Lateral Flow Production Strategies

Serve Science Co., Ltd.

 Typical Test Structure
Plastic Cover

Absorbent

Plastic Backing

Control Reagent

Test Reagent

Membrane with/without
Blocking Reagent

Conjugate Pad
with Reagent

Absorbent Pad
Sample Flow Serve Science Co., Ltd.
 Outline of manufacturing process
Membrane Conjugate Pad Sample Pad

Stripe test and control lines Pre-treat pad Pre-treat pad

Block membrane if necessary Stripe / dip and dry pad

Assemble membrane, conjugate pad, sample pad, wick and backing into cards

Cut cards into strips

Assemble strips into cassettes

Package cassettes Serve Science Co., Ltd.

 Summary of Manufacturing Processes
Reagent Application

Drying Process

Lamination of Components

Inspection/Marking

Cutting

Quality Control

Assembly/Packaging
Serve Science Co., Ltd.
 PRODUCTION SCENARIOS

BATCH FORMAT

VERSUS

CONTINUOUS WEB / IN-LINE FORMAT

Serve Science Co., Ltd.

 Batch vs. Continuous Processing
Batch
▪ Strip format for material and
lamination: 150 - 500 mm strip
length
▪ Process strips in groups
▪ Process time is non-critical
▪ Poor process symmetry
▪ Low to medium production
R&D to 3-6 million tests per
year
▪ High labor content
Continuous
▪ Roll format for material and
laminate: 50-100 meter roll length
▪ Rolls used for continuous process
▪ Process time is critical and limited
by web speed and equipment size
▪ Excellent process symmetry
▪ Medium to high volume
~ 4 million to + 1 billion pieces per
year
▪ Low labor content
Serve Science Co., Ltd.
 Serve Science Co., Ltd.
Batch Process
Reagent Application: Test/Control: XYZ Table Dispenser
Conjugates: XYZ Table Dispenser
Coat: Dip Tank
Inspection: Manual with tracking function
Dry: Oven
Lamination: Manual with tooling fixtures
Inspection: Manual with tooling fixtures
Cutting: Guillotine
Rotary
Assembly (Plastic Housing): Manual with tooling fixtures or semiautomatic
machine
QC: Off-line with test equipment
Packaging: Use of pre formed pouches with manual or
automatic filling of pouches and sealing
 Serve Science Co., Ltd.

Batch Manufacturing Equipment

XYZ 3000 dispenser with BioJets and AirJets Manual Dip Tray

Clamshell benchtop laminator CM 4000 Guillotine Cutter

 Serve Science Co., Ltd.
Batch Process Line Layout
XYZ XYZ Dip Tank Oven

T/C Conjugate Inspect/Mark Block Dry

Cutter Clamshell Clamshell

Cut/Sort Inspect/Mark Laminate cover Laminate Master Strip

Assembly Roller

Typ. 1.5 million tests limited

Assemble Assemble Assemble by assembly & pouching
12-15 + operators
Increase to 4-6 million
Seal Seal by adding pouching
Seal and/or assembly
machine
Final QC
 Serve Science Co., Ltd.
Continuous Process
Reagent Application: Test/Control: Reel-to-Reel Dispenser
Conjugate: Reel-to-Reel Dispenser or Diptank
Coat: Reel-to-Reel Dispenser or Diptank
Dry: In-line dry process on Reel-to-Reel Equipment
Inspection/Mark: In-line on Reel-to-Reel Equipment
Lamination: In-line on Auto Laminator Equipment
Cutting: Integrated into assembly/pouching machine
Assembly: Cut and place test strip into housing,
automatic reject of bad parts
Packaging: Roll feed foil with automatic pouch form, fill and seal

Bottling: Cut, collect and place into bottle, and feed of bottle,
capping and labeling
 Serve Science Co., Ltd.
In-line manufacturing equipment
Reel-to-reel web handling and dispensing platform

Auto Laminator
 Continuous Process Layout
Reel-to-Reel Dispense with Coat/Dry Reel-to-Reel Dispense with Dry

T/C, Block, Dry, Inspect/Mark Conjugate

Cut/Bottle Laminate/Inspect/Mark

2 parts/sec.
Typ. 10 tests/sec.
60 million +
Package Cut/Assemble
tests per year.

