DE19838232A1 - Micro chip card stores data for a large number of samples to work with a computer through an interface with a large memory and data security - Google Patents

Abstract

The micro chip card, with an electronic memory chip, receives and delivers data through an interface at a computer. The electronic memory chip is a conventional EPROM, E<2>PROM or Flash-EEPROM chip, working in parallel or series through an interface in a computer system. The identification is without the use and arrangement of a database system. An Independent claim is included for the use of the chip card to process large numbers of samples in analysis, biological assay systems, in medical diagnosis and chemical synthesis. Preferred Features: The chip card stores data for coding and identification in parallel and in automated processing of large sample numbers, especially in biology, chemistry and medicine. It stores data for coding and identification of substance libraries of combinatory or solid phase synthesis or paralleled solid phase extraction. It stores data for coding and identification in medical diagnosis.

Description

Especially in the pharmaceutical industry, the field of Active ingredient search and development automation and miniaturization at the Search for new active substances and to optimize lead structures developed by leaps and bounds. In the past few years there has been parallel work enforced as standard in standardized microplates. For example, currently the 96 format in the combinatorial or parallel synthesis of new ones Active substances, for solid phase extractions and in the screening for new ones Active ingredients or used in medical diagnostics. It is expected that with increasing miniaturization the 384 or 1536 plate format will enforce. The high disk allocation leaves the number of data to be managed to soar. So a lot of information, such as Origin, storage of the plates, substance assignment, type of solvent, Information on concentration, substance withdrawal and processing status for a increasing number of samples are processed. When synthesizing additional information such as B. Synthesis conditions, routes (e.g. Pipetting schemes), starting materials and products.

So that data during the automated processing of the microplates in computer controlled synthesis, solid phase extraction, screening or Diagnostic systems can be clearly assigned is a marking of Plates necessary in the course of the process. With today's state of the art Coding the microplates produces a barcode (barcode) that is used to processing plates are printed or glued (EP 5 83 078, DE 43 10 169). With a suitable reader, the barcode of the plate is read and in the Computer network assigned to certain data in databases.

With increasing miniaturization, the amount of data to be processed increases exponentially. The barcode system arrives as active Coding system soon to the limits of information storage. Further Problems with this method are the generation of the bar codes, the pasting of the Microplates, reliable reading, durability in handling and in Storage. Another problem is the development of software that the Barcodes linked to the appropriate data and compatibility with manufactures advanced data processing software. It also has a disadvantage  from that in the processing process of the microplates only with complex active Barcode systems information can be passed on directly to the plate can, which are also very limited in scope.

The invention is therefore based on the object of simple coding of all to enable commercially available microplate systems, being an essential greater information content than stored in the barcode and at the same time one high data security can be guaranteed. The coding should be simple feasible and generally applicable. It's supposed to be in coding choose a data format that is recognized by many computer systems and the data should also be everywhere, for example with portable additional devices, be readable. Furthermore, there should be the possibility of additional process flow resulting data, such as processing times and special Events to store on a microplate. This is supposed to provide complete proof the processing status can be guaranteed. It is said to continue Data transfer independent of an existing data system become.

The object is achieved in that microplates that contain an electronic memory chip are provided. For example, EPROMs, EEPROMs (E ² PROMs), flash EEPROMs or similar memory chips are used as electronic memory chips. The memory chips can, for example, be integrated in the microplate, for example in such a way that the chip is incorporated into the plastic during the manufacture of the microplate, or it is attached, for example, either by means of a fixed connection by means of adhesive (for example by means of synthetic resin, superglue) ) or detachable connections (e.g. double-sided adhesive tape: "Powerstrips" from TESA). The memory chip can be attached at any point on the microplate. This means that all necessary measurements and handling with an automated gripper arm remain unaffected. The electronic memory chips can be unprogrammed or can also contain information and data, such as tables to be supplemented by the user, measurement data and others. Using a computer system and electronic corrosion-resistant contacting (e.g. contact material copper / tin and contact surface gold / nickel), the data is processed in parallel or in series in ASCII (DOS format) or similar data formats such as ANSI (Windows format) or Intel-Hex, written to the memory or read from the chip. The number of contacts depends on the type of memory used. For example, an 8-pin spring contact can be used for serial EEPROMs with a memory capacity of 16 kbit. Alternatively, a PC-controlled contactless read / write device for EEPROMs, for example of the type iID®-2000 from microSensys, can be used, the data being transferred by means of electromagnetic waves. Using the information stored on the memory chip, the microplates can be identified without using and assigning existing database systems.

