Developments in Micro-GC:

Theory and Practice

Robert E. Synovec Associate Chair, Graduate Program

Faculty Director, CPAC

Department of Chemistry, Box 351700

University of Washington

Seattle, WA 98195

Email: synovec@chem.washington.edu

CPAC GC Workshop, Seattle, WA

October 31, 2010

OUTLINE

• 1D Separations and Extra-Column

Peak Broadening

• Recent Modeling for High Speed

Temperature Programmed GC

• Recent Examples with Bench-Top GC and

State-of-the-art GC-on-a-chip

Micro - GC • Fast analysis times…sub-minute to sub-

second… “GC sensor”

• Optimize chemical information per time…. …..Optimize total peak capacity & peak capacity production

– Minimize extra-column peak broadening with analyzer

design

– Implement high speed temperature programming

1D Peak Capacity Definitions

1nc,1D =

1t

1wb

1 1nc,1D

1t 1wb

=

Peak Capacity for a 1D separation @ Rs=1:

Peak Capacity Production* for a 1D separation:

* X. Wang, D. R. Stoll, P. W. Carr, P. J. Schoenmakers, J. Chromatogr. A, 2006, 1125, 177-181

Peaks resolved per separation time

Total number peaks ideally resolved

0 1 2 3

Time (s) Time (s)

0 1 2 3

0

2

4

6

8

10

0 10 20 30

0

20

40

60

80

100

Rela

tive S

ignal (%

) Isothermal (left) versus Temperature Programmed (right) for 1 meter, 100 micron ID column (simulated from real isothermal data)

Unit resolution for adjacent peaks, with constant peak capacity nc = 40

nc / t = 80 per minute nc / t = 800 per minute

Theory Behind Band Broadening Minimization

Plate Height (H): index describing the rate of band broadening along the separation path

eg xtsH= + +u C u+HB

Cu

2 22g,o c f

2 2g,o s

2D jf d uf 2k'd u1+6k'+11k'H= + +

u D j96(1+k') 3(1+k') D

Golay Equation:

Injection Detection Electronics

Dead Volumes

Longitudinal Diffusion

Resistance to Mass Transfer – Mobile Phase

Resistance to Mass Transfer – Stationary Phase

Hcolumn u: average linear velocity of mobile phase

Short Column: Theoretical H vs. ū

0

50

100

150

200

250

0 200 400 600 800 1000 1200

ū, average linear flow velocity (cm/s)

H (m

m)

ūopt = (192)1/2Dg,o j / dc

1 m x 100 mm i.d. column, H2 , 150 °C, Dg,o = 0.6 cm2/s, k’ = 0

Hmin , ūopt

g s exB

H= +C u+C u+Hu

Theory Behind Band Broadening Minimization

2 22g,o c f

2 2g,o s

2D jf d uf 2k'd u1+6k'+11k'H= + +

u D j96(1+k') 3(1+k') D

1/22 3 2 2 2

g,o o c o f ob 2

g,o s

2D jf(1+k') t (1+6k'+11k' )d ft 2k'd tw = 4 + +

L 96D j 3D

Peak Width Detected:

Golay Equation Limited:

Injection

Detection

Electronics

Dead Volumes

1

10

102

103

104

10 100 1000 ū (cm/s)

wb (

mill

iseconds) = Hmin, ūopt

Big challenge for instrumentation development Need to reduce extra-column band broadening from injection, detection, electronics and dead volumes

Peak width ~ a few ms

Theoretical wb vs. ū (for 1 m column)

Dg,o = 0.6 cm2/s, k’ = 0, 100 mm i.d. column, H2 , 150 °C

GC Sensor: Synchronized Dual-Valve Injection

C

Time, milliseconds

C

0 100 200 300 400

0

1

2

3

FID

Sig

na

l, v

olt

s

G.M. Gross, B.J. Prazen, J.W. Grate, R.E. Synovec, Anal. Chem. 76, 2004, 3517 - 3524.

Separation conditions (1 m x 100 micron) •

KEY….Dual-valve based injection (2.5 ms) •

• 7 component mixture injected (retention order: methanol, benzene, octane,

chlorobenzene,anisole, decane, butylbenzene)

Wb = 5 ms

k’ = 0

Modeling Bigger Picture: wb@opt (at Hmin, ūopt) vs. L (and dc)

V. R. Reid and R. E. Synovec, Talanta, 2008, 76, 703-717.

0.1

1

10

100

1000

10 100 1000 10000 L (cm)

wb

@o

pt (m

s) 50 mm

100 mm

180 mm

250 mm

320 mm

530 mm

k = 0, Dg,o = 0.6 cm2/s, h = 1.135 x 10-5 Pa*s,

Po = 1 atm (101325 Pa), H2 carrier gas, 150 °C

Synchronized Dual-Valve Injection

High-Speed FID

Hext 0

Various dc

Hcolumn only

Bigger Picture: wb@opt (at Hmin, ūopt) vs. L (and dc)

V. R. Reid and R. E. Synovec, Talanta, 2008, 76, 703-717.

0.1

1

10

100

1000

10 100 1000 10000 L (cm)

wb

@o

pt (m

s) 50 mm

100 mm

180 mm

250 mm

320 mm

530 mm

k = 0, Dg,o = 0.6 cm2/s, h = 1.135 x 10-5 Pa*s,

Po = 1 atm (101325 Pa), H2 carrier gas, 150 °C

How does standard practice of GC compare ?