Operators—2-5

Package Cut/Assemble

Serve Science Co., Ltd.

Key processes and equipment
1) Reagent Application
2) Drying Process
3) Lamination of Components
4) Cutting
5) Inspection /Quality Control
6) Assembly/Packaging
7) Packaging

Serve Science Co., Ltd.

 1) Reagent Application
XYZ Motion Table (small volume production) BATCH
- Dispensing * Test/Control
* Conjugate
Dip Tray/Impregnation
-Coating * Conjugate
* Blocking/Others
Reel-to-Reel (large volume production)
- Dispensing * Test/Control
* Conjugate
* Blocking/Others
- Coating * Conjugate
* Blocking/Others CONT.

Serve Science Co., Ltd.

XYZ3000 Dispensing Platform

Serve Science Co., Ltd.

ZX1000 Platform with Frontline Dispensers

Serve Science Co., Ltd.

 Serve Science Co., Ltd.
Dip Tray: Batch Process

Issues: Soak Time: Chemistry concentration stability with repeated dip

Drying: Chemistry migration effects
Material: Material inconsistencies
 Serve Science Co., Ltd.

Reel-to-Reel Web Handling Module

 Serve Science Co., Ltd.
Dip-Tank on the Reel-to-Reel Web Handling Module
Dispensing Platform
on the Reel-to-Reel
Web Handling
Module

Serve Science Co., Ltd.

 Serve Science Co., Ltd.

Material Tracking / Reel-to-Reel Web Handling Module

 Reagent Application Issues for Continuous Processing

1. Process Dwell Times

- Limited coating times
Low web speeds decrease throughput

2. Bending Stresses
- Membranes, absorbents, other pad materials
with low mechanical strengths when wet

3. Material Availability
- Absorbents and other materials may not be
available in roll formats

Serve Science Co., Ltd.

 2) Drying Process

BATCH
Batch Drying
Convection Oven –

Continuous Drying
Vertical Tower—Reel to Reel Web Handling

Horizontal Tunnel – Conveyor or Web System

CONT.

Serve Science Co., Ltd.

 Serve Science Co., Ltd.
Drying Process

Air Temperature
Temperature

Dry End Point

Primary Dry Secondary Dry

(Evaporation) (Desorption)

Time Temperature and

water loading determines end point time
Drying: Batch Process
IR Sensor

Air Flow

Serve Science Co., Ltd.

Convection Drying Oven

Serve Science Co., Ltd.

Drying: Continuous

Web
Exhaust Air
with moisture

Air Air normal to surface

Web Temperature Monitoring

To Take Up

Serve Science Co., Ltd.

 Serve Science Co., Ltd.
Vertical Tower(s)
 Serve Science Co., Ltd.

Horizontal Tunnel
 Drying Issues for Continuous Processing

1. Process Dwell Times

- May require long times/slow speeds.
This limits throughput.

2. Bending Stresses
- Membranes, absorbents, other pad materials
with low mechanical strength

Serve Science Co., Ltd.

3) Lamination of Components

Batch/Lamination Table BATCH

- Uses strip and roll format

Semi-Automated/ Clamshell Laminator

- Use precision cut strips of materials
- Design for lamination (chamber, curl, etc.)

Semi-continuous/Continuous
- Uses strips and roll format combinations CONT.

Serve Science Co., Ltd.

Clamshell Laminator

Serve Science Co., Ltd.

 Serve Science Co., Ltd.

Sample Lamination Machine Configuration

Sample Lamination Machine with environmental enclosure

Serve Science Co., Ltd.

