Micromachined multi-analyte sensors: towards an ...weewave.mer.utexas.edu/MED_files/MED_research/MEMS_chem_snsr/nano...Current generation of electronic tongue chip 100 µm. D. Neikirk,

D. Neikirk, E. Anslyn, J. McDevitt, & J. ShearD. Neikirk, E. Anslyn, J. McDevitt, & J. Shear Micromachined sensor projectsMicromachined sensor projects

The University of Texas at AustinThe University of Texas at AustinNanoSpace 2000, Jan. 25, 2000

Youngsoo Sohn, John Levigne, Dr. Yi Deng, Adrian Goodey, Marc Rodriquez, Andrew Tsao, Theodore E. Curey

Dean P. Neikirk, Eric Anslyn, John McDevitt, and Jason ShearThe University of Texas at Austin

Department of Chemistry and BiochemistryDepartment of Electrical and Computer Engineering

Microelectronics Research Centerhttp://weewave.mer.utexas.edu/

This work was sponsored by the NIH, the Army Research Office (MURI), and the Beckman Foundation Technologies Initiative

Micromachined multi-analyte sensors: towards an “electronic tongue”



saltsweet

bitter

sour

sour

New sensing technology: What can we learn from nature??

– with “smart chemistry” we can make both general and selective receptors

• What might we sense?– foods, but also– things you don’t want to taste!

• blood, urine, biological and chemical warfare agents

• What about the sense of taste?– sense of taste is not based on

highly specific receptors, but instead on pattern recognition



R

RR

R

R

RR

R

H3C R

O

O

O

CH3CH3HO

OH

NHCO2

NH

O2CHO2C

_

+

_

+

COR

O

O

OHOH

NHCO2

_

+ COR

O OHO

OH

O

O R

R = Analyte

H+

H+

H+

H+

H+, Ca2+

H+, Ce3+

pH3 7 11

OCP

fluorescein

alizarin complexone

Indicator molecules interfaced to beads

• each receptor changes color in a distinct way when exposed to different environments

• “solid phase” support for receptor chemistry– PEG/polystyrene, agarose, glass “beads” all convenient supports– “micro-beads” support the chemistry



What happens when liquids flow across the beads?

• a BIG problem with PEG beads– dry state ~ 100 µm

diameter– “wet” state 200 µm

diameter– diameter a function

of chemical environment

pH ramp (up and down)



Bead sensors in micromachined storage wells

• use micromachining to form a microscopic “test-tube”– storage well for the bead “tastebuds”

• cover layer used to keep beads in place

photodetector (CCD)

illumination

fluid flowtransparent cover

sensor beadsupport substrate

storage well sensor bead

cover plates



Current generation of electronic tongue chip

100 µm



Pick-and-place loading of beads

• process and placement requirements similar to pcbassembly– rates of 10,000 parts placed per hour may be achieved using

moderately priced assembly systems

manual pick and place of a bead



Illumination Conditions ( 5-carboxy fluorescein Bead )Illumination Conditions ( 5-carboxy fluorescein Bead )

Reflected White Light:

Top Illumination

Transmitted White Light:

Bottom Illumination

EpiFluorescence: GFP Filter set



glass support substrate

beads (micro-spheres)

central ply

holes to allow fluid flow

top ply

Other methods of array fabrication• only common glass and polymer materials used

– holes could be made many ways• drilled, embossed • photolithographically using photo-imagable polymers

bottom ply



Initial demonstration of array using dry film resist

central ply built up from three 75

micron layers

top ply (one 37 micron layer)

glass support substrate

beadsholes to allow fluid flow

bottom ply

before lamination of cover layer

after lamination of cover layer


The University of Texas at AustinThe University of Texas at AustinNanoSpace 2000, Jan. 25, 2000Component integrationComponent integration



Array package and sample introduction

• sensor chip / fluid container / sampler as one unit– minimizes total volume of

bio-haz waste– “pre-filter” between pick-up

and sensor/sample chamber• removes particulates, whole

blood cells, etc.• can be impregnated with

analytes as necessary for assay

pick-up head

pre-filter

sensor array

sample chamber

D. Borichet al

vacuum canbreakable

barrier

– use vacuum “can” to pull sample into chamber

• precise sample volume• if beads stored in buffer,

simultaneously removes buffer

fluid flow



Fluid flow into a bead array

• forced (pumped) flow• note disappearance of air bubbles in storage wells

– flow through geometry essential for consistent bubble elimination



Fluid flow (pumped) into disposable plastic chip holder

• macroscopic view



2 3 4 5 6 7 8 9 10 11 12

example: pH

responses

Alizarin Complexone

OCP

Eosin B

Fluorescein

HNBA

HNPAA

Urine

Blood

Saliva



Movie Showing the Cycling of Four pH Indicators Between pH=2 and pH=12

Movie Showing the Cycling of Four pH Indicators Between pH=2 and pH=12

11

22

33

Trial #Trial #

blankblank

alizarinalizarin alizarinalizarin

HNBAHNBA HNPAAHNPAA



Bead 2,2 (ALZ Comp): Absorbance vs pHBead 2,2 (ALZ Comp): Absorbance vs pH

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8 10 12 14

pH

Abs

orba

nce



Flow rate: 1 mL/min; Image captures one point at every 30 sec.

(Deviation < 5%)

-0.1

0

0.1

0.2

0.3

0.4

0 10 20 30 40 50 60 70 80

BGR

Abs

orba

nce

Time (min)

10 mM DBU

10 mM acetic acid

#310(4-Hydroxy-3-nitrophenylacetic acid )

HNPAA



Passive fluid introduction

• Cross sectional view

bottom glass

micromachined Si

top glasshydrophobic

sample introduction port

hydrophilicchannel

dry film beads



Passive design

• Top and bottom view

Glass

Silicon

Micromachined Si

Dry Film

Si3N4

Inlet outlet



Function

sample introduction

bottom glass

dry film beads

micromachined Si

top glasschannel

hydrophilic

hydrophobic



Surface tension-driven fluid introduction


The University of Texas at AustinThe University of Texas at AustinNanoSpace 2000, Jan. 25, 2000Sample responses



Micromachines and chemistry: towards an “electronic tongue”

• wide range of potential applications– food, water monitoring– low cost, “real-time”

medical testing• initial demonstration of

– small ion detection– sugars, enzyme based

assays– antibody based assays– DNA recognition

reference

Ca 2+ Ce 3+

sugars

pH (2-5, 5-7, 9-12)

transparent top plate

bottom membrane

silicon substrate

micromachined well

sensing bead

100 µm

Documents

Micromachined multi-analyte sensors: towards an ...weewave.mer.utexas.edu/MED_files/MED_research/MEMS_chem_snsr/nano...Current generation of electronic tongue chip 100 µm. D. Neikirk,