Microsystem for analyzing blood

• US 8,648,396 B2
• Filed: 12/30/2010
• Issued: 02/11/2014
• Est. Priority Date: 10/18/2010
• Status: Expired due to Fees

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: Huang, I-Yu, Hsieh, Chia-Hsu
• Primary Examiner(s): Sandvik, Benjamin
• Assistant Examiner(s): Cruz, Leslie Pilar
• Application Number:
  US12/982,556
• Publication Number:
  US 20120091512A1
• Time in Patent Office: 1,139 Days
• Field of Search: None
• US Class Current: 257/253
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4148 Integrated circuits therefor, e.g. fabricated by CMOS processing CMOS processing per se H01L21/82
• CPC Class Codes: G01N 33/492 Determining multiple analytes

Abstract

The present disclosure utilizes the MEMS (Micro Electro Mechanical Systems) process and packaging method to produce a microsystem for analyzing blood which is capable of detecting several kinds of ions. The microsystem for analyzing blood has a miniaturized reference electrode, so size of the microsystem can be greatly reduced. The microsystem further has a gate detecting area larger than a conventional planar ISE or a conventional ISFET does, so interference with signals can be avoided, and packaging difficulty and blood leakage can be reduced. Therefore, the microsystem is thin and small, reacts rapidly, and has a high accuracy, and a high compatibility with IC (integrated circuit) process. In addition, the microsystem has high stability of long-term potential, low offset-potential characteristics, low alternating current impedance, high stability of dynamic reference potential, low electrochemical noises and high reproducibility of the electrode.

Claims

1. A microsystem for analyzing blood, comprising:

an integrated structure, having a micro reference electrode, a plurality of extended gate field effect transistor (EGFET) elements and a circuit, wherein each extended gate field effect transistor (EGFET) element has a source extension, a drain extension and a gate extension, the gate extensions are disposed at the periphery of the micro reference electrode and essentially separated from the micro reference electrode by a same distance, and the circuit electrically connects the source extensions or the drain extensions;

a plurality of ion detecting membranes, disposed on a surface of the gate extensions;

a packaging structure, assembled with the integrated structure, wherein the packaging structure has a plurality of first through holes, a plurality of second through holes, a third through hole, a fourth through hole and a fifth through hole, the first through holes corresponding to the ion detecting membranes, the second through holes corresponding to the source extensions or the drain extensions which are not electrically connected by the circuit, the third through hole corresponding to an extension of the source extensions or the drain extensions which is electrically connected by the circuit, and the fourth through hole and the fifth through hole being disposed at a corresponding position above the micro reference electrode; and

a conductive material, disposed in the fourth through hole and contacting the micro reference electrode;

wherein the micro reference electrode has a reference electrode body and an electrically connecting junction, the electrically connecting junction is formed on the reference electrode body, and the electrically connecting junction corresponds to the fifth through hole.

2. The microsystem for analyzing blood as claimed in claim 1, wherein the reference electrode body comprises a Ti (titanium) layer, a Pd (palladium) layer, a Ag (silver) layer and a AgCl (silver chloride) layer in this order, and the AgCl (silver chloride) layer contacts the electrically connecting junction.

3. The microsystem for analyzing blood as claimed in claim 1, wherein the conductive material is a KCl (potassium chloride) gel.

4. The microsystem for analyzing blood as claimed in claim 1, wherein the fourth through hole has a first cavity and a second cavity, the second cavity facing the micro reference electrode, and the first cavity and the second cavity tapering inward from two side surfaces of the packaging structure respectively and communicating with each other.

5. The microsystem for analyzing blood as claimed in claim 4, wherein the conductive material is disposed in the second cavity, and the first cavity exposes part of the conductive material.

6. The microsystem for analyzing blood as claimed in claim 1, further comprising a wire electrically connected to the micro reference electrode.

7. The microsystem for analyzing blood as claimed in claim 6, further comprising a molding compound disposed in the fifth through hole, and the molding compound encapsulates and fixes the wire.

8. The microsystem for analyzing blood as claimed in claim 1, wherein the ion detecting membrane is an ion selective membrane (ISM).

9. The microsystem for analyzing blood as claimed in claim 8, wherein the ion selective membrane (ISM) is a H⁺ selective membrane, a Ca²⁺ selective membrane, a K⁺ selective membrane, a Na⁺ selective membrane or a NH₄⁺ selective membrane.

10. The microsystem for analyzing blood as claimed in claim 9, wherein the H⁺ selective membrane is a Ta₂O₅ (tantalum oxide) membrane, and the ingredients of the Ca²⁺ selective membrane, the K⁺ selective membrane, the Na⁺ selective membrane or the NH₄⁺ selective membrane comprise an ionophore, a plasticizer, an ionic additive, a polymer and an organic solvent.

11. The microsystem for analyzing blood as claimed in claim 10, wherein the ionophore of the Ca²⁺ selective membrane is ETH129, the plasticizer is NPOE, the ionic additive is K-TpClPB, the polymer is PVC (polyvinyl chloride), and the organic solvent is THF (tetrahydrofuran);

the ionophore of the K⁺ selective membrane is is valinomycin, the plasticizer is DOS, the ionic additive is K-TpClPB, the polymer is PVC (polyvinyl chloride), and the organic solvent is THF (tetrahydrofuran);

the ionophore of the Na⁺ selective membrane is Sodium ionophore X, the plasticizer is NPOE, the ionic additive is K-TpClPB, the polymer is PVC (polyvinyl chloride), and the organic solvent is THF (tetrahydrofuran);

the ionophore of the NH₄⁺ selective membrane is TD19C6, the plasticizer is BBPA, the ionic additive is KTCPB, the polymer is PVC (polyvinyl chloride), and the organic solvent is THF (tetrahydrofuran).

12. The microsystem for analyzing blood as claimed in claim 11, wherein the ionophore ETH129 of the Ca²⁺ selective membrane is 1.0 wt %, the plasticizer NPOE is 65.6 wt %, the ionic additive K-TpClPB is 0.6 wt %, the polymer PVC (polyvinyl chloride) is 32.8 wt %, and the content of the organic solvent THF (tetrahydrofuran) is 1.3 mL;

the ionophore valinomycin of the K⁺ selective membrane is 1.1 wt %, the plasticizer DOS is 67.6 wt %, the ionic additive K-TpClPB is 0.6 wt %, the polymer PVC (polyvinyl chloride) is 30.7 wt %, and the content of the organic solvent THF (tetrahydrofuran) is 1.2 mL;

the ionophore Sodium ionophore X of the Na⁺ selective membrane is 0.7 wt %, the plasticizer NPOE is 66.1 wt %, the ionic additive K-TpClPB is 0.2 wt %, the polymer PVC (polyvinyl chloride) is 33.0 wt %, and the content of the organic solvent THF (tetrahydrofuran) is 1.9 mL;

the ionophore TD19C6 of the NH₄⁺ selective membrane is 3.0 wt %, the plasticizer BBPA is 67.0 wt %, the content of the ionic additive KTCPB is 0.5 mg, the polymer PVC (polyvinyl chloride) is 30.0 wt %, and the content of the organic solvent THF (tetrahydrofuran) is 0.5 mL.