Lamination Issues for Continuous Processing
Bending Stresses
- Membranes, absorbents, other pad materials and
adhesives may have limited mechanical strength
- Thick plastic backing and thick structure sets up layer
stresses and can cause delamination during processing
- Test design and materials selection may not permit bending
after lamination

Serve Science Co., Ltd.

 4) Cutting BATCH
Guillotine
- Programmable width down to 1 mm
- Speed up to 240 parts / minute
- Recognize and reject bad parts
- Count and collect parts for bottling

Slitting - For conjugate pad

Rotary
- Set width
- Minimum width 4-5 mm
- Speed up to + 350 parts / minute
- Need to sort bad parts CONT.
Cut and Place
- Interface with automation assembly
- Sense / reject of bad parts
- Precision placement of parts
Serve Science Co., Ltd.
 Serve Science Co., Ltd.

Guillotine Cutting Module

 Serve Science Co., Ltd.

Sheet Slitting Module

Rotary Cutter and Slitter

Serve Science Co., Ltd.

Cut and Place with Rejection of Bad Parts

Serve Science Co., Ltd.

Cut and Place
 Cutting Issues for Continuous Processing

1. Materials
- Adhesives may build up on cutting surfaces
- Thick plastic backing may dull blades quickly
- Test design and materials chosen may not hold up well
under cutting stresses

2. Sorting of Good/Bad parts

- Need the ability to reliably remove bad parts at some point
in process

Serve Science Co., Ltd.

5) Inspection /Quality Control
Test/Control Dispense
- Optical Sensor -> Inspect only presence of solvent line
- UV Light Box -> Presence and width of solvent/reagent line
- Vision Camera ->Presence and width of solvent line
Conjugate
- Visual
- Optical
Lamination/Material Defect
- Visual
- Optical transfer “bad” mark BATCH
Batch Process
- Visual
- Manual workstation with UV Light box
Continuous Process
- Optical Sensor
- In-Line camera/Light box CONT.
Optical Sensor Inspection and Marking

Serve Science Co., Ltd.

Continuous Process

Serve Science Co., Ltd.

Final QC - Test Strip Reader

Serve Science Co., Ltd.

 Serve Science Co., Ltd.

Sample Test Strip Reader Data Report

 Serve Science Co., Ltd.

Sample Test Strip Reader Data Report

 6) Assembly/Packaging

Assembly into Plastic Housing BATCH

Manual Process -
Assembly Roller
Press

Automated -
Integrated cut and place of test strips
-- Multiple-up for higher throughput CONT.
-- Options for pad printing and
ultrasonic bonding
-- QC integrated

Serve Science Co., Ltd.

Assembly Roller

Serve Science Co., Ltd.

Automated Assembly System

Serve Science Co., Ltd.

Automated Assembly Station with multiples for higher
throughput

Serve Science Co., Ltd.

Automated Assembly Station with bowl feeding

Serve Science Co., Ltd.

7) Packaging
Simple Sealer
- Use preformed pouches BATCH
- Manual load of parts in pouches
- Semi-automatic seal

In-Line Sealer
- Use roll stock
- Manual or automatic load of parts
in pouches
- Automatic seal / cut
- Reduced material cost using roll stock CONT.

Serve Science Co., Ltd.

 Serve Science Co., Ltd.

ISSUES TO REMEMBER

▪ The ultimate goal is sustainable, scalable long term production and

profit
▪ The equipment, materials and reagents chosen, as well as the
processes designed and transferred from R&D will dictate the
viability of the product
▪ Utilize design control methods as early in the development process
as possible. Involve personnel from production, marketing, and QC
in the R&D process from the start
▪ Design processes that can be easily scaled up. Concentrate on
dispensing and drying processes and on final assembly processes
▪ Carefully evaluate automation costs for the processes designed
early in the process
▪ Utilize equipment and processes that can be readily validated