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IFT Summit Conference : Food Packaging Innovations - May 7-9, Baltimore, Maryland

Nano Bio Sensors and Integrated Microsystems for Intelligent Food Packaging

Dr Janagama, D Goud, Research StaffDr PM Raj, Assistant DirectorDr Mahadevan K Iyer, Research Director Dr Rao R Tummala, Director & Professor, MSE & ECE

Microsystems Packaging Research CenterGeorgia Institute of TechnologyAtlanta, Georgia


OUTLINE

• Packaging for Convergent Micro Systems

• Bioelectronics & Bio sensors

• Nano Bio sensors & few case studies relevant to Food Packaging

• Integration of Nano Bio Sensors with Electronics& RF Components – Intelligent Food Packaging

• Summary


GaTech – Packaging Research Center (PRC)

““Package is the System” Package is the System” –– System On System On Package Package ((SoPSoP))

System:System: Convergence of Computing, Convergence of Computing, Communication, Consumer & BiomedicalCommunication, Consumer & Biomedical

System on Package

System on Package


PRC Vision of Digital Convergence by 1000XPRC Vision of Digital Convergence by 1000X

Digital + Analog + RF + Optical+ Sensors•Computing/Internet, Digital Audio

•Digital Imaging/Video

•Cellular/Wireless, GPS/Satellite

•Sensors

•And, of course, timekeeping!


Trend to Digital ConvergenceTrend to Digital Convergence

1970 1980 1990 2000

100

1000

10000

100000

Vol

ume(

cm3 )

W/S

SMART“Watch” & Bio-sensor

SINGLE FUNCTION

MULTI -FUNCTION

MEGA-FUNCTION

Notebook

PC

LaptopCellular

Func

tiona

l Den

sity

or

Com

pone

nt D

ensi

ty /

cm3 )

TODAY

CURRENTFOCUS

NANO PILLCAMERA

PERSONAL NETWORKCOMMUNICATOR

MOLECULARMOLECULARMANIPULATIONMANIPULATION

MULTIFUNCTIONCELL PHONE

NANO-BIO-INFO SYSTEMSNANONANO--BIOBIO--INFO SYSTEMSINFO SYSTEMS

FUTUREFOCUS

SIPSIP

SIP

NanoWLP

NanoWLP

Multi-to Mega functionPkg. by SOP

Multi-to Mega functionPkg. by SOP

SOP

NanoSystems

NanoSystems

SOC

NanoDevices

SOC


Vision of System on PackageVision of System on Packageat Georgia Tech Packaging Research Centerat Georgia Tech Packaging Research Center

Mega-FunctionSystems

Mega-FunctionSystems

MechanicalMechanical

ElectronicElectronic••DigitalDigital

••RFRF••OptoOpto

ChemicalChemical

ThermalThermal

BiologicalBiological


Bio Micro/Nano System Integration

BIOELECTRONICSBIOELECTRONICSSystem on PackageSystem on Package

BIOLOGYBIOLOGY

CHEMISTRYCHEMISTRY

ELECTRONICSELECTRONICSMSE, ECE, ME, MSE, ECE, ME, ChEChE


BioBio--electronic Technologies & Applicationselectronic Technologies & Applications

BiosensorsBiosensorsBio Implants for Bio Implants for

Health monitor & cureHealth monitor & cure

Bio computing Bio computing with DNAwith DNA

Bio actuatorsBio actuators

Electronic NoseElectronic Nose

Electronic PillsElectronic Pills

GeneticGeneticToggle SwitchesToggle Switches

Electronic EyeElectronic Eye(Artificial CMOS retina)(Artificial CMOS retina) BIOELECTRONICSBIOELECTRONICS

Classification of Bio Sensors

--++

BIOSENSORS

DNA Biosensors RNA Biosensors

Physiological BiosensorsFood & Pharmacological

Biosensors

Receptor Biosensors

Protein Biosensors

Cell BasedBiosensors

Peptide Biosensors

Protein, DNA/RNA and enzyme based sensor systems .1. Food Safety and Security• Detection of risks involved in Genetically Modified (GM) foods• Biosensors for real-time analysis of food products for early detection of spoilage microflora.• Rapid on-line identification of contaminants in freshly collected and processed milk.• Botulinum, E. coli and other bacterial and fungal contaminants.• Detection of the ricin, the deadly toxin from castor bean.

