Synthesis Protocol & Scale-Up

From benchtop validation to pilot manufacturing — protocols, cost model, environmental footprint, and sensitivity drivers.

Synthesis Protocol

Benchtop

GRAM SCALE

1–10 G / BATCH

1
Pre-dry feedstock
Dry native feedstock at 60°C for 24h to reduce moisture to <5 wt%
2
Weigh reagents
Combine feedstock and CHPTAC at target molar ratio in a 50 mL stainless steel grinding jar
3
Add grinding media
Load stainless steel balls at target ball-to-powder ratio (BPR)
4
Seal and mill
Mill at target frequency (20–50 Hz) for target duration (10–120 min) in a planetary ball mill
5
Recover product
Remove jar, allow to cool to room temperature (5 min)
6
Purify (optional)
Wash with ethanol/water (70:30 v/v) to remove unreacted reagent; centrifuge; dry at 50°C
7
Characterise
Measure DS by elemental analysis or potentiometric titration; particle size by laser diffraction; zeta potential by DLS

Pilot

KILOGRAM SCALE

10–100 KG / BATCH

1
Bulk pre-dry
Dry feedstock in a tray dryer at 60°C for 48h
2
Weigh and blend
Blend feedstock and CHPTAC in a ribbon blender to ensure homogeneous premix before milling
3
Load pilot mill
Transfer premix and grinding media into a 10–50 L planetary or continuous vibratory ball mill; confirm BPR
4
Mill
Run at scaled frequency and duration per established benchtop-to-pilot transfer parameters; monitor jar temperature with external IR sensor
5
Discharge and sieve
Discharge product through a 500 µm sieve to remove grinding media fines
6
Purify
Wash in a stirred tank with ethanol/water; filter on a drum filter; dry in a fluidised bed dryer at 50°C
7
QC sampling
Sample at multiple points per batch; measure DS, D50, moisture, and zeta potential; compare against specification

Scale Comparison

Parameter	Benchtop	Pilot
Batch size	1–10 g	10–100 kg
Mill type	Planetary ball mill	Pilot planetary / vibratory
Milling volume	50–500 mL jar	10–50 L vessel
Typical cycle time	30–120 min	60–180 min
Energy consumption	8–18 kWh/kg	5–12 kWh/kg
DS range achievable	0.05–0.70	0.05–0.65
Purification	Ethanol wash + centrifuge	Drum filtration + FBD

Technoeconomic Analysis

Costs derived from current process conditions (CHPTAC, ratio 0.50, 25 Hz, 60 min)

Cost per kg product (€/kg)

Raw feedstockCHPTACMilling energyLabour & overheadsPurification

Pilot component breakdown

Component	€/kg	% of total
Raw feedstock	€0.45	10.7%
CHPTAC	€1.40	33.4%
Milling energy	€1.43	34.0%
Labour & overheads	€0.54	12.9%
Purification	€0.38	9.1%
Total	€4.20	100%

Life Cycle Assessment · Cradle to Gate

Global Warming Potentialkg CO₂eq / kg

Mechanochemical−49% vs conventional2.34

Conventional wet4.6

Cumulative Energy DemandMJ / kg

Mechanochemical−35% vs conventional67.8

Conventional wet105

Water ConsumptionL / kg

Mechanochemical−77% vs conventional48.5

Conventional wet210

GWP

"Dominant contributor: Milling energy (1.28 kg CO₂eq/kg)."

Energy

"Dominant contributor: Drying (27.0 MJ/kg)."

Water

"Dominant contributor: Purification wash (32.0 L/kg)."

Sensitivity · Cost Calculator

Baseline cost · derived from current process conditions (CHPTAC, ratio 0.50, 25 Hz, 60 min)

Benchtop

€8.81/kg

Baseline from process conditions

Pilot

€4.20/kg

Baseline from process conditions

Sensitivity · % deviation from baseline

← cost reduction opportunity · cost increase risk →

Reagent price0%

−30%0+30%

± on reagent cost

Energy cost0%

−30%0+30%

± on milling energy

Feedstock price0%

−30%0+30%

± on raw feedstock

Yield loss / DS shortfall0%

−30%0+30%

± efficiency penalty on reagent + energy

Production volume0%

−30%0+30%

± on labour & overheads only

Higher volume reduces cost via economies of scale

Benchtop · adjusted

€8.81/kg

Pilot · adjusted

€4.20/kg