Accordingly, the invention also relates to the use of the Microplates according to the invention containing electronic memory chips for Processing of large amounts of samples in analytics, in biological Assay systems, in medical diagnostics and chemical synthesis. For example, the application of the new method is used for coding or Identification of microplates in biological assay systems in which medical diagnostics and chemistry. The storage of data on Electronic memory chips are used, for example, for coding and identification of substance libraries in microplate format from the combinatorial or Solid phase synthesis and parallelized solid phase extraction.

The basic structure of the memory chips according to the invention and the use according to the invention is shown schematically in the accompanying Fig. 1.

A lot more information can be stored on a chip than that was previously possible with barcodes. In addition, for example, information saved or changed during the editing process what so far only with cost-intensive and time-consuming active barcode systems was possible. Sharing information directly with the microplate relieves the data network and thus accelerates the whole  Machining process. The evaluation can, for example, at the end of the Machining process.

A great advantage of the invention is that reading and writing to everyone anywhere in the system, d. H. for example in any place where the microplate is turned off, is possible. The transport of the microplate to the reader or the There is no reader for the microplate, as is the case with the barcode. In order to one step in the system is carried out less. Handling becomes safer and Process flow accelerated.

The data, such as measurement data, can be used with minimal hardware expenditure be read and written. The ASCII format used in the example offers the advantage that it can be converted into many software programs without conversion can be imported. This leads to high data security and has a low level Software development effort. For example, the data is also available other systems without a lot of hardware and software.

Depending on the type of memory chips currently available, information from 2 kbit up to 8 Mbit or higher can be saved. With an information content about 64 kBit, the use of parallel memory modules is cheaper because the Writing and reading times at the current state of technology are shorter than with serial working memory chips are. It is possible to save the data on electronic Change memory chips, such as on EEPROM's. The advantage with serial chips is the lower number of necessary electronic contacts. The information stored can be stored on the memory chips without data loss if stored appropriately, be stored safely for at least 10 years

With the application of this new marking technology for microplates, a high density of information can be passed on with the disk. Over a The corresponding interface is, for example, the writing or reading out via Appropriate contacts are possible at any station in the system. With the new coding method, the labeling of the microplate contents independent of existing databases. It results in one significant improvement of storage logistics and coding of Test procedures in microplate format.  

The invention will be explained in more detail using the following exemplary embodiments. Currently, the coding chips are used as read and write devices usual hardware components for programming electronic Memory chips, for example, in connection with an IBM-compatible PC, such as Example of commercially available EPROM programming devices. The electronic Memory chips are commercially available ICs (memory circuits) as a DIP (usual form of housing) or in the form of IC chip cards, for example the TOWITOKO electronics. In principle, all IBM-compatible PCs with RS232 Interface can be used. Alternatively, a PC-controlled contactless one Read / write device for EEPROMs, for example of the type iID®-2000 from microSensys are used, the data transfer using electromagnetic waves occur. As microplates for assay or diagnostic In principle, systems can be used with all standardized plates, such as for example 96 universal plates (Multiwell, from Zinsser, from Greiner). For Applications in solid phase synthesis and extraction can "Microlute" - Plates (Zinsser, Robbins) can be used. The examples are exemplary and do not include all possible applications.

example 1 Data storage on a 2k-E ² PROM (ST24CO2 CP)

A serially organized 2k-E ² PROM (256 × 8 bit) of the type ST24CO2 CP of a chip card (TOWITOKO electronics) was attached by gluing (5-minute epoxy, Conrad Electronic) at a defined location, on the side of C1, attached to a 96-well microplate (from Greiner). Data was written to the memory chip in ASCII format using an 8-pin spring contact made of a copper / tin alloy with a gold / nickel plating on the plate shelf (a perfect match for the glued memory chip). The Chipdrive device (TOWITOKO electronics) was used as a read or write device, and its contacts were connected to those on the disk shelf via an 8-pin cable. The data could be read, changed or supplemented as often as required up to the limit of the memory capacity of 2 kbit.