2. Clinical Diagnostics (early detection of cancer diseases):• Prostate –Specific Antigen (PSA) for early detection of prostate cancer.• HER2 (or HER2/neu), BRCA1 and BRCA2 I genes, cardiovascular, and other diseases

3. Industrial Bioprocess Control and Monitoring• Enzyme sensor for detection of hydrolysis of starch into glucose useful for the food and

pharmaceutical industries.• Enzyme sensor for detection of hydrolysis of starch into cyclodextrins useful compound for the

food, cosmetic, pharmaceutical, and plastic industries.• Monitoring protein products generated by recombinant DNA technology during microbial cell or mammalian

cell fermentation.

4. Environmental Safety• Analysis of explosive trinitrotoluene (TNT) in the soil and ground water • Salmonella and Anthrax pathogens• Chemical toxins Detection of industrial toxic effluents, and human and animal waste into water

bodies is an important aspect of environmental safety and protection.

5. Drug discovery and AbuseCocaine sensor for rapid detection and quantification of coca alkaloids

APPLICATION OF BIOSENSORS

Working Principle of a Biosensor

Basic Building blocks of a Basic Building blocks of a BioSensorBioSensor

Schematics of a typical biosensor: (a) bioreceptors: SSchematics of a typical biosensor: (a) bioreceptors: S-- substrate, Psubstrate, P--products, proteins, nucleic acids (b) transducer, (c) signal ampproducts, proteins, nucleic acids (b) transducer, (c) signal amplifier, (d) lifier, (d) signal processor, and (e) signal display. signal processor, and (e) signal display.

Bio recognition and signal transduction methods

BIOMECHANISMSBIOMECHANISMSThe important biological component of a biosensor is a receptor called bioreceptor, which recognizes the analyte or target molecules. These biorecognition elements are specific and exclusively sensitive to a particular substance.

The main groups of biological elements are:• Proteins (antigens and Anti-bodies) • Nucleic acids (DNA/RNA)• Natural and synthetic receptors• Enzymes (biocatalysts)

DNA and RNA hybridization DNA and RNA hybridization mechanisms

Biosensing mechanism of antigen and anti-body binding and Immune complex Immune complex formation

mechanisms

formation

• No involvement of exogenous molecules or labels such as conjugation with enzyme, radioactive fluorescence, or chemiluminescence molecules.

•The probe and target binding events or enzyme and substrate reactions are recorded by the transducer in the absence of any label requirement.

• A polymerase chain reaction (PCR) free detection systems for DNA identification.

• It is a nano-scale detection of the target molecules, a key factor in early detection of diseases such as breast cancer and AIDS

• Rapid and high-throughput detection

• Detection processes are simple, user friendly, fast, and cost effective.

• Reduced power requirement, and easier recycling

• Repetitive, portability, and stability

• Use of analytical methods such as high performance liquid chromatography (HPLC), near-infrared spectroscopy or specific enzymatic methods for characterizing food. These processes are time consuming.

NANOBIOSENSORS CONVENTIONAL DETECTION METHODS

• Appropriate sensing technologies to detect substances in parts per trillion for food safety, quality and process control.

• Development of new sensing devices taking the advantage of miniaturization of electronics and nanobio materials.

. • On site analysis for safety and quality in a processing or packaging plant.

Intelligent Food Packaging– Micro/ Nano sensors for Quality and Process Control

• Detection of toxins, pathogens and chemicals in foodstuffs on the spot.

• Integration of Sensing elements with electronics and RFIDs in ultra thin , ultra miniaturized embedded modules

Specific Needs for Bio Sensors in Food and Drink Industries• To determine specific components in the food and drinks such as

sugars, proteins, vitamins and fats.

• To detect and quantify chemical contaminants such as pesticides, heavy metals, and antibiotics.

• To detect pathogenic bacteria (e.g. E. coli 0157, Listeria,Salmonella, Campylobacter, Vibrio) and viruses (e.g. Small Round Structured Viruses).

• To detect food borne toxins (e.g. Staphylococcus Enterotoxins, Botulinum neurotoxins, Mycotoxins and Paralytic/Diarrhetic shellfish toxins). These biomolecules are considered powerful weapons and"road map for terrorists" to destroy humans and livestock indiscriminately.