Hext 0 Various dc

Hcolumn only

0 5 10

0.2

0.4

0.6

0.8

1.0

1.2

Separation in ~ 14 minutes >2 second wide peaks

Retention Time, min

Sign

al (

FID

, arb

. Un

its)

Typical GC Separation of Gasoline

Zoom – in of box section

658 660 662 664 666 668

0.5

1.0

1.5

Retention Time, seconds

Sig

nal (F

ID, arb

. u

nit

s)

~ 2 s

nc / t 30 peaks/min 10 min for nc ~ 300

wb@opt (at ūopt) vs. L

0.1

1

10

100

1000

10 100 1000 10000 L (cm)

wb

@o

pt (m

s) 50 mm

100 mm

180 mm

250 mm

320 mm

530 mm

Standard Auto-injection / FID or MSD

Peak widths 2 s or more are typical !!

wb@opt (at Hmin, ūopt) vs. L

0.1

1

10

100

1000

10 100 1000 10000 L (cm)

wb

@o

pt (m

s) 50 mm

100 mm

180 mm

250 mm

320 mm

530 mm

Standard Auto-injection / FID or MSD

Peak widths 2 s or more…..

40 m

180 mm

Wb ~ 300 ms possible

4 Component Mixture…with Auto-Injection only (Methanol, Anisole, Octanol, Tridecane Mixture)

80 120 160 200 240

0

1

2

3

4

5

Time (s)

FID

Re

sp

on

se

(V

)

200:1 split, average Wb= 1.6 s

86 90 Time (s)

M A O T

M

245 251 Time (s)

T

nc / t ~ 36 peaks/min

… 8.3 min for 300 peaks

Column: 40 m x 180 mm ID, Rtx-5 0.4 mm film

Oven: 90-250°C @ 40°C/min

Flow Conditions: Constant Flow, 1.3 ml/min

4 Component Mixture – High Speed GC Capillary: 40 m x 180 mm ID, Rtx-5 0.4 mm film Temperature Program: 90-200°C @ 40°C/min

Injection: 15 ms pulse (modified auto-injection) Flow Conditions: pressure ramp 85-115 psi @17.5 psi/min

Time (s) 50 100 150 200

0

1

2

3

4

FID

Response (

V)

43.1 43.5 43.9 0

2

4

250 ms

187 188.5 190

0

0.2

0.4

750 ms

M

A

O

T

Dead Time Optimized Separation

Consistent

With

Theory!

4 Component Mixture – High Speed GC

nc / t 120 peaks/min … 2.5 min for 300 peaks

Capillary: 40 m x 180 mm ID, Rtx-5 0.4 mm film

Temperature Program: 90-210°C @ 40°C/min

Injection: 20 ms (modified auto-injection)

Flow Conditions: pressure ramp 30-100 psig @17.5 psi/min (1.2 – 5.5 mL/min)

100 150 200

0

0.5

1

1.5

2

Time (s)

FID

Response (

V)

81.6 82.0 82.4

0

0.2

0.4

0.6

203.8 204.2 204.6 205

0

0.04

0.08

0.12

450 ms

500 ms

M

A

O

T

M T

Gasoline – High Speed GC

1

1.5 2 2.5 3 0

2

3

4

Time (min)

FID

Response (

V)

Wb= 480 ms

Wb=540 ms

1 s

Capillary: 40 m x 180 mm ID, Rtx-5 0.4 mm film

Temperature Program: 90-210°C @ 40°C/min

Injection: 50 ms pulse (modified auto-injection)

Flow Conditions: constant flow rate using 45-115 psi @17.5 psi/min

High Speed GC with Temperature Programming

at Hmin and uopt

• 100 mm i.d. column as function of column length, L,

… in limit that all peak broadening is due to column only (no Hex)

• Synchronize carrier gas flowrate and temperature programming rate

so all analytes elute with a k’ 0 ….at moment leaving column

• Model analyte boiling point range such that all elute in temperature

program from 50 oC to 350 oC (“typical” van’t Hoff plot applied)

MODELING SOFTWARE DESIGN AND OUTPUTS

• Temperature Programming Rates

• Separation Run Times

• Peak Widths ~ Constant ( ~ unretained peak)

• Pressure Required

• Total Peak Capacity

• Peak Capacity Production Rates

OUTPUTS

T-Prog Modeling Results Overview

Column Length (m) @ 100 mm i.d.