Example 2 Data storage on a 16k-E ² PROM (24C16)

According to Example 1, a serially organized 16k-E ² PROM of type 24C16 was attached to the side of a 96-well microplate (Greiner) by means of adhesive. Data was written to the memory chip in ASCII format using an appropriate 8-pin contact on the disk storage. The data could be read, changed or supplemented as often as required up to the limit of 16 kBit storage capacity.

The memory chip contained the following information as an example:

Absorbance values of the microplate No. 123456789

Example 3 Data storage on a 64k-E ² PROM (24C64)

According to Example 1, a serially organized 64k-E ² PROM (8k × 8 bit) of the 24C64 type was attached to the side of a 96-well microplate (from Zinsser) by means of adhesive. Data was written to the memory chip in ASCII format using an appropriate 8-pin contact on the disk storage. The data could be read, changed or supplemented as often as required up to the limit of 64 kBit storage capacity.

The memory chip contained the following information as an example:  

Substance assignment of the microplate No. 123456789

Example 4 Data storage on a flash EEPROM (29EE010)

A parallel organized flash EEPROM of type 29EE010 (from Philips) with one Storage capacity of 1 Mbit (128k × 8 bit) was achieved by means of gluing (5-minute Epoxy, from Conrad Electronic) on the side of a 96-well microplate (from Greiner) attached. Via a 32-pin spring contact made of a copper / tin alloy a gold / nickel plating on the plate shelf (fits the glued one Memory chip), data was written to the memory chip in ASCII format. The ELV programmer UP95 (from ELV-Elektronik) served as the read / write device. The data could be read, changed or reached the limit of the number of times Storage capacity can be added.

Example 5 Data storage on an EPROM (27C4001)

According to Example 4, a parallel organized EPROM of the type 27C4001 (from Philips) with a memory capacity of 4 Mbit (512k × 8 bit) attached to the side of a 96-well microplate (from Greiner) by means of adhesive. about an appropriate contact on the plate storage was data in ASCII Format written on the memory chip. The data could be read as often as changed or added to the limit of storage capacity.

Example 6 Data storage on a 64k-E ² PROM (24C64) during synthesis

According to Example 1, a serially organized 64k-E ² PROM (8k × 8 bit) of the type 24C64 was attached to the side of a 96-well "Microlute" plate (from Zinsser) by means of adhesive. Data was written to the memory chip in ASCII format using an appropriate 8-pin contact on the disk storage. The following data (564 bytes) were written to the memory chip as an example during the first synthesis step of a peptide library:

Synthesis No .: 000001 Date: May 18, 1998
Synthetic resin: 2-chlorotrityl
Resin amount: 15 mg loading: 0.91 mmol / g
1. Synthesis step:

• - Coupling of Fmoc amino acids (3 eq)
  A-alanine, B-valine, C-leucine, D-tryptophan,
  E-isoleucine, F-glycine, G-proline, H-vinylalanine
• - reaction conditions:
  Solvent: 0.3 ml CH2Cl2
  Reagents: 0.3 ml DIEA
  Temperature: 20 ° C
  Response time: 6 h
• - Abort reaction:
  Add 0.3 ml CH ₃ OH
  Response time 0.5 h
• - washing steps:
  CH2CL2 3 × 0.5 ml
  CH3OH 3 × 0.5 ml
  Ether 3 × 0.5 ml

Claims (9)

1. microplate containing an electronic memory chip, which by means of a Interface can be written or read out via a computer. 2. Microplate according to claim 1, characterized in that a commercially available, parallel or serial memory chip such as EPROM, E ² PROM or flash EEPROM is used as the electronic memory chip. 3. Microplate according to claim 1, characterized in that information of Memory chips via a serial or parallel interface in a computer system be transmitted. 4. Microplate according to claim 1, characterized in that an identification can be done without using and assigning existing database systems. 5. Use of the microplate according to claim 1 for processing large Sample quantities in analysis, in biological assay systems, in the medical diagnostics and chemical synthesis. 6. Use according to claim 5 for storing data for coding and identification in parallel automated processing of large Sample amounts especially in the fields of biology, chemistry and medicine. 7. Use according to claim 5 for storing data for coding and Identification of substance libraries from the combinatorial or Solid phase synthesis. 8. Use according to claim 5 for storing data for coding and Identification of substance libraries from the parallelized Solid phase extraction. 9. Use according to claim 5 for storing data for coding and Identification in medical diagnostics.