• Monitoring the freshness of aquatic foods including fish, and fermentation processes.

Recent accomplishments at GaTech – Microsystems Packaging Research Center

Si Microresonators based protein biosensor

Si Microresonator Biofunctionalized with protein (confocal image) AFM image

• Demonstrated the proof of concept using length-extensional resonators as mass sensors

• Further implementation- Piezoelectric transducers- Performance characterization and electrical measurements- Extend Si microresonators for fabrication of DNA and enzyme

based biosensors.

Frequency

Amplitu

de

Dw

AdvantagesHigher sensitivityHigh-Q in air Simple fabricationOn-chip transductionPortable detections

Sensor Arrays

ZnO NANOBELTS/WIRE BASED BIOSENSOR FOR ELECTRICAL DETECTION OF PROTEIN

ZnO nano belts were cleaned and treated with 3—(trimethoxysilyl) propyl aldehyde, and then biofunctionalized

Coating the nanobelts with silicon nitride for protection of ZnO

Surface treatment of the nano- structures

ZnO nanobelts biofunctionalized with protein

Hybridization with fluorophore -labeled antibodies

Detection with confocal microscopy Electrical measurements measurementand surface characterization

I-V Characteristics

-1.50E-05

-1.00E-05

-5.00E-06

0.00E+00

5.00E-06

1.00E-05

1.50E-05

-1.5 -1 -0.5 0 0.5 1 1.5

Voltage

Cur

rent Before Func

First after FuncSecond after Func

Electrical impedance measurements

• Demonstrated electronic detection of protein

• Further implementation- Sensitivity- Repeatability- Extend ZnO belts for fabrication of DNA and enzyme-catalyst based biosensors

Electrode

ZnO nanowire


Dielectrophoresis-on-a-chip

The dielectrophoresis-on-a-chip is used to process and assess microorganisms and cells, protein, DNA, and RNA from nano-quantity of the samples by sorting, trapping and separating them precisely and rapidly

MULTI-WALLED CARBON NANOTUBES (MWCNTs) BASED BIOSENSOR FOR ELECTRICAL DETECTION OF PROTEINCarbon nanotubes were attached on glassy graphite electrode using N,N, dimethlyformaide (DMF), and then biofunctionalized.

Carbon nanotubes

O.D. × wall thickness × length 20-50 nm × 1-2 nm × 0.5-2 µm Carbon nanotubes attached on glassy graphite electrode

Surface treatment of the nano-structures

Biofunctionalization with generic anti- S-100 antibodies of Schwann nerve cells

Hybridization with S-100 antigen, and detected with FITC labeled IgG.with confocal microscopy

1000 1500 2000 2500 3000 3500

-0.02

0

0.02

0.04

0.06

0.08

WAVE NUMBER 1/cm

INTE

NS

ITY

AS RECEIVED

C=O AFTER TREATMENT

1000 1500 2000 2500 3000 3500

-0.02

0

0.02

0.04

0.06

0.08

WAVE NUMBER 1/cm

INTE

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ITY

AS RECEIVED

C=O AFTER TREATMENT

Carboxylation of carbon nanotubes conformed by FTIR spectra

• Demonstrated surface modification and biofunctionalization of carbon nanotubes using protein.

• Further implementation- Electrical measurements by differential pulse voltammetry (DPV).

- Electrochemical biosensors for protein , DNA and enzyme- catalyst reactions

SEM of MWNTs Confocal image of biofucntionalized MWNTs


• Enzymatic hydrolysis of starch into glucose.• Enzymatic hydrolysis of starch into cyclodextrins

Nanobio sensors for detection of enzyme based hydrolysis in food and pharmaceuticalindustries

• Multi-enzymatic sensors for sucrose determination

• Glutamate Sensors for measuring glutamate concentration in theproduction of mono-sodium-glutamate (MSG).

• Amperometric mediated carbon nanotube paste biosensor forfructose determination.

• Ethanol Sensors- microbial sensors for measuring ethanol concentration in alcoholic fermentation.

• Determination of malic acid in real samples by using enzymeimmobilized reactors amperometric detection.

