High throughput chemical analysis by improved desorption/ionization on silicon mass spectrometry

• US 20030057106A1
• Filed: 09/12/2002
• Published: 03/27/2003
• Est. Priority Date: 09/12/2001
• Status: Abandoned Application

• Current Assignee: Mass Consortium Corporation
• Original Assignee: Mass Consortium Corporation
• Inventors: Shen, Zhouxin, Siuzdak, Gary
• Application Number:
  US10/242,018
• Publication Number:
  US 20030057106A1
• Time in Patent Office: Days
• US Class Current: 205/655
• CPC Class Codes: C25F 3/12 of semiconducting materials
• CPC Class Codes: G01N 1/22 in the gaseous state specially adapted for biological material G01N33/497; measuring breath flow A61B5/087
• CPC Class Codes: H01J 49/0418 for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A method of making improved substrates for desorbing and ionizing analytes takes an n-type semiconductor substrate and provides a strong light source. By focusing the illumination from the light source onto the n-type semiconductor substrate results in at least one lit region on the n-type semiconductor substrate. The substrate is electrochemically etched with a low current during illumination to form at least one sample reservoir, each sample reservoir being formed at a respective lit region on the n-type semiconductor substrate.

Claims

1. A method of making improved substrates for desorbing and ionizing analytes comprising:

providing an n-type semiconductor substrate;

providing a light source;

focusing the illumination from the light source onto the n-type semiconductor substrate to result in at least one lit region on the n-type semiconductor substrate; and

electrochemically etching the n-type semiconductor substrate with a low current during illumination to form at least one sample reservoir on the substrate, each sample reservoir being formed at a respective lit region on the n-type semiconductor substrate.

2. The method of claim 1, wherein the substrate is silicon.

3. The method of claim 1, wherein the light source is a fiber optic light source and a pair of achromatic lenses are used to focus the illumination on the substrate.

4. The method of claim 1, wherein the electrochemical etching is performed at a constant low current of about 4 mA.

5. The method of claim 1, further comprising:

oxidizing at least one sample reservoir to form an oxidized sample reservoir;

etching the oxidized sample reservoir to form a double etched sample reservoir.

6. The method of claim 5, wherein the oxidizing step is performed with O₃, and the etching of the oxidized sample reservoir is performed with a solution containing HF.

7. The method of claim 1 wherein the etching is performed for about 1-2 minutes while illuminating the substrate with a light intensity of about 20-50 watts per square centimeter.

8. A method of making improved substrates for desorbing and ionizing analytes comprising:

providing an n-type silicon substrate;

providing a white light source;

masking the illumination from the strong light source to define a light pattern;

focusing the light pattern on the n-type semiconductor substrate to result in a plurality of lit regions on the n-type semiconductor substrate lit with a strength of about 20-50 milliwatts per centimeter squared;

electrochemically etching the n-type semiconductor substrate for 1-2 minutes at a current of about 4 milliamps during illumination to form a sample reservoir at each lit region;

oxidizing at least one sample reservoir to form an oxidized sample reservoir; and

chemically etching the oxidized sample reservoir to form a double etched sample reservoir.

9. A method of simultaneously assaying a plurality of organic compound analytes for a desired physical property comprising:

providing a n-type semiconductor substrate having at least one double etched sample reservoir defined therein;

providing a sample having at least one organic compound analyte;

providing a source of radiation

introducing less than one picomole of the sample containing to the double etched sample reservoir to adsorb the sample to the substrate free of matrix material;

irradiating the sample reservoir so that the sample reservoir absorbs the radiation and desorbs the analyte;

analyzing the desired physical property of the desorbed and ionized analyte.

10. The method of claim 9, wherein the sample is introduced by being deposited in a solution and dried.

11. The method of claim 9, wherein the substrate is a low resistivity silicon substrate.

12. The method of claim 9, wherein the number of low mass background ions generated by the substrate when irradiated is substantially less than the number of ions generated by the sample.

13. The method of claim 9, wherein the desired physical property is mass, and the analysis of the desorbed and ionized analyte comprises measuring the mass to charge ratio of the analyte.

14. The method of claim 9, wherein the substrate has a plurality of sample reservoirs, and a plurality of samples are provided with each sample being introduced to a respective sample reservoir, and wherein further the plurality of sample reservoirs are irradiated, and the analytes desorbed and ionized from each sample reservoir are separately analyzed for the desired physical property.

15. The method of claim 14, wherein the desired physical property is mass, and the analyzing the desorbed and ionized analyte comprises measuring the mass to charge ratio of the analytes, wherein each sample is illuminated and analyzed in a period of less than about 5 seconds.

16. The method of claim 9, wherein the sample comprises a protein or enzyme.

17. The method of claim 15, wherein the protein or enzyme has a molecular weight of greater than about 5,000 Daltons.

18. The method of claim 9, wherein at least one analyte comprises a conventional tag, wherein the analysis of the analyte measures the conventional tag along with the analyte as a whole, and does not measure the conventional. tag separately.

19. The method of claim 9, wherein the sample comprises a plurality of analytes, and the analytes are substantially simultaneously desorbed and ionized upon irradiation.