Methods of cancer screening utilizing fluorescence detection techniques and selectable imager charge integration periods

• US 6,316,215 B1
• Filed: 06/01/2000
• Issued: 11/13/2001
• Est. Priority Date: 12/27/1999
• Status: Expired due to Fees

• Current Assignee: Micro-Medical Devices, Inc.
• Original Assignee: Micro-Medical Devices, Inc.
• Inventors: Adair, Edwin L., Adair, Randall S., Adair, Jeffrey L.
• Primary Examiner(s): Leary, Louise N.
• Application Number:
  US09/586,768
• Time in Patent Office: 530 Days
• Field of Search: 435/29, 435/968, 435/4
• US Class Current: 435/29
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: H04N 23/54 Mounting of pick-up tubes, electronic image sensors, deviation or focusing coils
• CPC Class Codes: H04N 23/555 for picking-up images in sites, inaccessible due to their dimensions or hazardous conditions, e.g. endoscopes or borescopes
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive

Abstract

The methods of cancer screening allow for a safe, reliable, inexpensive and minimally invasive diagnosis. Cells are first collected through non-invasive or minimally invasive means. The collected cells are stored in a cell culture media. A chemical compound such as 5-ALA is introduced to the cultured cells. The cells are incubated a period of time to allow interaction between the introduced chemical compound and the collected cells. The cells are then studied under a fluorescence microscope which emits a specific frequency of light matching the excitation frequency of fluorescing abnormal cells. Pre-malignant and malignant cells will fluoresce while normal healthy cells generally will not fluoresce. In lieu of or in addition to observing the cells by the fluorescence microscope, an imager may be used to observe the cells wherein the imager includes selectable and variable charge integration capability. Observable fluorescence can be maximized by selecting the appropriate integration period. If necessary, the collected cells may be passed through a flow cytometer to more easily identify the fluorescing cells. A presumptive diagnosis of cancer may be made based upon the presence or absence of fluorescing cells. If a cell sample is adequately concentrated, a cell sorter is not needed, and the cell sample may be adequately viewed under the fluorescence microscope. Specific techniques are disclosed for non-invasive and minimally invasive cell collection. Each of these techniques minimize patient trauma by not requiring forced tissue removal as occurs in traditional biopsy procedures. A method of fluorescence guided endoscopy is also disclosed utilizing an imager with variable charge integration capability.

Claims

1. A method of cancer screening comprising the steps of:

collecting targeted cells from the human body;

placing the collected cells in a cell culture media;

introducing a chemical compound to the collected cells;

maintaining exposure of the collected cells to the chemical compound to allow the collected cells to adequately interact with the chemical compound;

keeping at least some of the collected cells alive during said maintaining step to ensure adequate interaction;

stimulating the collected cells by a selected range of frequency of light to cause pre-malignant and malignant cells to fluoresce;

viewing the collected cells with an imager to determine if fluorescence occurs in the collected cells indicating the presence of cancer; and

adjusting a charge integration period of the imager to maximize observable fluorescence.

2. A method, as claimed in claim 1, further including the step of:

conducting long-term cell observations to further distinguish pre-malignant and malignant cells from normal cells.

3. A method, as claimed in claim 1, further including the step of:

photographing collected cells which fluoresce as documentation for diagnosis of a malignancy.

4. A method, as claimed in claim 1, further including the step of:

conducting flow cytometry to selectively count collected cells.

5. A method, as claimed in claim 1, further including the step of:

conducting fluorescence activated cell sorting to selectively sort collected cells.

6. A method, as claimed in claim 1, wherein:

said chemical compound is 5-ALA.

7. A method of cancer screening achieved by screening cells previously removed from the body, said method comprising the steps of:

placing collected cells in a cell culture media;

introducing a chemical compound to the collected cells;

maintaining exposure of the collected cells to the chemical compound to allow the collected cells to adequately interact with the chemical compound and to keep at least some of the cells alive;

stimulating the collected cells by a selected range of a frequency of light to cause premalignant and malignant cells to fluoresce;

viewing the collected cells with an imager to determine if fluorescence occurs in the collected cells indicating the presence of cancer; and

adjusting a charge integration period of the imager to maximize observable fluorescence.

8. A method, as claimed in claim 7, further including the step of:

conducting long-term cell observations to further distinguish pre-malignant and malignant cells from normal cells.

9. A method, as claimed in claim 7, further including the step of:

photographing collected cells which fluoresce as documentation for diagnosis of a malignancy.

10. A method, as claimed in claim 7, further including the step of:

conducting flow cytometry to selectively count collected cells.

11. A method, as claimed in claim 7, further including the step of:

conducting fluorescence activated cell sorting to selectively sort collected cells.

12. A method, as claimed in claim 7, wherein:

said chemical compound is 5-ALA.

13. A method of cancer screening comprising the steps of:

administering a chemical compound to a patient, said chemical compound being one for use as a fluorescent marker which interacts with a targeted group of cells;

collecting targeted cells from the body;

placing the collected cells in a cell culture media;

maintaining exposure of the collected cells to the chemical compound to further interact with the chemical compound;

keeping at least some of the collected cells alive during said maintaining step to ensure adequate interaction;

stimulating the collected cells by a selected range of a frequency of light to cause premalignant and malignant cells to fluoresce;

viewing the collected cells with an imager to determine if fluorescence occurs in the collected cells indicating the presence of cancer; and

adjusting a charge integration period of the imager to maximize observable fluorescence.

14. A method, as claimed in claim 13, further including the step of:

conducting flow cytometry to selectively count collected cells.

15. A method, as claimed in claim 13, further including the step of:

conducting fluorescence activated cell sorting to selectively sort collected cells.

16. A method of cancer screening comprising the steps of:

administering a chemical compound to a patient, said chemical compound being one for use as a fluorescent marker which interacts with a targeted group of cells;

conducting an endoscopic procedure by use of an endoscope having a variable charge integration imager, to locate the targeted group of cells;

stimulating the targeted group of cells by delivering a selected range of a frequency of light to cause premalignant and malignant cells to fluoresce from the targeted group of cells;

viewing the targeted cells with the imager of the endoscope to determine if fluorescence occurs in the targeted group of cells indicating the presence of cancer; and

adjusting a charge integration period of the imager to maximize observable fluorescence.

17. A method, as claimed in claim 16, wherein:

said chemical compound is 5-ALA.