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SPR (Surface Plasmon Resonance) Sensor Technologies Inventor: Professor Aaron Ho Pui HO, Department of Electronic Engineering

Summary
A new photonic biosensor design for detecting single test site devices based on measuring the molecular species relevant to medical and life shift of resonance angle. In the new design, the science disciplines has been developed. change of optical phase associated with the SPR Examples of such molecules are antibody, condition is measured. This has been proved to pathogens, viruses, cells and pollutants. The offer much better sensitivity. commercial potential of our invention is on low-Another important feature of the new phase-cost high throughput medical diagnostic devices. sensitive technique is the built-in capability to The physical phenomenon behind the invention is perform SPR measurement from a large area, called surface plasmon resonance (SPR), which which enables simultaneous data collection from can be viewed as a sheet of optically-induced multiple arrays of measurement sites. This may energy trapped near a metallic gold surface a lead to applications similar to that targeted by laser beam. Upon adhesion of target bio- florescent DNA chips. It is well known that the molecules to the gold surface, the resonance advantage of SPR is its non-involvement of any condition will change and therefore a positive florescent tagging process, which significantly identification is detected by noting a change in simplifies the preparation procedures of the optical energy reflected from the gold surface. biomolecule species. The only drawback to date At present a handful of SPR biosensors are is that detection sensitivity offered by the available commercially as analytical equipment florescent technique is still better in comparison for studying biochemistry reaction mechanisms. to that of SPR. In this respect, the improved They are sold at very high costs to biochemistry sensitivity and array measurement capability and medical laboratories. demonstrated from the new design will further improve the market potential of SPR biosensors. Conventional SPR biosensors in the market are Page 1 of 3 The Chinese University of Hong Kong Non-confidential Abstract of Technology Disclosure

Title: SPR (Surface Plasmon Resonance) Sensor Technologies

05/ENG/204 The present invention provides a new method of difference between the two signals will provide measuring optical phase information in surface the required phase measurement. The advantages plasmon resonance (SPR) sensors by using liquid of using LCM are low cost, small size, light crystal modulator. The operation of this SPR weight, low operation voltage, low power sensing system is based on two design principles, consumption and long life time. These active phase modulation and differential phase advantages allow us the freedom to design measurement technique. In the method of the compact systems for portable applications. The present invention, a liquid crystal modulator differential phase measurement technique also (LCM) is employed as a phase modulator for minimizes the system drift and thereby increases providing an active phase modulation, which system performance. means that we can continuously vary the Between the two signal traces, upon appropriate polarization retardation of the input optical beam signal recovery processing, will provide the according to our requirement. The retardation desired SPR phase. Since all signal traces are modulation in term provides two independent derived from the same optical beam our signals from the s- and p-polarized light. Since technique is a true differential phase system.SPR only affects the p-polarization, the phase -------------------------------------------------------------- Question &Answer

Question 1: On what specific applications has this technique been tested, and what equipment is required for the phase sensitive measurements?

This technique has been used for measuring the salt concentration in water (for demonstrating an ultimate sensitivity limit in ~10-8 regime), real-time monitoring of binding of (i) BSA antibody, (ii) H3 influenza antibody. The equipment required for building the system: personal computer with data logging head, data analysis software developed in-house, HeNe laser, liquid crystal phase modulator (may be constructed from components used in low-cost liquid crystal displays), photodetectors, piezoelectric transducer, polarizing beam splitters, common optical and electronic components.

Question 2: What limitations are there with the phase sensitive technique over the resonance angle technique?

The phase sensitive technique has smaller measurement dynamic range in comparison to the one that measures the resonance angle. We are currently solving this drawback by developing several techniques including optimization of sensor layer stack, use of multi-pass interferometry, and incorporation of wide angle illumination. Page 2 of 3 The Chinese University of Hong Kong Non-confidential Abstract of Technology Disclosure

Title: SPR (Surface Plasmon Resonance) Sensor Technologies

Question 3: How about improved sensitivity – can this be quantified and thereby translated into an increase in throughput rate for scanning systems?

-8Until now the best sensitivity we have achieved in our laboratory is 1.9  10 refractive index unit (RIU). This is approximately 10 times better than that reported from Texas Instruments’ angular SPR module, SPREETA. [Ref: T. M. Chinowsky et al, Performance of the Spreeta 2000 integrated surface plasmon resonance affinity sensor, Sensors and Actuators B: Chemical, 91(2003), 266-274.]. Our experimental sensitivity limit of BSA antibody detection is ~0.1 ng/ml. The main advantage of using the phase-sensitive SPR technique lies in the possibility of performing parallel detection on 2-dimensional arrays by simply capturing the interference image of the sensor surface in real-time. The angular technique requires linear detector arrays to locate the resonance angle, thereby making it much more difficult to implement SPR imaging of the sensor surface.

Question 4: Is this a technology that would form part of a High Throughput Screening equipment, and therefore best developed in collaboration with, or licensed to industry partner?

Because of the above reason, we anticipate that our phase-sensitive measurement approach will be readily developed into a real-time label-free bio-chip platform similar to the florescence-based DNA-chip available in the market. In fact, at present we have already developed a SPR phase imaging system in our laboratory for monitoring specific binding at sensor sites functionalized with BSA and H3 influenza antibodies.

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Supplementary Information
Inventor: Ho, Ho Pui | Wong, Chi Lok | Wu, Shu Yuen | Law, Wing Cheung | Lin, Chinlon | Kong, Siu Kai
Priority Number: US7365855B2
IPC Current: G01B000902
US Class: 356450
Assignee Applicant: The Chinese University of Hong Kong
Title: Optical sensing devices with SPR sensors based on differential phase interrogation and measuring method using the same
Usefulness: Optical sensing devices with SPR sensors based on differential phase interrogation and measuring method using the same
Summary: For detecting biological, biochemical or chemical characteristic of species (claimed).
Novelty: Optical sensing device for detecting biological or chemical species, comprises beam splitter to divide light into two beams, and surface plasmon resonance unit having sensing surface for reflecting beam from splitter at least twice
Industry
Electronics
Sub Category
Circuit Design
Application No.
05/ENG/189 - Optical Surface Plasmon Resonance Sensor Based on Differential Phase Interrogation and Phase Enhancement using a Fabry-Perot Cavity 05/ENG/204 - A Simple Differential Phase Imaging Surface Plasmon Resonance Sensor using Liquid Crystal Modulator Patent Status: Two US Patents Pending ----------------------------------------------- 05/ENG/189
Country/Region
Hong Kong

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