modular
3D Design

Complexity is
Free

Variety is Mistakes
Free are cheap!

Finite-Element
Modeling
 3D-PRINTING
Modular
3D Design

Complexity is
Free

Variety is
Free

Finite-Element
Modeling

Exact cost
projection
 3D-PRINTING
Modular
3D Design

Complexity is
Free

Variety is
Free

Finite-Element
Modeling

Exact cost Zero-Skill

projection Fabrication
 3D-PRINTING
Modular
3D Design

Complexity is
Free

Variety is
Free

Finite-Element Assembly-Free
Modeling Fabrication

Exact cost Zero-Skill

projection Fabrication
 3D-PRINTING
Modular Zero Unsold
3D Design Inventory

Complexity is Zero Lead

Free Time
DIGITAL
Variety is Reduced
MANUFACTURING
Free Waste

Finite-Element Assembly-Free
Modeling Fabrication

Exact cost Zero-Skill

projection Fabrication
 Basic Concepts #2

• “3D-Printing” is not a technique

• “3D-Printing” refers to a family of techniques

 multiple materials, high res unsupported cavities, high res

PolyJet/MJM
Stereolithography

two materials, low res, cheap multiple materials, low res

Selective Laser Sintering

Thermoplastic Extrusion
Laser sintering
 Bioresorbable Airway Splint Created with a 3-D Printer

polycaprolactone

Laser sintering

EOS Formiga P100 laser

sintering system

Zopf et al., NEJM 368: 2043 (2013)

 POLYJET
• Inkjet + UV curing
• X,Y resolution: 600 dpi (42 µm/dot)
• Z resolution: 16 µm (1600 dpi)
• Max: 1000 mm (X) x 800 mm (Y) x 500 mm (Z)
• $20K + expensive inks
• Great variety of inks
• Materials properties and biocompatibility are
determined by the ink-binding process
• Concern: FDA approval
POLYJET PRINTING
in
microfluidics
 THERMOPLASTIC EXTRUSION
aka “FUSED DEPOSITION MODELING” (STRATASYS, 1990)

• Invented by Scott Crump (late 1980s)

• Extrusion of thermoplastics through a
nozzle
• X,Y resolution: 100 µm
• Z resolution: 100 µm
• Max: 11 in. (X) x 6 in. (Y) x 6 in. (Z)
• $500 - $2,500
• Extrusion process is well understood
and does not significantly change the
properties or biocompatibility of the
polymers
• FDA-approved polymers
• Hardware and software developments
driven by open-source community
 THERMOPLASTIC EXTRUSION
Afinia H-Series Ultimaker

Makergear M2 Cube

MakerBot Replicator 2
PrintrBot LC
THERMOPLASTIC
EXTRUSION
in
microfluidics
STEREOLITHOGRAPHY
Commercially-available resins
• Yellowing with UV exposure
• Leeching / Cell death
• Proprietary composition
 INSPIRATION FROM TISSUE ENGINEERING

PEG-DA PEG-DA hydrogel PEG-DA-258

monomer (MW > 500) (MW = 258)
light
H2O

acrylate

+
Photo-
initiator

• Hydrated / Porous • Dry / Impermeable

• Soft E= f(M.W.) • E = 100 MPa
• Cell-laden constructs • Cytocompatible

m et al., Lab Chip 6, 1432 (2006)

ademhosseini & Suh
3D-PRINTED PEG-DA-258 IS CYTOCOMPATIBLE
Mouse hippocampal
MW = 258 neurons

PEG-DA
CHO
cells

PEG-DA 100 mm TCPS

Urrios et al., Lab Chip 16: 2287 (2016)
 Rough Smooth

Transparent PEG-DA
prints

+ 0.4% Irgacure-819
Rough Smooth
TMSPMA

UV

SIGMACOTE

UV wavelength
Cesar Parra and Arturo Urrios
Biocompatibility of PEG-DA-258
microchannels
Reduced adsorbption of Nile Red on PEG-DA-258
• Lipophilic stain (MW = 318)
• Used to model drug adsorption
 Basic Concepts #4

• “Bioprinting” refers to the 3D-Printing of

biological material (protein scaffolds, cells) by:
– Stereolithography
– FDM
– Polyjet
– Etc.
Bioprinting
Hydrogel 3D-printing
Volumetric Bioprinting

Miller (2019) Levato (Adv Mater 2019)

Sacrificial
omnidirectional
writing into dense
tissue

Lewis (Sci Adv 2019)

 Advanced SL Concepts #1
 Resolution is often mis-reported
• Resolution of surface features is higher than resolution of
cavity features
 FACTORS THAT AFFECT RESOLUTION IN SL

A resin B

DLP vat

µm
10
• X&Y • Z
– DLP projected pixel size – Absorption of light by the resin
– Diffusion of reactants – Diffusion of reactants
MEANING OF Z RESOLUTION IN STEREOLITHOGRAPHY
 Advanced SL Concepts #2
 Requires manual post-cleaning of the prints
• Technically SL is NOT a fully automated manufacturing
technique
EXAMPLES OF SL IN MICROFLUIDICS
 Advanced SL Concepts #3
 Multi-material printing is possible …
• … but washing away residual resin is difficult
MULTI-MATERIAL SL
Co-printing
PEG-DA 258
build plate substrate
vat
glass
PEGDA 575