ZnO NANOBELTS/WIRE BASED BIOSENSOR FABRICATED FOR ELECTRICAL DETECTION OF STARCH HYDROLYSIS

ZnO nano belts were cleaned and treated with 3—(trimethoxysilyl) propyl aldehyde, and then biofunctionalized

Coating the nanobelts with silicon nitride

Surface treatment of the nano- structures

ZnO nanobelts coated with starch solution.

Hydrolyzed with amylglucosidase enzyme.

Surface characterizationElectrical

measurements

SEM images: (a) ZnO nanowire with Au electrodes; (b) control sample before hydrolysis (bulk of seen onthe wire); (c) control sample after incubating with buffer (bulk of starch still sitting on ZnO nanodevice; (d) test sample before hydrolysis (bulk of starch seen on ZnO nanodevice, (e) test sample shows degradation of starch after enzymatic hydrolysis .

• Demonstrated electronic detection of enzymatic hydrolysis of starch

• Further implementation -Sensitivity-Repeatability

-1.50E-05

-1.00E-05

-5.00E-06

0.00E+00

5.00E-06

1.00E-05

1.50E-05

-1 -0.5 0 0.5 1

Voltage(V)

Cur

rent

(A)

Before Func

After loading

After Hydrolysis

Electrical Impedance measurements

ZnO nanobelt/wire with out starch applied

1.07E-5S

After loading starch

1.08E-5S

After hydrolysis of starch

1.07E-5S

Electrical Conductance Dat


Intelligent Food Packaging: Integration of nanobiosensors with fluidic channels, detectors, electronic and wireless (RFID) components

Ultra thin micro miniaturized module

Radio Frequency IDentification is detection of tagged objects from a remote transponder (tag) including an antenna and a microchip transceiver (IC) using a local querying system (reader or interrogator)

IC Antenna

GaTech – PRC research in integration of micro and nano components in ultra thin polymer substrates

RFID technology offers the intelligence to food packaging. RFID serves as a mobile database holding valuable information, such as the product's history, location and destination.


Liquid Crystal Polymers as Packaging SubstratesAdvantages

–– Excellent high frequency performanceExcellent high frequency performance

•• low dielectric constant of 2.9low dielectric constant of 2.9

•• low loss tangent of 0.002low loss tangent of 0.002–– Controlled low coefficient of thermal expansionControlled low coefficient of thermal expansion

(0 to 30 ppm/°C)(0 to 30 ppm/°C)•• PWB substrate target is 5 to 8 ppm/CPWB substrate target is 5 to 8 ppm/C

–– Excellent barrier properties (similar to glass) Excellent barrier properties (similar to glass) •• very low moisture absorption (<0.04 percent)very low moisture absorption (<0.04 percent)

–– Low costLow cost


Advantages of Liquid Crystal Polymers (contd.)

–– High strengthHigh strength•• tensile strength of 30 tensile strength of 30 KpsiKpsi•• tensile modulus of 1.3 tensile modulus of 1.3 MpsiMpsi

–– Good adhesion to metalsGood adhesion to metals

•• copper peel strength = 12 copper peel strength = 12 psipsi•• High LCP melt temperaturesHigh LCP melt temperatures

277 to 340 C277 to 340 C–– SelfSelf--reinforcing uniform dielectricreinforcing uniform dielectric

•• can be fabricated in any thickness multiple of 2 milscan be fabricated in any thickness multiple of 2 mils•• no effects or defects from resin/glass intersectionsno effects or defects from resin/glass intersections

Intelligent Food Packaging – Building Blocks

Core

Digital ICR

RFID Antenna

RF IC

C

<100µm

20~100µm 1~50 µm

50~200 µm

Nano bio sensors

< 0.5 mm

RF 200 µm

Embedding electronic components in ultra thin polymer substrate materials integrated with nano bio sensors and RFID components - GaTech Packaging Research Center

RFID Antennas fabricated in Liquid Crystal Polymer ( LCP) (Ref: M.tentziri, Ga Tech)

LCPs are Bio Compatible materials


SUMMARY

Nano Bio sensing components offer tremendous applications to Food- packaging , quality Control and safety .

Intelligent Food Packaging : Integration of sensing, data storage and communication components with Food packages will be one of the future thrust research areas .


THANK YOU

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