Temp Program Rate (K/min)

Run time (ms)

Dead time (ms)

Peak width (ms)

Maximum Pressure (psia)

Total peak capacity (nc)

Peak capacity production (nc/t) (1/s)

0.1 1 10

380,000 21,000 780

25 84 271

535 100 12

20 44 130

1.4 7 64

14 230 6000

50 840 23,300

Agilent LTM

Software programmable temperature rates

External column heating allows valve and transfer lines to be heated to inlet temperatures

Quoted ramp rates up to 1800 °C/min

Should cover 300 °C in 10 s

23

10 Component Mixture (C6 – C15) Capillary: 20 m x 180 mm ID, DB-5 0.4 mm film Temperature Program: 75-325°C @ 250°C/min Flow Conditions: 75 - 115 psia @ 40 psi/min

0 5 10 15 20 25 30 35 40 45 50

0

1000

2000

3000

4000

5000

6000

7000

8000

Time (s)

FID

Res

po

nse

(p

A)

14.6 15.0

140 ms

300 ms

Gasoline – High Speed GC Capillary: 20 m x 180 mm ID, DB-5 0.4 mm film Temperature Program: 75-325°C @ 250°C/min Flow Conditions: 75 - 115 psia @ 40 psi/min

0 5 10 15 20 25 30 35 40

0

500

1000

1500

2000

2500

3000

3500

4000

Time (s)

FID

Res

po

nse

(p

A)

Diesel – High Speed GC Capillary: 20 m x 180 mm ID, DB-5 0.4 mm film Temperature Program: 75-325°C @ 250°C/min Flow Conditions: 75 - 115 psia @ 40 psi/min

0 10 20 30 40 50 60

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

Time (s)

FID

Res

po

nse

(p

A)

• 50 sq. micron

channels x 30 cm

• 30 sec CNT

growth time

• Integrated thin

film resistive

heating:

5 nm Ti

100 nm Pt

A.D. McBrady, B. Dick, V. R. Reid, A. Noy, R. E. Synovec and O. Bakajin, Anal. Chem., 2006, 78, 5639-5644.

Reid, V.R., Stadermann, M., Bakajin, O., Synovec, R.E. Talanta, 2009, 77, 1420-1425.

1 μm

SEM image Back of Chip

Hydrogen

Carrier

Gas

Commercial

GC Injector

Diaphragm

Valve Injection

Voltage/

Grounding

Leads

Variable

AC Power

Supply

(0 - 120 V)

V1 V2

Hydrogen

Carrier

Gas

Commercial

GC Injector

Diaphragm

Valve Injection

Voltage/

Grounding

Leads

Variable

AC Power

Supply

(0 - 120 V)

Vent FID

V

Deactivated

Silica Capillary

Leads

Hydrogen

Carrier

Gas

Commercial

GC Injector

Diaphragm

Valve Injection

Microfabricated SWCNT Column 30 cm, 50 μm x 50 μm

Voltage/

Grounding

Leads

Variable

AC Power

Supply

(0 - 120 V)

FID

V

Deactivated

Silica Capillary

Leads

FID

V

Top of Chip

Microfabricated GC-on-a-chip

with Carbon Nanotube (CNT) Stationary Phase and High-Speed Resistive Heating

collaboration with Lawrence Livermore National Lab (LLNL)

Alkane Mixture: hexane, octane, nonane, decane, undecane

LLNL CNT Chip: 30 cm x 50 mm x 50 mm; Carrier Gas: H2, 10 psi

Isothermal Separations and General Elution Problem

Time, seconds

FID

Sig

nal, v

olts

Time, seconds

FID

Sig

nal, v

olts

0 2 4 6 8 10 0

0.1

0.2

0.3

0.4

0 0.4 0.8 1.2 1.6 2

0

0.2

0.4

0.6

0.8

C11

C11

50 °C 100 °C

No single temperature provides best resolution per time !

C6

C6

Good resolution at front, but too resolved and diluted at end

Short time, but poor resolution at front

Solution to General Elution Problem: Rapid Temperature

Programming via Resistive Heating ~ 1500 °C/min

(Hexane, Octane, Nonane, Decane and Undecane)

Ti = 50 ºC, H2 carrier gas at 10 psi, 15 ms injection pulse

Application of 36 V yields 1560 ºC/min

0.6 0.8 1 1.2 1.4 1.6 1.8 2 2.2 2.4 0

0.2

0.4

0.6

0.8

1

1.2

Time, seconds

FID

Sig

nal, v

olts

50 °C 115 °C

C11

C6

C8 C9

C10

Conclusions

Optimizing 1D-GC peak capacity production

(1) novel injection techniques

(2) enhancements to temperature and pressure programming

technology

(3) fast, low dead volume detection design with high-speed

electronics

(4) implement modeling to direct experimental efforts

(5) explore new commercial instrumentation

Thank You !