1 mm UV light
Water rinse
+
PEG-DA 575

PEGDA 575 1 mm

PEG-DA 258

Long exposure
(channel walls)
1 mm PEG-DA 575

2 mm Rest of the
device
(roof, etc.)
Co-printing of PEG-DA-258 [impermeable] with PEG-DA-700 [porous]

Kim et al., Micromachines 9 :125 (2018)

 Advanced SL Concepts #4
 Choice of photoinitiator+wavelength are crucial for
optimal resolution and biocompatibility
 A D
Molar Extinction Coeff. (M-1.cm-1)

PEG-DA 100 mm
Wavelength Mouse primary neurons
B Rough E

2 mm

C Smooth

CHO cells
 Reducing UV penetration depth
PEG-DA-258

IRG

ITX

~3x increase in absorption at 385 nm

Roof 60 mm
0.4% Irgacure 819
0.1% ITX 200 2 mm
0.2 sec exposure mm 1 mm
Layer
High-resolution XY printing in PEG-
DA-258+ITX

µm
10
Sub-pixel features
High-resolution printing in PEG-DA-
258+ITX
40:1 aspect ratio 27 mm

Kuo et al. (2018), Adv. Mater. Technol.

 3D-printing of 3D microchannels in
PEG-DA-258+ITX

uo et al. (2018), Adv. Mater. Technol.

 Complex 3D microfluidic mixers
Chaotic mixer

1 mm

“Double helix” mixer

Coiled cell sorter

et al., Adv Mater Technol (2018)1 mm 1 mm

Tissue Chips Biosensors

PDMS
Medical
Soft robotics
device
packaging
(gaskets,
connectors)
 Photo-printable PDMS

Photoinitiator
PDMS monomer containing reactive
screening
acrylate side groups

TPO-L

PL-460 blend

PL-610 blend

TPO
+ Irgacure-819
PDMS monomer containing reactive
acrylate end groups Irgacure-651

High solubility
High optical absorption
PDMS is 3D-printable!
SL-printed PDMS

Bhattacharjee et al., Advanced Materials (2018), 180

SL-printed PDMS
SL-printed PDMS
• 200 µm-thick layers
• 25 layers
• Two-monomer resin

3D-Printed PDMS Sylgard 184 (10:1)

Young’s Modulus 410 kPa 360-870 kPa
Elongation at Break 127% 140%
Tensile Strength 0.71 MPa 7.1 MPa
 SL-printed PDMS

500 mm

500 mm

5 mL/hr 5 mL/hr

5 mL/hr
500 mm

charjee et al., Advanced Materials (2018), 1800001.

 Microfluidic
Microfluidics vs. Automation

• Cheap • Slow
• High throughput • Laborious
incremental

significant

• Cheap(er) • Fast
• High(er) throughput • Automated
3D-PRINTED MICROFLUIDIC AUTOMATION
 3D-Printed Membrane Microvalve

1 mm

DmicroCT E
FEM (COMSOL)

F
 Microfluidic Organ-On-a-Chip Systems

$37

A. Au et al., Lab Chip 15, 1934 (2015)

High reproducibility
Modular design
Easy to manufacture
Easy to operate
Low cost
 Bacterial magnetophoresis

Wonjae Lee et al., Scientific Reports 5: 7717 (2014).

SL FACILITATES USER-FRIENDLY INTERFACES
 “Quake-style” valve in PEG-DA-258 (+0.1% ITX)
Open

Closed
300 µm
300 µm
5 Hz

Lee et al., Lab Chip 18: 1207 (2018)

3D-printed valve with COMSOL-matched seat

Pressure 10 mm-thick
valve seat membrane

500 mm

flow
2 mm channel

Valve Seat 300 mm

10 mm

Constrained
Edges Pressure
200 mm
 Making PEG-DA-258 hyperelastic
with additives
10 µm-thick
400 µm 500 µm
membranes
600 µm 700 µm 800 µm
diam.
1 psi

800 µm diam. 800 µm diam.

1 psi 4 psi
 RESOLUTION & COST

DropLit
 XY Resolution: 22 µm
 Z Layer thickness: 10 µm
 $400 + $600 projector
Ilios HD Ray
 XY Resolution: 22 µm
 Z Layer thickness: 6 µm
 4 inks (automated rinses)
 15,000 €

FSL3D
OWL
 XY Resolution: 50 µm
 XY Resolution: 1 µm  Z Layer thickness: 5 µm
 Z Layer thickness: 1 µm  UV LED
 $90,000  $7,500

Carbon3D
 XY Resolution: 1 µm
 Z Layer thickness: 1 µm
 100x speed
 $90,000
 3D-Printed microfluidics publications
y = 18.8 e0.58x

Machines are more

efficient and precise at
manufacturing than a
human
y = 16.6 e0.5x

Manz Whitesides Biebuyck Quake Toner Whitesides

Science 1993 Nature 1995 Science 1997 Science 2000 Nature 2007 Anal. Chem. 2008
CITED

1,386 652 535 2,222 1,628 670

 g el
o
ydr
glass “PDMS road” h

pa
p

thr
er

ea
d
“Digital Manufacturing road”
low throughput
2016
2019

“Injection Molding road”

$ $
high cost