Nanomaterial’s Application in Biotechnology

Lei SunProject manager

Digital Health GroupIntel Corp.

Outline• Overview of nanomaterial’s application in

biotech, especially in cancer diagnosis and treatment.

• Application Example I: Gold Nanoparticle’s application in DNA detection.

• Application example II: Quantum dot’s application in cell labeling.

Drug DiscoveryPatient Care

Biomarkers

What Are Biomarkers? Concentration/

abundanceGlucoseelectrolyteCholesterol

…

Insulin

PSA (prostate specific antigen)

HER-2 (Breast cancer biomarker)

CA-125 (Ovarian cancer biomarker)

…

???

mg/mL

ng/mL

pg/mL

At this stage, cancel cells have to detected

through ultra-sensitive biomarkers

Gold Nanoparticle and Its Application in Ultra-sensitive DNA and Protein Detection

TEM image of the cluster of

DNA-functionalized gold nanoparticles

Assembly of DNA-functionalized Gold Nanoparticles                                       

Use functionalized Gold Nanoparticles to Detect DNA                                        

Color change of the gold colloidal solution reflect change of the cluster size

Au…ATTCCGA TTAGGCT…Au …TAAGGCT…AATCCGA…

DNA probe Sequences are designed so that the target DNA will link the particles together

Ultra-sensitive Detection of DNA with Nanoparticle assembly Array

electrodes targetDNA

Silver Staining

The gold nanoparticles are linked together by

target DNA

Measure the resistance between 2 electrodes to tell the concentration of target DNASensitivity 500 fmol or 109 molecules.

Application of Ultra-sensitive DNA Detection

Virus detection – HIV, SARS, Bird flu, etc.

Biomarker detection – DNA/RNA related to cancer and drug metabolism.

Personalized Medicine – Predict each patient’s response to certain treatment based on his/her gene.

Quantum Dot and Its Application in Cell labeling

What are Quantum Dots What are Quantum Dots (QDot)?(QDot)?

655 605 585 565

525 nmSize of the nanocrystal determines the color

Size is tunable from ~5-15 nm (±3%) Size distribution determines the

spectral width

Highly fluorescent, nanometer-size, single crystals of semiconductor materials

Size of Cells & QdotsSize of Cells & QdotsSize of Cells & QdotsSize of Cells & Qdots

                                                                                                              

    

Qdot Conjugates are Qdot Conjugates are Engineered Engineered

Core Nanocrystal (CdSe)- Determines color

Inorganic Shell (ZnS)– Improves brightness and stability

Organic Coating - Provides water solubility

and functional groups for conjugation.

Biomolecules-Covalently attached to polymer shell

- Immuoglobulins (Abs)- Streptavidin, Protein A- Receptor ligands- Oligonucleotides

15 - 18 nm

•High level Her 2/neu expression in SK-BR-3 cells

•Quantum dots is up to 50x brighter.

•Low level of Her 2/neu expression in MDA-MB-231 cells

•Organic dye is undetectable.

Excellent Brightness and Photo-Excellent Brightness and Photo-stability stability

Sharp and distinguishable Sharp and distinguishable peaks enable multi-color peaks enable multi-color

detectiondetection

Minimal (<5%) cross-talk using 20nm bandpass

filters

Example Application - Example Application - Qtracker® Cell Labeling KitsQtracker® Cell Labeling Kits

Goal of Qtracker:

To provide customers an approach to track live cells using Qdot-sav.

cell

+

Qdot

Why do we want to Tracking living cells?

• To understand cell differentiation

• To study cell-cell interaction

• To monitor cancer cells’ response to drug/ radiation treatment.

Qdot Delivered into Live CellsQdot Delivered into Live Cells

No Biotin 10x Biotin 50X Biotin

As the concentration of quantum dots increases, the signal strength from the

cell increases

Cellular Retention Time of Cellular Retention Time of QDotsQDots

The cells are still alive after multiple days. When the cells divide, the dots in the cell are divided also, causing signal to drop according to division rate.

Three-Color QDots Cell Three-Color QDots Cell LabelingLabeling

Different Qdots can be functionalized so that each dot can enter a specific type of cells. Enables multi-color labeling and tracking. Cell-cell interaction can be studied with the same approach.

““Scratch Assay” with QDots Scratch Assay” with QDots Cell Labeling KitCell Labeling Kit

Cell’s migration speed can be measured by scratch an “X” mark in a cell culture, then monitor the time it takes for the cells to cross the boundary.

Other Qdot ApplicationsOther Qdot Applications• Proteomics – Protein detection• Research Cell Biology – cell

tracking• Pathology – tissue analysis• Pharmaceutical R&D Products

– High Content Screening – Mid Content Screening – Cell

based assays– Multiplex Cellular Assays

• In vivo Imaging Agents